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Allikmets, Rando

Goldman, Jill

Koval, Carrie

Russo, James J. (Jim)

Vundavalli, Murty

Appelbaum, Paul

Greenberg, David

Lee, Joseph H.

Santella, Regina

Warburton Dorothy

Bank, Arthur Hirano, Michio Levy, Brynn Schon, Eric Weissman, Myrna

Chung, Wendy

Hodge, Susan  E.

Marder, Karen

Schupf, Nicole

Williamson Catania, Jennifer

Fraser, Janice

Jobanputra, Vaidehi

Mayeux, Richard

Spitalnik, Steven

 

Frucht, Harold

Karayiorgou, Maria

Ottman, Ruth

Terry, Mary Beth

 

Gharavi, Ali

Karsenty, Gerard

Pirzadeh, Sara

Tsang, Stephen

 

 

   
Researcher Biographical Page

Last name

Allikmets

First name

Rando

Credentials

PhD

Title

Acquavella Associate Professor of Ophthalmology (in Ophthalmology and Pathology & Cell Biology)
Research Director, Dept of Ophthalmology and Harkness Eye Institute

Location of your lab

Eye Institute Research
7th Floor, Room 715
160 Fort Washington Avenue

New York, NY 10032

Location of your clinic

URL of your lab home page:

Researcher picture and lab art:

Rando Allikmets

Research Theme and Projects in your lab:

Genetic cause of Stargardt macular dystrophy and other retinal diseases

ABC transporter superfamily

Association analysis of genetic variation in candidate genes for complex disorders e.g., age-related macular generation

Development of microarray based screening technologies
New approaches for ABC gene therapy.

If you see patients, in which clinic do you attend

Patients are enrolled into our studies at the Harkness Eye Institute

Education and Training Programs to which you belong

Integrated Program
Vision Science Training Grant

Bullet List of Genetic Diseases on which you work:

Age-related macular degeneration
Stargardt diseases
Retinitis pigmentosa
Leber congenital amaurosis
Other retinal diseases

Six Selected Publications (2003-present):

Lamba, J.K., Adachi, M., Sun, D., Tammur, J., Schuetz, E.G., Allikmets, R., and Schuetz, J. Nonsense mediated decay down-regulates conserved alternatively spliced ABCC4 transcript bearing nonsense codons. Hum. Mol. Genet.12:99-109, 2003.

Jaakson, K., Zernant, J., Külm, M., Hutchinson, A., Tonisson, N, Hawlina, M., Ravnic-Glavac, M., Glavac, D., Meltzer, M., Caruso, R., Testa, F., Maugeri, A., Hoyng, C.B., Gouras, P., Simonelli, F., Lewis, R.A. Lupski, J.R., Cremers, F.P.M., and Allikmets, R. Genotyping microarray (gene chip) for the ABCR (ABCA4) gene. Hum. Mutat., 22:395-403, 2003.

Kim, S.R., Fishkin, N., Kong, J., Nakanishi, K., Allikmets, R., and Sparrow, J.R. Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E. Proc. Natl. Acad. Sci. USA, 101:11668-11672, 2004.

Hageman, G.S., Anderson, D.H., Johnson, L.V., Hancox, L.S., Taiber, A.J., Hardisty, L.I., Hageman, J.L., Stockman, H.A., Borchardt, J.D., Gehrs, K.M., Smith, R.J., Silvestri, G., Russell, S.R., Klaver, C.C.W., Barbazetto, I., Chang, S., Yannuzzi, L.A., Barile, G.R., Merriam, J.C., Smith, R.T., Olsh, A.K., Bergeron, J., Zernant, J., Merriam, J.E., Gold, B., Dean, M. and Allikmets R.  A common haplotype in the complement regulatory gene, factor H (HF1/CFH), predisposes individuals to age-related macular degeneration. Proc. Natl. Acad. Sci. USA, 102:7227-7232, 2005.

Maiti, P., Kong, J., Kim, S.R., Sparrow, J.R., Allikmets, R., and Rando, R.R. Small Molecule RPE65 Antagonists Limit the Visual Cycle and Prevent Lipofuscin Formation. Biochemistry, 45:852-860, 2006.

Gold, B., Merriam, J.E., Zernant, J., Hancox, L.S., Taiber, A.J., Gehrs, K.M., Cramer, K., Neel, J., Bergeron, J., Barile, G.R., Smith, R.T., the AMD Genetics Clinical Study Group, Hageman, G.S., Dean, M. and Allikmets R.  Variation in the Factor B (BF) and Complement Component 2 (C2) Genes is Associated with Age-related Macular Degeneration. Nature Genet., 38:458-462, 2006


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Researcher Biographical Page

Last name

Appelbaum

First name

Paul

Credentials

MD

Title

Professor and Director, Division of Psychiatry, Law and Ethics, Department of Psychiatry

Location of your lab
Location of your clinic
URL of your lab home page:

Rm. 6707, NY State Psychiatric Institute

Researcher picture and lab art:

Sent.

Research Theme and Projects in your lab:

Ethical and legal aspects of genetic research and interventions, including informed consent, competence to consent to research and treatment, confidentiality of genetic information, screening for genetic disorders, use of genetic information in legal settings (e.g., claims of reduced culpability because of genetic propensities to engage in criminal behavior).

If you see patients, in which clinic do you attend

Dept. of Psychiatry Faculty Practice
Contact Dr. Appelbaum at 212-543-4184

Education and Training Programs to which you belong

Adult Psychiatry Residency Training
Forensic Psychiatry Fellowship Program

Bullet List of Genetic Diseases on which you work:

Particular interest in behavioral genetics and the genetics of psychiatric and neurological disorders. But interested in ethical and legal issues in all genetic diseases.

Six Selected Publications (2003-present):

Appelbaum PS:  Ethical issues in psychiatric genetics.  Journal of Psychiatric Practice 2004; 10:343-351
Appelbaum PS: Behavioral genetics and the punishment of crime.  Psychiatric Services 2005; 56:25-27
Hoge SK, Appelbaum PS:  Ethical, legal, and social implications of psychiatric genetics and genetic counseling, in Tsuang MT, Smoller JW, Rosen-Sheidley B (eds.):  Psychiatric Genetics:  Applications in Clinical Practice.  American Psychiatric Publishing, Arlington, VA (in press).
Appelbaum PS, Lidz, C:  The therapeutic misconception, in Emanuel EJ, Crouch RA, Grady C, Lie R, Miller F, Wendler D (eds.), The Oxford Textbook of Clinical Research Ethics.  New York, Oxford University Press (in press).
Appelbaum PS, Grisso T:  The MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR).  Professional Resource Press, Sarasota, FL, 2001
Berg JW, Appelbaum PS, Lidz CW, Parker L:  Informed Consent:  Legal Theory and Clinical Practice, 2nd edition.  Oxford University Press, New York NY, 2001.

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Researcher Biographical Page

Last name

Bank

First name

Arthur

Credentials

M.D.

Title

Professor Emeritus of Medicine and of Genetics and Development

Location of your lab
Location of your clinic
URL of your lab home page:

HHSC 1612

Researcher picture and lab art:

Research Theme and Projects in your lab:

The laboratory is funded to develop new methods to do gene therapy for beta thalassemia and sickle cell anemia. This research includes developing new stable packaging lines to do lentiviral globin gene therapy. I am also a co-investigator in an ongoing clinical trial of globin gene therapy underway in Paris, France as part of the sponsor of the trial, Genetix Pharmaceuticals, Inc.
The laboratory is also working on the role of the transcription factors Ikaros and Notch in hematopoiesis.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Thalassemia, sickle cell anemia

Six Selected Publications (2003-present):

Ward, M., Sattler, R., Grossman, I. R., Bell, A. J., Skerrett, D., Baxi, L., and Bank, A.  A stable murine-based RD114 retroviral packaging line efficiently transduces human hematopoietic cells. Molecular Therapy, 8:804-812, 2003.

Bank, A., Dorazio, R. and Leboulch, P. A Phase I/II clinical trial of beta-globin gene therapy for beta-thalassemia. Annals NY Acad Sciences, 1054:308-316,2005.

Bank, A. Understanding globin regulation in beta thalssemia: it’s as simple as alpha, beta, gamma, delta. J. Clin. Invest., 115:1470-3. 2005.

Pulte, D., Lopez, R.A., Baker, S.T., Ward, M., Ritchie, E., Richardson, C.A.’ O’Neill, D.W., and Bank, A. Ikaros increases normal apoptosis in adult erythroid cells. American  J. Hematology, 81:12-18, 2006.

Bank, A. Regulation of human fetal hemoglobin: new players, new complexitites. Blood, 107: 435-43, 2006.

Mantha, S., Ward, M., McCafferty, J., Herron, A., Palomero, T., Ferrando, A., Bank, A., Richardson, C. Activating Notch 1 mutations are an early event in T-cell malignancy of Ikaros point mutant Plastic/+ mice. Leuk. Res, 2006.

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Researcher Biographical Page

Last name

Chung

First name

Wendy

Credentials

MD PhD

Title

Herbert Irving Assistant Professor of Pediatrics and Medicine, Director of Clinical Genetic
Director of the Cytogenetics/Molecular Genetics Fellowship

Location of your lab

1150 St Nicholas Avenue, Room 620

Location of your clinic

Babies Hospital 6 North, 601
Irving Pavilion 1028

URL of your lab home page:

http://www.cumc.columbia.edu/dept/pediatrics/molec/molec.html

Researcher picture and lab art:

Chung, Wendy

Research Theme and Projects in your lab:

A major focus of our research is in the molecular genetics of obesity in humans with increased emphasis on computational analysis of gene by gene interactions. As part of the project we recently created a mouse carrying a human gene variant in the leptin receptor that has been associated with excess body fat. We are studying the ingestive behavior and energy expenditure of this mouse. A second project is designed to clone modifier genes for type 2 diabetes from obese mice. We have identified a candidate gene of unknown function whose hypoactivity causes reduced beta cell mass. The molecular physiology of this gene is being pursued in a knockout mice.

As the molecular genetics core laboratory for studies in the Pediatric Heart Network, we are identifying genetic factors modulating disease severity of congenital heart disease.  We are also studying genetic polymorphisms that determine the rate of progression for cardiomyopathy and pulmonary hypertension. We are characterizing the genetic causes of cardiomyopathy and arrhythmias and are developing novel methods of high throughput screening for gene panels.  We are clinically and genomically characterizing children with congenital heart disease and congenital diaphragmatic hernias for copy number changes in the germline. 

As the molecular genetics core for the Pediatric Neuromuscular Clinical Research Network, we work with an established clinical research network that clinically and molecularly characterizes patients with spinal muscular atrophy and is preparating for SMA clinical trials.

We are identifying novel genes for breast cancer susceptibility through the Breast Cancer Family Registry and attempting to identify genetic modifiers of the breast cancer susceptibility genes BRCA1 or BRCA2.

If you see patients, in which clinic do you attend

Pediatrics
Prenatal
Cardiovascular Genetics
Muscular dystrophy clinic
Cancer genetics
Von Hippel Lindau
Cystic fibrosis
Vascular anomalies
212-305-6731
See website for further details http://www.cumc.columbia.edu/dept/pediatrics/clin/intro.html

Education and Training Programs to which you belong

Cardiovascular Development and Disease in the Young
Multidisciplinary Training in Translational Cardiovascular Research
Training Grant in Neonatal-Perinatal Medicine
Training Grant in Pharmacological Sciences
MD/PhD Training Grant
Director of the Cytogenetics and Molecular Genetics Fellowship
Faculty member for the Medical Genetics Residency
Section chief, Genetics for SBMP medical student course

Bullet List of Genetic Diseases on which you work:

Obesity
Diabetes
Cardiomyopathies
Congenital heart disease
Arrhythmias
Breast cancer
Spinal muscular atrophy
Birth defects
Congenital diaphragmatic hernias

Six Selected Publications (2003-present):

Jobanputra V, Sebat J, Troge J, Chung W, Anyane-Yeboa K, Wigler M, Warburton D.  Application of ROMA (representational oligonucleotide microarray analysis) to patients with cytogenetic rearrangements. Genet Med. 2005 Feb;7(2):111-8.

Sun, L., Eklund, E. A., Chung. W. K., Cohen, J., and Freeze. H.,  Congenital Disorder of Glycosylation Id (CDG-Id) Presenting with Hyperinsulinemic Hypoglycemia and Islet Cell Hyperplasia. J Clin Endocrinol Metab. 90(7):4371-5, 2005.

Matsuoka, N., Patki, A., Tiwari, H.K., Allison, D.B., Johnson, S.B., Gregersen, P.K.,Leibel, R.L., and Chung, W.K. Association of K121Q Polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American Adults.  International Journal of Obesity. Oct 11 2005.

Codner, E., Deng, L., Pérez-Bravo, F., Román, R., Lanzano, P.,

Cassorla, F., and  Chung, W.K., Glucokinase mutations in young children with hyperglycemia.  Diabetes and Metabolism Research and Reviews.  Jan 30 2006; Epub.

Phan, L. K., Chung, W. K., Leibel, R. L., The Mahoganoid mutation (Mgrn1md) improves insulin sensitivity in mice with mutations in the melanocortin signaling pathway independent of effects on adiposity.  American Journal of Physiology.  In press.

Tierney, E. S., Marans, Z, Rutkin, M.B. , Chung, W.K. CRYPTIC (CFC1) Variants in Laterality Defects Associated with Congenital Heart Disease.  Cardiology in the Young, Accepted. 

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Researcher Biographical Page

Last name

Fraser

First name

Janice

Credentials

MS, CGC

Title

Genetic Counselor/Research Coordinator

Location of your lab

Location of your clinic

Neurological Institute, 3rd floor

URL of your lab home page:

http://www.movement-disorders.org/genetic.html

Researcher picture and lab art:

Research Theme and Projects in your lab:

Genetics of Movement Disorders
Consortium On Risk for Early-onset PD (COREPD)
Beta-glucocerebrosidase mutations and PD in the Ashkenazim

If you see patients, in which clinic do you attend

Movement Disorders, Neurological Institute 3rd floor

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Parkinson’s Disease
Dystonias
Spinocerebellar Ataxias

Six Selected Publications (2003-present):

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Researcher Biographical Page

Last name

Frucht

First name

Harold

Credentials

MD

Title

Associate Professor of Clinical Medicine

Location of your lab

Location of your clinic

Herbert Irving (Atchley) Pavilion, Suite #301

URL of your lab home page:

http://www.columbiasurgery.org/pat/pancreas/prevention.html
http://www.cumc.columbia.edu/dept/gi/colonca.html

Researcher picture and lab art:

Research Theme and Projects in your lab:

Syndromic Gastrointestinal Cancers:

Genetic counseling & testing, risk-stratification, and early detection & prevention of gastrointestinal cancers including colon cancer and pancreas cancer.

If you see patients, in which clinic do you attend

Gastrointestinal High Risk/Genetics/Screening Program
Digestive Diseases Division Clinical Office
(212) 305-1021 or (212) 305-5333

Education and Training Programs to which you belong

As above

Bullet List of Genetic Diseases on which you work:

- familial polyposis coli (175100, 276300)
- familial juvenile polyposis (174900)
- hereditary non-polyposis colon cancer (120435, 609310, 158320, 114400, 13725)
- familial pancreatic cancer (260350)
- familial atypical multiple melanoma mole syndrome (606719)
- peutz-jeghers syndrome (175200)
- hereditary pancreatitis (167800)
- BRCA syndrome (113705, 600185)
- multiple endocrine neoplasia type I syndrome (131100)

Six Selected Publications (2003-present):

Calvert P, Frucht H. The genetics of colorectal cancer. Annals of Internal Medicine. 2002; 137:603-612.

Frucht H, Stevens PD, Fogelman DR, Verna EC, Chen J, Chabot JA, Fine RL. Advances in the Genetic Screening, Work-up, and Treatment of Pancreatic Cancer. Current Treatment Options in Gastroenterology.  2004; 7:343-354.


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Researcher Biographical Page

Last name

Gharavi

First name

Ali

Credentials

1986:  B.S. Georgetown Univ.
1990: M.D. George Washington Univ.
1990-93: Intern and Resident in Medicine, Mount Sinai Medical CenterNew York, NY
1996-98: Fellow in Nephrology, Mount Sinai Medical Center, NY
1997-2002 : Yale University, Post Doc in Genetics

Title

Assistant Professor of Medicine

Location of your lab

P&S 10-432

Location of your clinic

URL of your lab home page:

Researcher picture and lab art:

Research Theme and Projects in your lab:

End-stage renal disease requiring dialysis therapy affects one in a seven hundred Americans. The molecular bases of renal failure are largely unknown but multiple lines of evidence suggest that genetic susceptibility is an important causative factor.  We are interested in several disorders that  result in renal failure:

1- IgA nephropathy (IgAN, OMIM #161950) is the most common form of glomerulonephritis and a significant cause of renal failure worldwide.  This trait has complex determination.  Starting with a collection of kindreds with familial disease, we have mapped the first locus for IgA nephropathy to chromosome 6q22-23 and our efforts are now geared towards identifying the underlying genes using approaches such as disequilibrium mapping and sequencing of positional candidates. In addition, mapping projects in newer families and case-control cohort recruited worldwide are expected to identify additional loci and variants responsible for IgA nephropathy.

2- Nonsyndromic defects in the urinary tract are the most common cause of end-stage renal failure in children. Renal agenesis (OMIM %191830) is one of the most severe forms of malformations and is also commonly accompanied by anatomic abnormalities in the lower urinary tract such as ureteropelvic junction (UPJ) obstruction or vesicoureteral reflux (VUR %193000).  The genetic basis of these disorders is not known.  We are studying cohorts segregating renal agenesis or VUR in order to identify genes and variants predisposing to these traits.

If you see patients, in which clinic do you attend

Nephrology
212-305-0320

Education and Training Programs to which you belong

Cardiology training program, Columbia University
Nephrology Training program (Mt Sinai School of Medicine)

Bullet List of Genetic Diseases on which you work:

  • IgA nephropathy
  • HIV nephropathy
  • Vesicoureteral Reflux
  • Renal agenesis and Renal Developmental Defects

Six Selected Publications (2003-present):

1. Gharavi AG, Ahmad T, Wong RD, Hooshyar R, Vaughn J, Oller S, Frankel RZ , Bruggeman LA , D'Agati VD , Klotman PE , and Lifton RP. Mapping a Locus (HIVAN1) for Susceptibility to HIV-1 Associated Nephropathy to Mouse Chromosome 3. Proc Natl Acad Sci U S A.  2004, 101:2488-2493

2. Davila S., Furu L., Gharavi AG, Tian X., Onoe T., Qian Q, Li A., Kamath PS, King BF, Azurmendi PJ, Tahvanainen, Kääriäinen H, Höckerstedt K, Devuyst O, Pirson Y, Martin R, Lifton R, Tahvanainen E, Torres V, Somlo S. Mutations in SEC63 cause autosomal dominant polycystic liver disease and implicate posttranslational modification pathways in epithelial cyst formation. Nat. Genetics 2004, 36:575-7

3. Zheng Z,  Ott-Schmitt K, Chua S., Foster K A., Frankel R Z., Barasch J,  Pavlidis P., D’ Agati VD, Gharavi AG.  A Mendelian Locus on Chromosome 16 Determines Susceptibility to Doxorubicin Nephropathy In The Mouse. Proc Natl Acad Sci U S A.  2005;102:2502-2507

4. Sanna-Cherchi S, Reese A, Hensle T, Caridi G, Izzi C, KimYY, Murer L, Scolari F, Ravazzolo R, Ghiggeri GM, Gharavi AG.  Familial Vesicoureteral Reflux:  Testing Replication of Linkage in Seven New Multigenerational Kindreds.  J Am Soc Nephrol 2005;16:1781-7

5. C Izzi, S Sanna-Cherchi, E Prati, D Beller , A Remedi , R Tardanic , M Foramitt , S Guerini, B Viol , G Brunori, E Movilli, I Beerman, R Lifton, P Paterlini, C Della Torre, L Leone, Gharavi AG, Scolari F. Familial Aggregation of Primary Glomerulonephritis in an Italian Population Isolate: the Valtrompia Study. Kidney International 2006 69:1033-40


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Researcher Biographical Page

Last name

Greenberg

First name

David A.

Credentials

Ph.D., Physiology and Biochemistry, Washington University, St. Louis, MO, 1976

Title

Director, Division of Statistical Genetics; Professor, Departments of Biostatistics and Psychiatry;

Location of your lab

(Office) 722 West 168th Street, Room 623

Location of your clinic

URL of your lab home page:

“Division of Statistical Genetics” Web page is currently being developed.

Researcher picture and lab art:

David Greenberg

Research Theme and Projects in your lab:

“A Multicenter Study of Idiopathic Generalized Epilepsy”
This grant has four goals: 1) Determine the sequence differences in the malic enzyme 2 gene (ME2) that cause the association of ME2 with idiopathic generalized epilepsy. 2) Locate the genes within the areas of high linkage on chromosomes 5 and 8. 3) Determine if the ME2 and BRD2 genes, both of which are associated with JME, interact. 4) Determine whether the associations we have identified in the Caucasian population can also be found in the African American and Hispanic populations. The last aim is critical for understanding how the causes of IGE may differ in different ethnic groups.
Principal Investigator: David A. Greenberg
.Agency: NIH-NINDS
Type: RO1 NS027941. Years 17 – 21.
Period: 8/15/2006 – 1/31/2011

“Two-Locus Models, Heterogeneity and Diabetes”
The major goal of this project is to use computer simulation to investigate problems in the analysis of human genetic data and develop new analysis methods.
Principal Investigator: David A. Greenberg
Agency: NIH-NIDDK
Type RO1 DK031775, Years 20 – 24.
Period: April 1, 2003 – February 28, 2007

“Search for Genes Influencing Childhood Absence Epilepsy”
The major goal of this project is performing genome screens on childhood absence families.
Principal Investigator: Martina Durner
Agency: NIH –NINDS
Type: RO1 NS037466, Years 1-5.
Period: June 1, 2006 to May 31, 2011.

“Genetics of Rolandic Epilepsy”
The goal is to find the susceptibility genes underlying rolandic epilepsy and its component EEG and neurodevelopmental traits.
Principal Investigator – Deb Pal, M.D.
Agency:NIH-NINDS
Type: RO1 NS047530-01
Period: January 15, 2005 to January 14, 2009

“Mapping Autoimmune Diabetes and Thyroiditis Genes”
The goal is to determine genes common to expression of Type 1 Diabetes and Autoimmune Thyroid Disease.
Subcontract from University of Cincinnati, Principal Investigator – David A. Greenberg, Ph.D.
Agency NIH
Type: DK067555-01A1
Period: January 31, 2005 to January 30, 2009

“Schizophrenia Premorbid Endophenotype”
The major goal of this project is to investigate the inheritance of schizophrenia
Subcontract from Mt. Sinai Medical Center,
.Principal Investigator – David A. Greenberg, Ph.D.
Agency NIH/NIMH –
Type: RO1 MH066105
Period: March 1, 2006 – February 28, 2009

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Co-Principal Investigator on “Genetic Analysis: Psychiatric and Other Complex Diseases,” The Genetics of Complex Disorders (GCD) training program.  NIMH T32 Training Grant, 2002–2007 (renewal submitted).

Co-director of Division of Statistical Genetics, in Dept. of Biostatistics, School of Public Health (Dr. David A. Greenberg, Director).

Also supervise the new Master’s track in Statistical Genetics, in Dept. of Biostatistics, School of Public Health.

Mathematical Genetics Unit in Dept. of Psychiatry (in Dr. Myrna Weissman’s Clinical-Genetic Epidemiology Unit)

Bullet List of Genetic Diseases on which you work:

  • Idiopathic Generalized Epilepsy
  • Autoimmune Thyroid Disease
  • Schizophrenia
  • Diabetes

Six Selected Publications (2003-present):

Greenberg DA, Durner, M, Keddache, M, Shinnar et al (2000) Reproduceability and Complications in Gene Searches: Linkage, Heterogeneity, Association, and Inheritance in Juvenile Myoclonic Epilepsy. Am J Hum Genet 66:508-516.

Durner M, Keddache M, Shinnar SS, Resor SR, Cohen J, Harden C, Moshe S.L, Rosenbaum D, Kang H, Ballaban-Gil K, Hertz S, Labar DR, Luciano D, Wallace S, Yohai D, Klotz I, Dicker E, Greenberg DA (2001): Genome scan of idiopathic Generalized epilepsy: Evidence for major susceptibility gene and modifying genes influencing seizure type. Annals of Neurology.49:328-335.

Greenberg DA, Abreu P (2001): Determining trait locus position from multipoint analysis: accuracy and power of three different statistics. Genetic Epidemiology 21:299-314.

Pal DK, Evgrafov OV, Tabares P, Zhang F, Durner M, Greenberg DA (2003): BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy. Am J Hum Genet. 73:261-70.

Heiman G, Hodge S.E, Goroochurn P, Zhang J, Greenberg DA (2004): Effect of population stratification on case- control association studies: I. Elevation in false positive rates and comparison to confounding risk ratios (a simulation study). Hum Hered. 58:30-39.

Greenberg DA, Cayanis E, Strug,et al (2005): Malic Enzyme 2 may underlie susceptibility to adolescent-onset idiopathic generalized epilepsy. Am J Hum Genet. 76:139–146


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Researcher Biographical Page

Last name

Goldman

First name

Jill

Credentials

MS, MPhil, CGC

Title

Senior Staff Associate, Genetic Counselor

Location of your lab

Sergievsky Center, Taub Institute

Location of your clinic

630 W. 168th St, 19th floor

URL of your lab home page:

http://www.alzheimercenter.org

Researcher picture and lab art:

Goldman Jill

Research Theme and Projects in your lab:

If you see patients, in which clinic do you attend

We see patients who are at risk for hereditary dementia including, Alzheimer disease, Huntington disease, Frontotemporal dementia, Prion disease.
Patients should contact me at 212-305-7382

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Alzheimer disease
Frontotemporal dementia and related diseases
Prion disease
Other hereditary dementias such as CADASIL

Six Selected Publications (2003-present):

Goldman JS, Farmer JM, Wood EM, Johnson JK, Boxer A, Neuhaus J, Lomen-Hoerth C, Wilhelmsen KC, Lee VM, Grossman M, Miller BL. Comparison of family histories in FTLD subtypes and related tauopathies. Neurology. 2005 Dec 13;65(11):1817-9

Goldman JS, Johnson JK, McElligott K, Suchowersky O, Miller BL, Van Deerlin VM. Presenilin 1 Glu318Gly polymorphism: interpret with caution. Arch Neurol. 2005 Oct;62(10):1624-7.

Goldman JS, Farmer JM, Van Deerlin VM, Wilhelmsen KC, Miller BL, Grossman M. Frontotemporal dementia: genetics and genetic counseling dilemmas. Neurologist. 2004 Sep;10(5):227-34.

Goldman JS, Miller BL, Safar J, de Tourreil S, Martindale JL, Prusiner SB, Geschwind MD. When sporadic disease is not sporadic: the potential for genetic etiology. Arch Neurol. 2004 Feb;61(2):213-6.

Goldman JS, Reed B, Gearhart R, Kramer JH, Miller BL. Very early-onset familial Alzheimer's disease: a novel presenilin 1 mutation. Int J Geriatr Psychiatry. 2002 Jul;17(7):649-5.

Wilhelmsen KC, Forman MS, Rosen HJ, Alving LI, Goldman J, Feiger J, Lee JV, Segall SK, Kramer JH, Lomen-Hoerth C, Rankin KP, Johnson J, Feiler HS, Weiner MW, Lee VM, Trojanowski JQ, Miller BL. 17q-linked frontotemporal dementia-amyotrophic lateral sclerosis without tau mutations with tau and alpha-synuclein inclusions.
Arch Neurol. 2004 Mar;61(3):398-406.

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Researcher Biographical Page

Last name

Hirano

First name

Michio

Credentials

MD
Adult neurologist

Title

Associate Professor

Location of your lab

P&S 4-443

Location of your clinic

Neurological Institute of New York, 9th Floor

URL of your lab home page:

Researcher picture and lab art:

Research Theme and Projects in your lab:

My laboratory is part of the H. Houston Merritt Clinical Research Center. We study neuromuscular and mitochondrial diseases. We have identified causative genes for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), Danon disease, and coenzyme Q10 deficiency. We are exploring the pathogenesis and treatments for MNGIE and coenzyme Q10 deficiency and hunting for genes causing scapuloperoneal muscular dystrophy and limb-girdle muscular dystrophy 1F.

If you see patients, in which clinic do you attend

Dr. Hirano is the Co-Director of the Muscular Dystrophy Association Clinic at Columbia University.

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), OMIM 603041
Coenzyme Q10 deficiency, OMIM 607426
Scapuloperoneal muscular dystrophy, OMIM 181430
Limb girdle muscular dystrophy 1F, OMIM 608423

Six Selected Publications (2003-present):

Nishigaki Y, Martí R, Copeland WC, Hirano M (2003) Site-specific mtDNA point mutations due to thymidine phosphorylase deficiency. J Clin Invest 111:1913-1921

Palenzuela L, Andreu AL, Gamez J, Vilà MR, Kunimatsu T, Meseguer A, Cervera C, Fernandez Cadenas I, Van Der Ven PF, Nygaard TG, Bonilla E, Hirano M (2003) A novel autosomal dominant limb-girdle muscular dystrophy (LGMD 1F) maps to 7q32.1-32.2. Neurology 61:404-406

Quinzii CM, Kattah AG, Naini A, Akman HO, Mootha VK, DiMauro S, Hirano M (2005) Coenzyme Q deficiency and cerebellar ataxia associated with an aprataxin mutation. Neurology 64:539-541

Quinzii C, Naini A, Salviati L, Trevisson E, Navas P, DiMauro S, Hirano M (2006) A Mutation in Para-Hydroxybenzoate-Polyprenyl Transferase (COQ2) Causes Primary Coenzyme Q10 Deficiency. Am J Hum Genet 78:345-349

Karadimas CL, Vu TH, Holve SA, Chronopoulou P, Quinzii C, Johnsen SD, Kurth J, Eggers E, Palenzuela L, Tanji K, Bonilla E, De Vivo DC, DiMauro S, Hirano M (2006) Navajo Neurohepatopathy Is Caused by a Mutation in the MPV17 Gene. Am J Hum Genet 79:544-548

Hirano M, Martí R, Casali C, Tadesse S, Uldrick T, Fine B, Escolar DM, Valentino ML, Nishino I, Hesdorffer C, Schwartz J, Hawks RG, Martone DL, Cairo MS, DiMauro S, Stanzani M, Garvin JH, Savage DG (2006) Allogeneic stem cell transplantation corrects biochemical derangements in MNGIE. Neurology in press

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Researcher Biographical Page

Last name

Hodge

First name

Susan  E.

Credentials

D.Sc., Applied Mathematics & Computer Science, Washington University, St. Louis, MO, 1976.

Title

Professor of Clinical Biostatistics (in Psychiatry)

Location of your lab

Location of your clinic

Office: Room 117, Kolb Annex of NYSPI (NY State Psychiatric Institute)

URL of your lab home page:

“Division of Statistical Genetics” Web page is currently being developed.

Researcher picture and lab art:

Susan Hodge

Research Theme and Projects in your lab:

Statistical methodology in genetic epidemiology; also mathematical modeling.  Examples: methods of linkage analysis; methods of association analysis; dealing with population stratification in association analysis; testing for and incorporating genetic heterogeneity; issues of “multiple testing”;  etc.
Current research grants on which Dr. Hodge is P.I.:
“Linkage and Association in Complex Genetic Diseases.”  NIH, 1983–2008.
“Psychiatric Genetics and Family Studies: Robust Methods.”  NIMH, 1992–2010.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Principal Investigator on “Genetic Analysis: Psychiatric and Other Complex Diseases,” The Genetics of Complex Disorders (GCD) training program.  NIMH T32 Training Grant, 2002–2007 (renewal submitted).

Co-director of Division of Statistical Genetics, in Dept. of Biostatistics, School of Public Health(Dr. David A. Greenberg, Director).

Also supervise the new Master’s track in Statistical Genetics, in Dept. of Biostatistics, School of Public Health.

Mathematical Genetics Unit in Dept. of Psychiatry (in Dr. Myrna Weissman’s Clinical-Genetic Epidemiology Unit)

Member of PET (Psychiatic Epi Training program)

Bullet List of Genetic Diseases on which you work:

Panic disorder
A genetic study of fear and anxiety

Six Selected Publications (2003-present):

Hamilton, S.P., Fyer, A.J., Durner, M., Heiman, G.A., de Leon, A.B., Hodge, S.E., Knowles, J.A. & Weissman, M.M. Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q. PNAS 100: 2550–2555, 2003.

Spence, M.A., Greenberg, D.A., Hodge, S.E. & Vieland, V.J. The Emperor’s new methods. Invited Editorial. Am J Hum Genet 72: 1084–1087, 2003.

Lindholm, E., Zhang, J., Hodge, S.E. & Greenberg, D.A. The reliability of haplotyping inference in nuclear families: Misassignment rates for SNPs and microsatellites.  Hum Hered 57: 117–127, 2004.

Heiman, G.A., Hodge, S.E., Gorroochurn, P., Zhang, J. & Greenberg, D.A. Effect of population stratification on false positive rates in association analysis. I. Elevation in false positive rates and comparison to confounding risk ratios (a simulation study). Hum Hered 58:30–39, 2004.

Gorroochurn, P., Hodge, S.E., Heiman, G. & Greenberg, D.A. Effect of population stratification on case-control association studies. II. False-positive rates and their limiting behavior as the number of subpopulations increases. Hum Hered 58: 40–48, 2004.

Strug, L.J & Hodge, S.E. An alternative foundation for the planning and evaluation of linkage analysis. I. Decoupling “error probabilities” from “measures of evidence.” Hum Hered 61: 166–188, 2006.

Strug, L.J. & Hodge, S.E. An alternative foundation for the planning and evaluation of linkage analysis. II. Implications for multiple test adjustments. Hum Hered, in press.

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Researcher Biographical Page

Last name

Jobanputra

First name

Vaidehi

Credentials

Ph.D. ABMG certified in Clinical Cytogenetics

Title

Assistant Professor of Clinical Pathology

Location of your lab

Cytogenetics Laboratory, CHC - 406

Location of your clinic

vj2004@columbia.edu

Researcher picture and lab art:

Vaidehi Jobanputra

Research Theme and Projects in your lab:

I am interested in studying constitutional chromosomal disorders. In collaboration with Dorothy Warburton and the Wigler Lab at Cold Spring Harbor Laboratory we have previously demonstrated the accuracy and sensitivity of ROMA (Representational Oligonucleotide Microarray Analysis) to describe copy number changes in patients with known chromosomal abnormalities. This analysis has served to illustrate the resolution with which we can define chromosomal imbalances. We are now applying this approach to study genomic copy number changes in children with congenital heart defects.

More recently with Brynn Levy we are accessing the utility of SOMA (SNP Oligonucleotide Microarray Analysis) for clinical cytogenetic diagnosis. We are analyzing copy number changes in patients with previously known and unknown constitutional structural chromosome rearrangements. This information should immensely improve our ability both to understand the mechanisms of chromosomal rearrangements and to provide more accurate prognosis both prenatally and postnatally to parents of offspring with chromosomal aberrations.

Another focus of our research is to understand the factors contributing to nondisjunction in ageing human oocytes. Advanced maternal age is the only established risk factor for trisomy, the most frequent known cause of embryonic death and a major cause of severe mental retardation. Genetic studies suggest that the error arises principally during meiosis I of the oocyte both for trisomy 21 births (Down syndrome) and for trisomies among spontaneous abortions. We are studying meiotic proteins affecting chromosome segregation in oocytes from women of different age groups.

If you see patients, in which clinic do you attend

Division of Clinical Genetics, Department of Pediatrics.

Education and Training Programs to which you belong

ABMG training program in Clinical Cytogenetics and Molecular Genetics.

Bullet List of Genetic Diseases on which you work:

Constitutional chromosomal disorders
Congenital Heart Disease

Six Selected Publications (2003-present):

1. Jobanputra V, Sobrino A, Kinney A, Kline J, Warburton D. Multiplex interphase FISH as a screen for common aneuploidies in spontaneous abortions. Hum Reprod (2002) 17(5):1166-1170.

2. Jobanputra V, Sebat J, Troge J , Chung W, Yeboa KA, Wigler M, Warburton D. Application of ROMA (Representational oligonucleotide Microarray Analysis) to Patients with Cytogenetic Rearrangements. Genetics In Medicine (2005) 7(2) 111-118.

3. Jobanputra V, Chung W, Hacker A.M., Emanuel B.S., Warburton D. A unique case of der(11)t(11;22),-22 arising from 3:1 segregation of a maternal t(11;22) in a family with co-segregation of the translocation and breast cancer. Prenatal Diagnosis (2005) 25(8):683-686.

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Researcher Biographical Page

Last name

Karayiorgou

First name

Maria

Credentials

M.D.

Title

Professor

Location of your lab

1051 Riverside Drive, Room 5917

Location of your clinic

URL of your lab home page:

Under construction

Researcher picture and lab art:

Research Theme and Projects in your lab:

My laboratory works on the genetic causes of major psychiatric illness. Our main focus is on schizophrenia (SCZ), a complex psychiatric disorder that affects ~1% of the population world-wide. Our research is multi-faceted and utilizes a number of cutting-edge technologies, including genome-wide association studies, generation of sophisticated genetic mouse models and evaluation of quantitative phenotypes in patients.

Our current active projects include:

1. Identification of SCZ-susceptibility genetic loci through linkage and genome-wide association studies in an exclusive sample of multiplex families we have collected from the genetically isolated Afrikaner population. In this sample, in collaboration with Dr. Abecasis at Michigan, we have already identified strong disease susceptibility loci on chromosomes 1 and 13, which we have fine-mapped through extensive SNP genotyping to a few kilobases candidate intervals. Our current efforts focus on further fine-mapping and re-sequencing of resident genes for identification of disease-associated variants.

2. Detailed studies of biological function of risk haplotypes and risk genetic variants identified in SCZ patients, as well as generation and evaluation of reliable animal models for strong susceptibility genes identified directly through human mapping studies. We are particularly interested in deciphering common mechanisms of action and interaction among susceptibility genes (collaboration with Dr. Gogos’ lab at the Dept of Physiology).

3. Identification of early pre-morbid SCZ risk factors through a clinical/genetic program where a cohort of children with 22q11 microdeletions (the highest known genomic risk factor for schizophrenia) are being evaluated annually and followed longitudinally.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

• Schizophrenia

• 22q11 deletion syndrome (a.k.a. VCFS)

Six Selected Publications (2003-present):

Service S, DeYoung J, Karayiorgou M, Roos JL, Pretorious H, Bedoya G, Ospina J, Ruiz-Linares A, Macedo A, Palha JA, Heutink P, Aulchenko Y, Oostra B, van Duijn C, Jarvelin MR, Varilo T, Peddle L, Rahman P, Piras G, Monne M, Murray S, Galver L, Peltonen L, Sabatti C, Collins A, Freimer N. Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies. Nat Genet 38(5):556-60. (2006) 

Paterlini M, Zakharenko SS, Lai WS, Qin J, Zhang H, Mukai J, Westphal KG, Olivier B, Sulzer D, Pavlidis P, Siegelbaum SA, Karayiorgou M, Gogos JA.           Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice. Nat Neurosci 8(11):1586-94. (2005)

Sobin C, Kiley-Brabeck K, Karayiorgou M.     Lower prepulse inhibition in children with the 22q11 deletion syndrome.  Am J Psychiatry 162(6):1090-9. (2005)

Mukai J, Liu H, Burt RA, Swor DE, Lai WS, Karayiorgou M, Gogos JA. Evidence that the gene encoding ZDHHC8 contributes to the risk of schizophrenia. Nat Genet 36(7):725-31. (2004)

Abecasis GR, Burt RA, Hall D, Bochum S, Doheny KF, Lundy SL, Torrington M, Roos JL, Gogos JA, Karayiorgou M. Genomewide scan in families with schizophrenia from the founder population of Afrikaners reveals evidence for linkage and uniparental disomy on chromosome 1. Am J Hum Genet 74(3):403-17. (2004)

Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA. Convergent evidence for impaired AKT1-GSK3beta signaling in schizophrenia. Nat Genet 36(2):131-7. (2004)

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Researcher Biographical Page

Last name

Karsenty

First name

Gerard

Credentials

Title

Location of your lab

16th Floor of the Hammer Building

Location of your clinic

URL of your lab home page:

Researcher picture and lab art:

Karsenty Gerar

Research Theme and Projects in your lab:

Research in my laboratory aims at elucidating the genetic bases of bone development and functions with the long-term goal to impact on the treatment of genetic and degenerative diseases of the skeleton. To acheive these two complementary aims we most often used human genetic information to define and then test in mice novel hypotheses. In term of bone development we are at the present time studying the role of an osteoblast-specific transcription factor, AFT4, in the pathogenesis of two genetic diseases and exploiting knowledge about its molecular mode of action to devise therapeutic approaches for these two diseases. In terms of bone physiology we are asking two distinct questions. The first one is to delineate the genetic pathway regulating each function of the skeleton with the goal to identify entry point for more rationale treatments of bone degenerative diseases such as osteoporosis. The second one is to use a purely genetic approach to identify novel functions of the skeleton as a regulator of other organs physiology.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Genetics & Development, Integrated Program, and Biochemistry

Bullet List of Genetic Diseases on which you work:

Coffin-Lowry Syndrome
Cleido-Cranial Dysplasia
Neurofibromatosis

Six Selected Publications (2003-present):

1. Kim S, Koga T, Isobe M, Kern BE, Yokochi T, Chin YE, Karsenty G, Taniguchi T and Takayanagi H.: Stat1 functions as a cytoplasmic attenuator of Runx2 in the transcriptional program of osteoblast differentiation. Genes Dev.17:1979-91, 2003.

2. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, Wu H, Yu K, Ornitz D, Olson E Justice M and Karsenty G.: A Twist code determines the onset of osteoblast differentiation. Developmental Cell, 6: 423-435, 2004.

3.Yang X, Matsuda K, Bialek P, Jacquot S, Masuoka H, Schinke T, Li L, Townes T, Hanauer A and Karsenty G: ATF4 is a substrate of RSK2 and an essential regulator of osteoblast biology: implication for Coffin-Lowry Syndrome. Cell, 117: 3870-398, 2004.

4. Vega RB, Matsuda K, Oh J, Barbosa AC, Yang X, Meadows E, McAnally J, Pomajzl C, Shelton JM, Richardson JA, Karsenty G and Olson EN: Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell 12;119: 555-66, 2004.

5. Elefteriou F, Ahn JD, Takeda S, Starbuck M, Yang X, Liu X, Kondo H, Richards WG, Bannon TW, Noda M, Clement K, Vaisse C and Karsenty G.: Leptin regulation of bone resorption via the sympathetic nervous system and CART. Nature 434:514-20, 2005.

6. Glass DA, Bialek P, Ahn, JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA and Karsenty G: Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 5: 751-64, 2005

7. Murshed M, Harmey D, Millan JL, McKee MD and Karsenty G: Unique co-expression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone. Genes Dev 19:1093-1104, 2005.

8. Fu L, Patel MS, Bradley A, Wagner EF and Karsenty G: The molecular clock mediates leptin-dependent regulation of bone formation. Cell 122(5):803-15, 2005.

9. Dobreva G, Chahrour M, Dautzenberg M, Chirivella L, Kanzler B, Farinas I, Karsenty G and Grosschedl R: SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell 125(5):971-86, 2006.

Winslow M, Pan M, Starbuck M, Gallo E, Deng L, Karsenty G and Crabtree G: Calcineurin/NFAT Signaling in Osteoblasts Regulates Bone Mass. Dev Cell Jun; 10(6):771-82, 2006.


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Researcher Biographical Page

Last name

Koval

First name

Carrie

Credentials

M.S.

Title

Genetic Counselor

Location of your lab

16th Floor of the Hammer Building

Location of your clinic

Children’s Hospital, 6 North, rm 601A

URL of your lab home page:

Researcher picture and lab art:

Research Theme and Projects in your lab:

If you see patients, in which clinic do you attend

Prenatal, Pediatrics, Pediatric and Adult Neuromuscular

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Six Selected Publications (2003-present):


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Researcher Biographical Page

Last name

Lee

First name

Joseph H.

Credentials

DrPH

Title

Assistant Professor

Location of your lab

Office:PH19-305

Location of your clinic

URL of your lab home page:

http://www.mailmanschool.org/msphfacdir/profile.asp?dept=Epidemiology&uni=jhl2

Researcher picture and lab art:

JHL2@Columbia.edu

Research Theme and Projects in your lab:

Identification and characterization of genetic and environmental factors that influence Alzheimer Disease as well as other aging traits

If you see patients, in which clinic do you attend

N/A

Education and Training Programs to which you belong

Epidemiology -- Genetic epidemiology track
Genetics of complex disorders training program

Bullet List of Genetic Diseases on which you work:

Alzheimer disease
Cognition
Aging
Obesity

Six Selected Publications (2003-present):

Lee JH, Cheng R, Santana V, Williamson J, Lantigua R, Medrano M,  Arriaga A, Stern Y, Tycko B, Rogaeva E, Wakutani Y, Kawarai T, St George-Hyslop P, Mayeux R. Expanded genome-wide scan implicates a novel locus at 3q28 among Caribbean Hispanics with familial Alzheimer’s disease. Archives of Neurology. (in press)

Lee JH, Lee H-S, Rogaeva E, Cheng R, Santana V, Williamson J, Lantigua R, Medrano M, Tycko B, Stern Y, St. George-Hyslop P, Mayeux R. Genetic dissection of Alzheimer disease at chromosome 12p using memory traits. (under review)

Lee JH*, Mayeux R*, Mayo D, Mo J, Santana V, Williamson J, Flaquer A, Ciappa A, Rondon HZ, Estevez P, Lantigua R, Kawarai T, Toulina A, Medrano M, Torres M, Stern Y, Tycko B, Rogaeva E, St George-Hyslop P, Knowles JA. Fine mapping of 10q and 18q for familial Alzheimer disease among Caribbean Hispanics. Molecular Psychiatry 2004;9(11):1042-1051.

Lee JH. Genetic evidence for cognitive reserve: variations in memory and related cognitive functions. Journal of Clinical and Experimental Neuropsychology 2003;25(5):594-613.

Lee JH, Flaquer A, Stern Y, Tycko B, Mayeux R. Genetic influences on memory performance in familial Alzheimer’s disease. Neurology 2004;62: 414-421.

Terwilliger JD, Lee JH. Natural Experiments in Human Gene Mapping:  The intersection of Anthropological Genetics and Genetic Epidemiology. In: Anthropological genetics: Theory, methods and applications. Crawford MH. (Ed.), Cambridge: University of Cambridge Press, 2006, pp. 38-76.

* Equal contribution

 

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Researcher Biographical Page

Last name

Levy

First name

Brynn

Credentials

M.Sc.(Med)., Ph.D., FACMG

Title

Associate Professor of Clinical Pathology

Location of your lab
Location of your clinic
URL of your lab home page:

Clinical Lab: (CHC 409) ; Research Lab: P&S 16-417

http://156.111.235.11/pharm/cumc/profile.php?id=268

Researcher picture and lab art:

Brynn Levy

Research Theme and Projects in your lab:

My principal research interest is in “Reproductive Genetics”. The spectrum of interests covered under the topic of “Reproductive Genetics” is quite broad encompassing the study of mechanisms involved in normal sex differentiation, preimplantation genetic diagnosis, critical gene expression at implantation, factors that contribute to infertility, the etiology of miscarriages, elements that are critical for healthy pregnancies, the improvement of current prenatal diagnostic tests and the development of non-invasive prenatal screening tests.

Current Projects: [1] We are currently developing “cytogenetic“ microarrays for detection of total aneuploidy, sub-telomeric deletions and common and novel micro-deletions. [2]. Aneuploidy analysis of single cells using conventional and array comparative genomic hybridization as well as oligonucleotide microarrays. We have been working extensively with whole genome amplification techniques that provide sufficient DNA for downstream analyses.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Cytogenetics Fellowship – American Board of Medical Genetics Training program

Bullet List of Genetic Diseases on which you work:

Chromosomal Abnormalities
Microdeletions
Microduplications

Six Selected Publications (2003-present):

1. Gorgoulis, V.G., Vassiliou, L.V., Karakaidos, P., Zacharatos, P., Kotsinas, A., Liloglou, T., Venere, M., DiTullio Jr., R.A., Kastrinakis, N.G., Levy, B., Kletsas, D., Yoneta, A., Herlyn, M., Kittas, C. and Halazonetis, T.D. Activation of the DNA damage checkpoint is an early event in the natural history of human cancer. Nature 2005;434:907-913.

2. Menasha, J., Levy, B., Hirschhorn, K., Kardon, N.B. The Incidence and Spectrum of Chromosome Abnormalities in Spontaneous Abortions: New insights from a 12 year study. Genet Med 2005;7(4):251-263.

3. Shanske, A.L., Edelmann, L., Kardon, N.B., Gosset, P., Levy, B. Detection of an interstitial deletion of 2q by comparative genomic hybridization in a child with multiple congenital abnormalities and an apparent balanced translocation. Am J Med Genet 2004;131A:29-35.

4. Miller KA, Elkind-Hirsch K, Levy B, Graubert MD, Ross SJ, Scott Jr R.T. Pregnancy following cryopreservation of donar oocytes and preimplantation genetic diagnosis (PGD) of the embryos in a patient with ovarian failure: a case report. Fertil Steril 2004;82:211-214.

5. Wells, D. and Levy, B. Cytogenetics in reproductive medicine: the contribution of comparative genomic hybridization (CGH). Bioessays. 2003 Mar;25(3):289-300.

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Researcher Biographical Page

Last name

Marder

First name

Karen

Credentials

MD MPH

Title

Sally Kerlin Professor Neurology

Location of your lab

(in the Sergievsky Center, Taub Institute and Psychiatry) at the CUMC

Location of your clinic

Neuro Inst 1st Floor (Aging and Dementia), PI 1st Floor (Huntington’s)

URL of your lab home page:

www.hdny.org

Researcher picture and lab art:

Marder, Karen

Research Theme and Projects in your lab:

My research has focused on genetic and environmental risk factors for PD and PD with dementia and Huntington’s disease. In the population-based sample of PD patients in the multi-ethnic community of Washington Heights, we found that relatives of PD patients were over twice as likely as relatives of controls to have PD, suggesting either an increased genetic risk in a small number of families or a smaller risk spread over many families. Relatives of demented patients were three times as likely to have AD as relatives of controls, suggesting a shared susceptibility to AD and PD. These observations lead to a grant funded in 1998 entitled The Genetic Epidemiology of PD (NS36630). In this study we confirmed the increased risk of PD in relatives of PD cases compared to relatives of controls. Relatives of PD cases whose age at onset was <50 and those with an age at onset >50 had a similar increase risk of PD (2-3 fold), suggesting that while the genetic risk factors might differ among PD cases with early and late onset cases, familial risks are similar. In collaboration with Dr. Lorraine Clarke, we have examined mutations in several genes associated with PD including parkin, LRRK2, DJ1 and GBA. Our goal is to establish the penetrance and phenotypic profile of both symptomatic and presymptomatic individuals who carry these mutations and determine whether cognitive and psychiatric manifestations occur prior to the defining motor features.

200 families with Huntington’s disease (HD) are followed at Columbia. We have conducted in collaboration with the Huntington Study Group, a number of NIH or FDA funded clinical trials including coenzyme Q10 and remacemide, riluzole, creatine, phenylbutyrate, and minocyline. Two observational studies have focused on the at-risk group (gene- positive and gene-negative (PHAROS), and those who are gene positive but presymptomatic (PREDICT-HD). The goals of these studies are to refine the criteria for onset of HD in order to more precisely power clinical trials in presymptomatic individuals. We are also using motor performance tasks to detect early changes in presymptomatic individuals not yet apparent on clinical exam. Lastly we have been studying caloric intake and energy expenditure in symptomatic and presymptomatic individuals.

If you see patients, in which clinic do you attend

Dr. Marder is the head of the Division of Aging and Dementia. She and her colleagues see patients with a variety of neurodegenerative disorders including Alzheimer’s disease, Dementia with Lewy Bodies, Frontotemporal dementia with or without ALS, corticobasal degeneration and vascular dementia.

Columbia-Presbyterian Medical Center
Lucy G. Moses Center for Memory and Behavioral Disorders

Neurological Institute
710 West 168th Street (212) 305-6939
Monday-Friday

Individuals with Huntington’s disease or at risk for Huntington’s disease can be seen at:

HDSA Center of Excellence at the New York State Psychiatric Institute
1051 Riverside Drive, Room 1501
(212) 305-9172
Friday only

Education and Training Programs to which you belong

Director of the United Council of Neurologic Subspecialties (UCNS) program in Behavioral Neurology and Neuropsychiatry

Faculty
Neuropsychology and Cognition in Aging
Research Training in Geriatric Psychiatary

Bullet List of Genetic Diseases on which you work:

Parkinson’s disease
Huntington’s disease
Alzheimer’s disease
Frontotemporal dementia+/- motor neuron disease

Six Selected Publications (2003-present):

Levy G, Schupf N, Tang MX, Cote L, Louis E, Mejia H, Stern Y, Marder K. Combined effect of age and severity on the risk of dementia in Parkinson’s disease. Ann Neurol 2002;51:722-729.

Marder K, Levy G, Louis ED, Mejia-Santana H, Cote L, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Ottman R. Familial Aggregation of Early and Late-Onset Parkinson’s Disease. Ann Neurol 2003;54:507-513

Levy G, Louis ED, Mejia-Santana H, Cote L, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Ottman R, Marder K. Lack of Familial Aggregation of Parkinson’s Disease and Alzheimer’s Disease. Arch Neurol 2004;61:1033-1039.

Gaba A, Zhang K, Marder K, Moskowitz C, Werner P, Boozer CN. Energy balance in early-stage Huntington’s disease. AJCN 2005;81;1335-1341

Clark L, Afridi S, Karlins E, Wang Y, Mejia-Santana H, Harris J, Louis E, Cote L, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. Case-control study of the Parkin gene in early-onset Parkinson’s Disease. Arch Neurol. 2006;63:548-552


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Researcher Biographical Page

Last name

Mayeux

First name

Richard

Credentials

M.D., M.Sc.

Title

Gertrude H. Sergievsky Professor

Location of your lab

PH-19, CUMC

Location of your clinic

Core Director of Human Genetics Resources Core (Black 16)

URL of your lab home page:

http://www.cumc.columbia.edu/dept/sergievsky
http://www.cumc.columbia.edu/dept/taub
http://human-genetics-resources-core.cumc.columbia.edu

Researcher picture and lab art:

Richard Mayeux

Research Theme and Projects in your lab:

My research is focused on the Epidemiology and Genetics of Alzheimer’s Disease (AD) in two unique cohorts. Since 1989 we have studied a random sample of African-American, Latino and white Medicare recipients living in the populations of in northern Manhattan. Over the past 19 years we have focused on the importance of both environmental and genetic factors and their interactions. We have studied the protective effects of alcohol, diet, education and postmenopausal hormone use as well as the deleterious effects of diabetes and hyperinsulinemia, head trauma, stroke, smoking and selected genetic variants in Alzheimer disease. These studies, which have defined patterns of disease, have identified important clues that may point to preventive treatments and must be understood in terms of molecular and cellular theories of Alzheimer disease.

Our family study based in the geographically isolated population in the Dominican Republic has identified over 500 multiplex families with Alzheimer’s disease, completed two genome wide scans and have investigated several genetic regions and candidate genes. We identified a novel founder mutation in Presenilin 1. Equally importantly, Mayeux and his colleagues found that APOE-ε4 and stroke combined to have a major impact on the risk of Alzheimer’s disease in families.

In addition, our research group at Columbia University is the coordinating site of the multicenter study of the National Institutes on Aging (NIA) Genetics Initiative for Late-Onset Alzheimer’s Disease (LOAD). This study is recruiting families with two or more affected siblings clinically or pathologically diagnosed with AD. The goal is to recruit 1,000 LOAD families. The first 362 families (including 2,105 family members) were part of a 6K SNP genome-wide scan at the NIH-supported, Center for Inherited Disease Research (CIDR) just completed.

If you see patients, in which clinic do you attend

Columbia-Presbyterian Medical Center
Lucy G. Moses Center for Memory and Behavioral Disorders
Neurological Institute

710 West 168th Street (212) 305-6939

Memory Disorders Center- New York State Psychiatric Institute, 1051 Riverside Drive, NY,NY 10032

Education and Training Programs to which you belong

Neuroepidemiology Training Program funded by NINDS has been in existence for 21 years and is currently the only program of its kind. Our mission is to prepare clinically oriented neuroscientists for research careers in the epidemiology of neurological disorders. The program has trained neurologists and neuroscientists who are now professors (5), associate professors (8), assistant professors (12), or career research scientists at the NIH and elsewhere (14). Many of the trainees have successfully competed for NIH funding and have established disease-specific neuroepidemiology research programs

The Neuropsychology and Cognition in Aging Training Program is designed to provide a solid research background in the cognition and neuropsychology of aging. The trainee is exposed to a broad range of interrelated research approaches, including classic neuropsychological evaluation, experimental cognitive techniques, genetic epidemiology, neuroepidemiology, pharmacological interventions, and cognitive neuroimaging.

Geriatric Psychiatry Training Grant (Roose, PI)
Genetic Epidemiology (Hodge, PI)

Bullet List of Genetic Diseases on which you work:

Neurological Disorders

• Alzheimer’s Disease
• Parkinson’s Disease
• Familial Dementias

Six Selected Publications (2003-present):

Lee JH, Mayeux R , Mayo D, Santana V, Williamson J, Flaquer A, Ciappa A, Rondon HZ, Estevez P, Lantigua R, Kawari T, Toulina A, Medrano M, Torres M, Stern Y, Tycko R, Rogaeva E, St George-Hyslop, Knowles JA. Fine mapping of 10q and 18q for familial Alzheimer disease in Caribbean Hispanics. Mol Psychiatry 2004; 9:1042-51.

Tycko B, Lee JH, Ciappa A, Saxena A, Li C-M, Lin Feng L, Arriaga A, Stern Y, Lantigua R, Yang L, Shachter NS Mayeux R. APOE and APOC1 promoter polymorphisms and Alzheimer’s disease in African-Americans and Caribbean Hispanics. Arch Neurol 2004; 61: 1434-9.

Devanand DP, Pelton GH, Zamora D, Liu X, Tabert MH, Goodkind M, Scarmeas N, Braun I, Stern Y, Mayeux R. Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment. Arch Neurol. 2005; 62 :975-80.

Rippon GA, Tang M-X, Lee JH, Lantigua R, Mayeux R. Familial Alzheimer Disease in Caribbean Hispanics: Interaction Between Stroke, Estrogen Replacement and APOE. Neurology 2006; 66:35-40.

Honig LS, Schupf N, Lee JH, Flores I, Tang M-X, Mayeux R. Short telomere repeat length is associated with mortality and dementia. Ann Neurol. 2006; 60: 181-7.

Shibata N, Kawarai T, Lee JH, Shibata E, Salehi-Rad S, Sato C, Morgan A, Mayeux RP, Rogaeva E, St George-Hyslop PH. Genetic study of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer’s disease. Neuroscience Letters 2006; 391:142-6.


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Researcher Biographical Page

Last name

Ottman

First name

Ruth

Credentials

Ph.D. (Genetics), University of California, Berkeley

Title

Professor of Epidemiology (in Neurology and the Sergievsky Center)

Location of your lab

Location of your clinic

PH19

URL of your lab home page:

http://www.cumc.columbia.edu/dept/epilepsy/
http://www.epilepsygenetics.org/

Researcher picture and lab art:

Ruth Ottman

Research Theme and Projects in your lab:

Ruth Ottman, Ph.D. is Professor of Epidemiology and Deputy Director for Research of the Sergievsky Center, Columbia University; and Research Scientist at the New York State Psychiatric Institute. She received an A.B. in zoology in 1975 and a Ph.D. in genetics in 1980 at the University of California, Berkeley, and completed a post-doc in cancer epidemiology at the same institution in 1981. She joined the faculty in epidemiology at Columbia University in 1981.

Dr. Ottman's primary area of expertise is genetic epidemiology. Her research focuses on the role of inherited factors in susceptibility to neurologic disorders, especially seizure disorders, migraine, essential tremor, and Parkinson's disease. She is also interested in methodologic issues in genetic epidemiology, including research designs for testing gene-environment interaction, methods for collection of valid family history data, and approaches to assessing familial aggregation.

Since 1985, she has devoted much of her effort to study of the genetic epidemiology of epilepsy. This work has included assessment of familial aggregation, shared vs. nonshared genetic influences on clinically-defined subgroups, consistency with various modes of inheritance, comorbidity of epilepsy and migraine, and reproductive rates in persons with epilepsy. In a series of studies, Dr. Ottman has explored possible explanations for the observation that risk of epilepsy is higher in offspring of affected women than in offspring of affected men. Her research group was the first to describe a form of temporal lobe epilepsy called “autosomal dominant partial epilepsy with auditory features” (ADPEAF).  They chromosomally localized the causative gene to chromosome 10q in a single large family, and later identified mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene in the original family and four others.

Dr. Ottman’s research group is currently conducting three studies of the genetic epidemiology of epilepsy. The first, a population-based study based in the Rochester (Minnesota) Epidemiology Project, is designed to assess clinical indicators of a genetic susceptibility to epilepsy. The second involves further assessment of the effect of mutations in LGI1 on ADPEAF and other forms of epilepsy, including estimation of penetrance, the range of phenotypic manifestations of mutations, and the proportion of ADPEAF families with mutations.  In the third study, they are attempting to localize and identify genes that raise risk for other forms of epilepsy, by analyzing a database of 81 families containing multiple affected individuals. 

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Genetics of Complex Diseases Training Program (Susan Hodge, D.Sc., principal investigator) (Predoctoral Training Director)
Robert Wood Johnson Health and Society Scholars Program (Biological Sciences Core Leader)

Bullet List of Genetic Diseases on which you work:

Epilepsy
Autosomal dominant partial epilepsy with auditory features (OMIM #600512)
Essential Tremor
Parkinson’s Disease

Six Selected Publications (2003-present):

Winawer MR, Rabinowitz D, Pedley TA, Hauser WA, Ottman R.  Genetic influences on myoclonic and absence seizures.  Neurology 2003;61:1576-1581.

Ottman R, Winawer MR, Kalachikov S, Barker-Cummings C, Gilliam CT, Pedley TA, Hauser WA.  LGI1 Mutations in autosomal dominant partial epilepsy with auditory features.  Neurology 2004;62:1120-1126.

Ottman R, Berenson K, Barker-Cummings C.  Recruitment of families for genetic studies of epilepsy.  Epilepsia 2005;46:290-297.

Winawer MR, Marini C, Grinton BE, Rabinowitz D, Berkovic SF, Scheffer IE, Ottman R.  Familial clustering of seizure types within the idiopathic generalized epilepsies.  Neurology 2005;65:523-528.

Choi H, Winawer MR, Kalachikov S, Pedley TA, Hauser WA, Ottman R.  Classification of partial seizure symptoms in genetic studies of the epilepsies. Neurology 2006;66:1648-1653.

Ottman R.  Analysis of genetically complex epilepsies.  Epilepsia 2005;46 (Suppl 10):7-14.

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Researcher Biographical Page

Last name

Pirzadeh

First name

Sara

Credentials

M.S.

Title

Genetic Counselor, Division of Clinical Genetics

Location of your lab

Location of your clinic

URL of your lab home page:

Researcher picture and lab art:

Research Theme and Projects in your lab:

If you see patients, in which clinic do you attend

Division of Clinical Genetics, BHN-601A
212-305-5802

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Six Selected Publications (2003-present):

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Researcher Biographical Page

Last name

Russo

First name

James J. (Jim)

Credentials

B.S. 1974 (St. John’s University, Biology); M.S. 1977 and Ph.D. 1981 (New York University School of Medicine, Cell Biology)

Title

Research Scientist, Associate Head of DNA Sequencing and Chemical Biology Laboratory, Columbia Genome Center

Location of your lab

Room 406, Russ Berrie Pavilion, 1150 St. Nicholas Avenue, New York, NY  10032

Location of your clinic

N/A

URL of your lab home page:

http://genome4.cpmc.columbia.edu/researcher/russo.html

Researcher picture and lab art:

Russo, James J. (Jim)

Research Theme and Projects in your lab:

The overriding theme in our group is the development and use of DNA sequencing and allied technologies to address biological questions.  This includes many diverse areas, based on internal and collaborative interests.

We have used directed and high throughput sequencing for a number of purposes:

  • To determine complete genomes (e.g., the 140 kb genome of HHV8, the herpesvirus associated with Kaposi sarcoma in AIDS patients and others; the 3.4 Mb genome of Legionella pneumophila, the bacterium responsible for Legionnaires’ disease and Pontiac fever).
  • To compare genomes in multiple species, strains, or individuals
  • To aid in linkage studies in informative pedigrees displaying inheritance of genetic diseases and cancers (this has included sequencing of RDA, EST, full length cDNA, exon trapping, and RACE clone libraries, as well as resequencing of disease loci for mutation detection and analysis)
  • To carry out association studies for complex diseases (focusing on SNPs, indels, microsatellites, RFLPs, and haplotypes)
  • To perform expression studies (EST, SAGE and microRNA library sequencing) and genotype:phenotype correlation (via characterization and use of transposon libraries for gene knockout in bacterial strains)

Along with Drs. Jingyue Ju, Eric Kandel, and Nicholas Turro at Columbia University and Leonid Morozov at the University of Florida, we are developing and testing methods aimed at understanding the transcriptome of Aplysia californica, an ideal and well-characterized model organism for addressing questions related to learning behaviors and memory consolidation.  These include methods for tracking mRNAs from their site of synthesis to their site of translation in neurons via both live imaging technologies (development of new classes of molecular beacons and binary molecular probes) and sequencing of cDNAs derived from transcripts collected from different stages of the transit process using newly developed massively parallel sequencing approaches as well as expression microarrays.

With Thomas Tuschl’s group at Rockefeller University, our laboratory has participated in generating and publishing numerous microRNA expression profiles in human and mouse tissues, including tumors and virally infected cells, as well as in zebrafish during their development, and most recently in portions of the Aplysia neural circuitry.

Members of our laboratory also have extensive experience with physical mapping technologies, having been part of the human chromosome 13 mapping group at Columbia spearheaded by Drs. Argiris Efstratiadis and Isidore Edelman during the early phases of the Human Genome Initiative, and in the creation and use of bioinformatics tools.  Thus we are uniquely positioned at the interface of discovery science (generation of massive data sets for subsequent analysis) and more traditional hypothesis driven research that still requires large scale approaches and equipment, and are primed for abetting investigations in systems biology.

If you see patients, in which clinic do you attend

N/A

Education and Training Programs to which you belong

In partnership with Dr. Jingyue Ju, our laboratory hosts many high school, undergraduate, graduate and postdoctoral trainees each year.  I am the co-director of a spring semester Undergraduate and Graduate course in Genetics and Genomics in the Department of Biological Sciences (W3031/W4031), and have sponsored many students in the Biotechnology master’s program (research credits and/or thesis) affiliated with that department.  I lecture in various courses at the medical campus and Dept. of Chemical Engineering on Columbia’s main campus.  In addition, I am the Director of the Minority Action Plan (MAP) of Dr. Ju’s Center of Excellence in Genomic Science. 

Bullet List of Genetic Diseases on which you work:

Most studies involving genetic diseases have been collaborative projects with faculty at Columbia.  As alluded to above, we have participated in linkage and association studies for simple and complex genetic diseases, oncogene searches around translocation breakpoints, and tumor suppressor gene hunts based on prior deletion or LOH analysis.

Short list of current disease-based projects and primary collaborators:

  • Depression/suicide – J. John Mann, Fatima (Victoria) Haghighi – gene association study
  • Alzheimer’s disease – Richard Mayeux, Joseph Lee, Benjamin Tycko – gene association study
  • Pathogenesis of aneurysms and other circulatory lesions – John Connolly, Eric J. Heyer – SNP association studies
  • ALS (Lou Gehrig’s disease) – Andreas Kottman – gene association study
  • Hepatoma, chronic lymphocytic leukemia (CLL) – Tom Tuschl and various European collaborators – microarray associations

Partial list of previous disease interests and major collaborators:

  • B-cell tumors (CLL, lymphomas, myelomas) – Riccardo Dalla-Favera – regional sequencing and clone library sequencing for gene searches
  • Breast cancer – Ramon Parsons – RDA library sequencing
  • Congenital generalized hypertrichosis (atavistic “Werwolf” syndrome) – Angela Christiano – sequencing of genes for mutations in linkage region
  • Long QT syndrome – Andrew R. Marks,  Robert S. Kass – gene mutation analysis

Asthma, epilepsy, Wilson’s disease, ataxia telangiectasia, ICF syndrome, retinoblastoma, other breast cancer projects, bipolar disorder, schizophrenia – numerous investigators at Columbia and elsewhere

Six Selected Publications (2003-present):

Martí, A.A., Li, X., Jockusch, S., Li, Z., Raveendra, B., Kalachikov, S., Russo, J.J., Morozova, I., Puthanveettil, S.V., Ju, J., Turro, N.J. (2006) Pyrene binary probes for unambiguous detection of mRNA using time-resolved fluorescence spectroscopy.  Nucleic Acids Res. 34:3161-3168.

Aravin, A., Gaidatzis, D., Pfeffer, S., Lagos-Quintana, M., Landgraf, P., Iovino, N., Morris, P., Brownstein, M.J., Kuramochi-Miyagawa, S., Nakano, T., Chien, M., Russo, J.J., Ju, J., Sheridan, R., Sander, C., Zavolan, M., Tuschl, T. (2006) A novel class of small RNAs bind to MILI protein in mouse testes.  Nature 442:203-207.

Chien, M., Morozova, I., Shi, S., Sheng, H., Chen, J., Gomez, S.M., Asamani, G., Hill, K., Nuara, J., Feder, M., Rineer, J., Greenberg, J.J., Steshenko, V., Park, S.H., Zhao, B., Teplitskaya, E., Edwards, J.R., Pampou, S., Georghiou, A., Chou, I.-C., Iannuccilli, W., Ulz, M.E., Kim, D.H., Geringer-Sameth, A., Goldsberry, C., Morozov, P., Fischer, S.G., Segal, G., Qu, X., Rzhetsky, A., Zhang, P., Cayanis, E., De Jong, P.J., Ju, J., Kalachikov, S., Shuman, H.A., Russo, J.J. (2004) The genomic sequence of the accidental pathogen Legionella pneumophila. Science 305:1966-1968.

Pfeffer, S., Zavolan, M., Grasser, F.A., Chien, M., Russo, J.J., Ju, J., John, B., Enright, A.J., Marks, D., Sander, C. and Tuschl, T. (2004) Identification of virus-encoded microRNAs. Science 304:734-736.

Morozova, I., Qu, X., Shi, S., Asamani, G., Greenberg, J., Shuman, H.A. and Russo, J.J.  (2004) Comparative sequence analysis of the icm/dot genes in Legionella.  Plasmid 51:127-147

Kim, S., Shi, S., Bonome, T., Ulz, M.E., Edwards, J.R., Fodstad, H., Russo, J.J. and Ju, J. (2003) Multiplex genotyping of the human b2-adrenergic receptor gene using solid-phase capturable dideoxynucleotides and mass spectrometry.  Anal Biochem 316:251-258.


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Researcher Biographical Page

Last name

Santella

First name

Regina

Credentials

PhD

Title

Professor of Environmental Health Sciences

Location of your lab

P&S19-418

Location of your clinic

URL of your lab home page:

http://www.columbia.edu/~rps1/index.html

Researcher picture and lab art:

Santella, Regina

Research Theme and Projects in your lab:

Dr. Santella’s research involves the development of laboratory methods for the detection of human exposure to environmental and occupational carcinogens and their use in molecular epidemiology studies to identify causative factors, susceptible populations, and preventive interventions. One aspect of her work has concentrated on the measurement of carcinogens bound to DNA with highly specific and sensitive immunoassays using monoclonal and polyclonal antibodies her laboratory has developed. These assays have measured exposure to polycyclic aromatic hydrocarbons, ubiquitous environmental pollutants, aflatoxin B1, a dietary mold contaminant, 4-aminobiphenyl, a carcinogen of cigarette smoke and oxidative stress as measured by 8-oxodeoxyguanosine.  To look at gene-environment interactions, high throughput genotyping methods are used to determine polymorphisms in a number of pathways including DNA repair, carcinogen and hormone metabolism,  oxidative stress and others that may influence cancer risk. Assays of DNA repair phenotype are also being developed for several different DNA repair pathways. These methods are currently being used for studies in liver, lung, breast and prostate cancer.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

1R25 (Neugut) NIH/NCI                                                                                 $396,412  (No Salary Support)
Training Program in Cancer-Related Population Sciences
T32 (Neugut) NIH/NCI
Training Program in Molecular Epidemiology
T32 (Brandt-Rauf) NIH/NIEHS
Training Program in Environmental Health Sciences

Bullet List of Genetic Diseases on which you work:

Cancer

Six Selected Publications (2003-present):

Paracchini, V., Chang, S.S., Santella, R.M., Garte,S., Pedotti, P., Taioli, E. GSTM1 deletion modifies the levels of polycyclic aromtic hydrocarbon-DNA adducts in human sperm Mutation Res. 586, 97-101, 2005.

Shen, J.Terry, M.B.,  Gammon, M.D., Zhang, F.F., Teitelbaum, S.L., Eng, S.M., Sagiv, S.K., Gaudet, M.M.,  Neugut, A. I., and Santella, R.M.  MGMT genotype, haplotype and susceptibility to breast cancer –– evidence from a population-based case-control study. Carcinogeneis 12, 2131-2137, 2005

Shen, J.Terry, M.B.,  Gammon, M.D., Gaudet, M.M., Teitelbaum, S.L., Eng, S.M., Sagiv, S.K., Neugut, A. I., and Santella, R.M. IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH-DNA adducts to breast cancer risk. Breast Cancer Research and Treatment 99. 1-7, 2006.

Rossner, P., Terry, M.B.,  Gammon, M.D., Zhang, F.F., Teitelbaum, S.L., Eng, S.M., Sagiv, S.K., Gaudet, M.M.,  Neugut, A. I., and Santella, R.M. OGG1 polymorphism and breast cancer risk. Cancer Epi. Biomarkers & Prevention 15, 811-5, 2006.

Terry, M.B., Gammon, M.D., Zhang, F.F., Knight, J.A., Wang, Q., Britton, J.A., Teitelbaum, S.L., Neugut, A.I. and Santella, R.M.  ADH3 genotype, alcohol intake, and breast cancer risk. Carcinogenesis 27, 840-847, 2006.

Shen, J., Desai, M.,  Agrawal, M., Kennedy, D., Senie, R.S., Santella, R.M. and Terry, M.B. Polymorphisms in nucleotide excision repair genes and DNA repair capacity in sisters discordant for breast cancer Cancer Epi., Biomarkers & Prevention in press

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Researcher Biographical Page

Last name

Schon

First name

Eric

Credentials

PhD

Title

Lewis P. Rowland Professor of Neurology
Professor of Genetics and Development (in Neurology)

Location of your lab

P&S 4-431

Location of your clinic

URL of your lab home page:

http://cpmcnet.columbia.edu/dept/genetics/faculties/Schon.html

Researcher picture and lab art:

Eric Schon

Research Theme and Projects in your lab:

Our laboratory studies the molecular genetics of neurological and neuromuscular diseases, with particular focus on mitochondrial disorders. Our research has two principal goals: (1) to use the tools of molecular biology in order to gain insight into the etiology, pathogenesis, and treatment of these devastating diseases, and (2) to build on this knowledge in order to ask more fundamental biological questions relating to nuclear-mitochondrial communication, mitochondrial biogenesis, mtDNA plasticity and recombination, and structure-function relationships of respiratory chain enzymes.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Genetics and Development
Integrated Program
MD-PhD Program
Motor Neuron Center
Vision Sciences Grant

Bullet List of Genetic Diseases on which you work:

Mitochondrial Dieases
(Kearns-Sayre syndrome; MERRF; MELAS; NARP/MILS)

Six Selected Publications (2003-present):

193. DiMauro S, Schon EA (2003). Mitochondrial respiratory chain diseases. N. Engl. J. Med. 348, 2656-2668.

195. Gajewski CD, Yang Y, Schon EA, Manfredi G (2003). New insights into the bioenergetics of mitochondrial disorders using intracellular ATP reporters. Mol. Biol. Cell 3628-3635.

196. Schon EA, DiMauro S (2003). Medicinal and genetic approaches to the treatment of mitochondrial disease. Curr. Med. Chem. 10, 2523-2533.

204. Santra S, Gilkerson RW, Davidson M, Schon EA (2004). Ketogenic treatment reduces deleted mitochondrial DNAs in cultured human cells. Ann. Neurol. 56, 662-669.

208. Naini A, Kaufmann P, Engelstad K, Shanske S, De Vivo D, Schon EA (2004). Hypocitrullinemia in patients with MELAS: an insight into the "MELAS paradox." J. Neurol. Sci., 229-230, 187-193.

209. Williams JC, Sue C, Banting GS, Yang H, Glerum DM, Hendrickson WA, Schon EA (2005) Crystal structure of human SCO1: implications for redox signaling by a mitochondrial cytochrome c oxidase "assembly" protein. J. Biol. Chem. 280, 15202-152011.

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Researcher Biographical Page

Last name

Schupf

First name

Nicole

Credentials

Ph.D., M.P.H., Dr. P.H

Title

Location of your lab

PH19: 304

Location of your clinic

URL of your lab home page:

Researcher picture and lab art:

Nicole Schupf

Research Theme and Projects in your lab:

Our group conducts studies of aging and Alzheimer’s disease in adults with Down syndrome, in collaboration with colleagues at the NYS Institute for Basic Research. A major focus of current work is the investigation of genetic and host factors that increase ß -amyloid load or accelerate the accumulation of fibrillized amyloid plaques. We are examining the relation of these factors to age at onset and risk for Alzheimer’s disease.

Recent work includes investigation of the relation of plasma amyloid ß peptides to onset of dementia in adults with Down syndrome. We have shown that Aß1-42 and Aß1-40 levels are significantly higher in adults with DS than in controls from the general population and that Aß1-42 levels are selectively increased in adults with DS with who develop AD compared with those who remain free of dementia over the study period. These findings support the hypothesis that individual differences in Aß processing, distinct from overexpression of APP, may act as an initial step in the pathogenesis of AD.

We have conducted studies of the relationship between estrogen deficiency, indicated by age at onset of menopause, apolipoprotein E genotype and age at onset of Alzheimer’s disease in women with Down syndrome. We have shown that onset of dementia is associated with age at menopause in women with Down syndrome, and that this association is independent of APOE genotype. Hormonal studies have found that free or bioavailable estrogen levels, rather than total estrogen levels, are associated with dementia. These findings support a neuroprotective role for estrogen. Our current work investigates the influence of polymorphisms in genes involved in estrogen biosynthesis and estrogen receptor function to rate of cognitive decline, to level and rate of decline of plasma amyloid ß peptides and to risk of Alzheimer’s disease (AD) in women with Down syndrome (DS).

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Mailman School of Public Health, Department of Epidemiology

Bullet List of Genetic Diseases on which you work:

1. Down syndrome
2. Alzheimer’s disease

Six Selected Publications (2003-present):

N. Schupf, D. Pang, BN Patel, W. Silverman, R. Schubert, F. Lai, JK Kline, Y Stern, M Ferin, B. Tycko, R. Mayeux (2003) Onset of dementia is associated with age at menopause in women with Down syndrome. Annals of Neurology 54:433-438

B.N. Patel, D. Pang, Y. Stern, W. Silverman, J.K Kline, R. Mayeux, N. Schupf. (2004) Obesity enhances verbal memory in postmenopausal women with Down syndrome. Neurobiology of Aging, 25: 159-166.W.

W. Silverman, N. Schupf, W. Zigman, D. Devenny, C. Miezejeski, R. Schubert, R. Ryan (2004). Dementia in adults with mental retardation: Assessment at a single point of time. American Journal of Mental Retardation 109 (2):111-125.

N. Schupf, R. Costa, M-X Tang, H. Andrews, B. Tycko, R. Mayeux (2004). Preservation of cognitive and functional ability as markers of family longevity. Neurobiology of Aging 25 (9):1231-1240.

W.B. Zigman, E.C. Jenkins, B. Tycko, N. Schupf, W. Silverman (2005). Mortality is associated with Apolipoprotein E in nondemented adults with Down syndrome. Neuroscience Letters 390 (2) 93-97.

Schupf, N. Winsten, S.,Patel, B.,Pang, D.,Ferin, M.,Zigman, W. B.,Silverman, W.,Mayeux, R (2006). Bioavailable estradiol and age at onset of Alzheimer’s disease in postmenopausal women with Down syndrome, Neuroscience Letters, 406(3):298-302.

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Researcher Biographical Page

Last name

Spitalnik

First name

Steven

Credentials

MD

Title

Vice Chairman and Professor of Pathology (Columbia),
Medical Director of Clinical Laboratory Services (NYPH)
Vice Chair of Pathology

Location of your lab

P&S 15-408

Location of your clinic

URL of your lab home page:

http://156.111.235.11/pharm/cumc/profile.php?id=37

Researcher picture and lab art:

Steven Spitalnik

Research Theme and Projects in your lab:

As a glycobiologist, I am interested in the biochemistry, cell biology, and immunology of glycoproteins and glycolipids.

Biology of the human glycophorin blood group antigens:
Glycophorin A is the most abundant glycoprotein on human RBC and carries oligosaccharide, peptide, and glycopeptide blood group antigens. It is important in transfusion medicine because antibodies recognizing these antigens cause autoimmune hemolytic anemia, hemolytic transfusion reactions, and hemolytic disease of the newborn. We are currently using glycophorin A as a model “mini-mucin” to study the rules governing site-specific O-glycosylation. In addition, we are using Fab phage display methods and x-ray crystallography to study the interactions of blood group M- and N-specific monoclonal antibodies with their corresponding glycopeptide antigens. Finally, we are using human glycophorin A transgenic mice to develop animal models of hemolytic transfusion reactions and hemolytic disease of the newborn.

Glycobiology of Toxoplasma gondii:
T. gondii is an obligate intracellular single-celled protozoan parasite and human pathogen that causes chronic, life threatening infections in immunocompromised patients. Given its small haploid genome, the completion of the T. gondii genome project, its ease of culture in vitro and in vivo, the availability of powerful methods for creating knockout and transgenic organisms, and the presence of a well-defined and well-characterized secretory pathway, it is a useful model for pathobiological, cell biological, and genetic studies. We are using T. gondii as a model to study the role of mucin-type O-glycosylation in the pathobiology of toxoplasmosis. In addition, given that T. gondii has a simple developmental program with three distinct life forms, it offers an opportunity for studying mucin-type O-glycosylation in development. We completed the cloning, expression, and enzymatic characterization of the entire family of five polypeptide:GalNAc transferases encoded by T. gondii. These enzymes initiate protein O-glycosylation. We plan to knock out each member of this T. gondii gene family and examine the biological and biochemical phenotype of the knockout parasites.

If you see patients, in which clinic do you attend

I am the Medical Director of the Clinical Laboratory Services at NYPH-CUMC. As such, I am responsible for ensuring that relevant genetics tests are either performed at NYPH-CUMC or are “sent out” to appropriate, specialized, referral laboratories.

Education and Training Programs to which you belong

I direct the residency training program in clinical pathology (i.e. laboratory medicine). I am also a member of the graduate program in pathobiology at Columbia University.

Bullet List of Genetic Diseases on which you work:

Six Selected Publications (2003-present):

1. Song, SC, Czerwinski M, Wojczyk BS, Spitalnik SL. Alteration of amino acid residues at the L chain N-terminus and in CDR3 increases affinity of a recombinant Fab for a human glycopeptide blood group antigen. Transfusion 44:173-186, 2004.

2. Stwora-Wojczyk MM, Kissinger JC, Spitalnik SL, Wojczyk BS. O-glycosylation in Toxoplasma gondii: Identification and analysis of a family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. Intl J Parasitol 34:309-322, 2004.

3. Song SC, Xie K, Czerwinski M, Spitalnik SL, Wedekind JE. Purification, crystallization, and X-ray diffraction analysis of a recombinant Fab that recognizes a human blood group antigen. Acta Crystallographica D60:788-791, 2004.

4. Stwora-Wojczyk MM, Dzierszinski F, Spitalnik SL, Wojczyk BS. Molecular cloning, purification, and expression of UDP-N-acetyl-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase T3 from Toxoplasma gondii. Arch Biochem Biophys 426:231-240, 2004.

5. Wojczyk BS, Takahashi N, Tsukamoto Y, Levy MT, Andrews DW, Abrams WR, Wunner WH, Spitalnik SL. N-Glycosylation at one rabies virus glycoprotein sequon influences N-glycan processing at a distant sequon on the same molecule. Glycobiology 15:655-666, 2005.

6. Xie K, Song SC, Spitalnik SL, Wedekind JE. Crystallographic analysis of the NNA7 Fab and proposal for the mode of human blood-group recognition. Acta Crystallographica D61:1386-1394, 2005.

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Researcher Biographical Page

Last name

Terry

First name

Mary Beth

Credentials

PhD in Epidemiology

Title

Associate Professor

Location of your lab

Department of Epidemiology
Mailman School of Public Health
722 West 168th, Room 724

Location of your clinic

 

URL of your lab home page:

 

Researcher picture and lab art:

Research Theme and Projects in your lab:

Mary Beth Terry, PhD, is an Associate Professor of Epidemiology at Columbia University who has been involved in case-control studies of breast and colorectal cancer for over ten years. She currently leads several large epidemiologic studies focusing on the role of pre and postnatal factors on breast cancer risk. She also focuses on molecular epidemiology and gene environment interactions. She is a National Cancer Institute recipient of a 5-year R01 grant to study the relationship between early life factors and breast cancer and has related research on the role of epigenetics and breast cancer risk. Dr. Terry is also the PI of the New York Metropolitan Breast Cancer Registry which is a family registry of high risk women with and without breast cancer. Dr. Terry recently completed an NCI K07 Career Development Award and an American Cancer Society Clinical Training Award.

If you see patients, in which clinic do you attend

 

Education and Training Programs to which you belong

1R25 (Neugut) NIH/NCI $396,412 (No Salary Support)
Training Program in Cancer-Related Population Sciences
T32 (Neugut) NIH/NCI
Training Program in Molecular Epidemiology

Bullet List of Genetic Diseases on which you work:

Cancer

Six Selected Publications (2003-present):

 

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Researcher Biographical Page

Last name

Tsang

First name

Stephen

Credentials

MD, P&S 98’ and PhD. Columbia 96’
Jules Stein Eye Institute/UCLA ’03
Diplomate of the American Board of Ophthalmology

Title

Assistant Professor in Ophthalmology
Assistant Professor in Pathology

Location of your lab

Bernard & Shirlee Brown Glaucoma Laboratory
160 Fort Washington Avenue, Room 513

Location of your clinic

Louis V. Gerstner, Jr Retina Center

Edward S. Harkness Eye Institute

635 West 165th Street, NY 10032

URL of your lab home page:

www.cumc.columbia.edu/dept/eye/doctors/coc_tsang.html

Researcher picture and lab art:

Tsangpic1 Tsangpic2
Photo by Charlie Martin at Jules Stein Eye Inst.

Research Theme and Projects in your lab:

Stephen Tsang, M.D., Ph.D.’s research efforts are to find new treatments for photoreceptor degeneration in retinitis pigmentosa (RP), age-related macular degeneration (AMD) and related retinal dystrophies, the most common forms of degenerative disease in the central nervous system and have profound impact on quality of life. Over 9 million Americans are affected with photoreceptor degenerations, far exceeding the number with Alzheimer disease. Inherited forms of photoreceptor degeneration affect about one in 2000 people. Presently there is no cure.

RP is the most common cause of inherited blindness, named for the increased pigmentation that appears in the areas of retinal cell death during late manifestation of the disease. Initial symptoms include night blindness, due to the death of rod photoreceptor cells – the light-sensing neurons at the peripheral retina – resulting in “tunnel vision.” In later stages, RP destroys cone photoreceptor cells in the macula, responsible for fine central vision. One in ten Americans is a carrier for a defect in one of the 180 genes associated with RP. Our research has illuminated the mechanisms by which the phosphodiesterase (PDE6) signaling network regulates rod and cone survival. Defects in the PDE6 gene account for approximately 75,000 yearly cases of RP worldwide.

In related research initiatives, we study and manipulate photoreceptor degeneration gene expression in mice, which closely parallels similar conditions in humans. Their goal is to control the expression of this faulty PDE6 gene by using inducible gene targeting that allows the activity of a gene in a specific tissue to be disrupted at any time during the life of a mouse. By following the effects of the genetic abnormality after the photoreceptors have fully developed, they hope to gain an understanding of the early events controlling photoreceptor signaling and degeneration in mice, which could lead to new drug targets for the prevention or delay of human retinal degenerations.

Gaining temporal and spatial control of gene expression is essential for the elucidation of gene function in the whole organism. The reagents that we develop can be built into gene therapy vector to provide temporal and spatial control of gene expression of any therapeutic gene. An inducible gene targeting system can be used to address several previously unapproachable problems in sensory biology as well as gene therapy.

Furthermore, we believe that cell transplantation in the human retina has the potential to restore lost vision and provide treatment for advanced stages of retinal degeneration featuring significant photoreceptor neuronal loss, noting that a major obstacle for this approach is the ability to produce sufficient patient specific photoreceptor cells for transplantation. Adult retinal stem cells, which reside in the ciliary body of the adult human eye, are one potential source of photoreceptors. Fish regenerate retinal neurons from a population of stem cells that are intrinsic in the ciliary body, which surrounds the lens of the eye and maintains proper pressure in the eyeball; these cells reside within the differentiated retina throughout the lifetime of the animal. The progeny of fish stem cells can divide and migratory progenitors are the antecedents of photoreceptor precursors. It is these intrinsic adult retinal stem cells that allow the fish to regenerate photoreceptor neurons spontaneously when existing neurons are killed. Stem cell transplantation therefore has the potential to restore lost vision and provide treatment for advanced stages of retinal degeneration even in cases of significant photoreceptor loss in humans.

Our research paves the way toward “retinoplasty,” reconstruction of interfaces between photoreceptors and their environment after the onset of retinal degeneration. Our approach involves the culture of human retinal stem cells from the ciliary body in eye-bank globes, and using those cultured cells to determine the combination of transcription factors involved in regulating their proliferation and differentiation into light-sensing photoreceptor neurons. These experiments will identify the effectors regulating human retinal stem cell differentiation and proliferation, as well as testing the ability of in vitro generated stem cells to repopulate the diseased retina. Future applications may include patient-specific stem cells obtained from fine-needle aspiration of their ciliary bodies in the operating room. Based on our findings, we foresee the ability to manipulate the patients’ own stem cells to cure their specific disease. This approach will solve the problem of limited supply of allograft rejection by using a patient’s own cells.

If you see patients, in which clinic do you attend

Center for Genetic Eye Diseases and Louis V. Gerstner Jr Retina Center

Edward S. Harkness Eye Institute, 635 West 165th Street.

Tel: 212-342-0943

Education and Training Programs to which you belong

Cell Biology & Pathobiology Ph.D. Program
Nutrient Master Thesis Program

Bullet List of Genetic Diseases on which you work:

Macular degenerations,
Macular dystrophies,
Stargardt disease,
Best disease,
Pattern Dystrophies,
North Carolina macular dystrophy,
Choroideremia,
Retinitis pigmentosa,
Leber congenital amaurosis,
Cone dystrophies,
Cone-rod dystrophies,
Congenital Stationary night blindness,
Bradyopsia,
X-Linked Retinoschisis,
Hereditary vitreoretinopathies,
Refractive errors,
Congenital nystagmus,
Optic atrophies,
Albinism,
Foveal hypoplasia
Connective tissue disorders,
and Inborn errors of metabolism.

Six Selected Publications (2003-present):

Tsang, S. H., and Gouras, P. (2004) Photoreceptors and photoreceptor dysfunctions. In Encyclopedia of Neuroscience. G. Adelman and B. Smith, eds. (Amsterdam: Elsevier Science). 1633–1644.

Tsang, S. H., Woodruff, M. L., Chen, C. K., Yamashita, C. Y., Cilluffo, M. C., Rao, A. L., Farber, D. B., and Fain, G. L. (2006) GAP-independent termination of photoreceptor light response by excess gamma subunit of the cGMP-phosphodiesterase. J Neurosci 26, 4472-4480.
http://www.jneurosci.org/cgi/content/full/26/17/4472

Tsang, S. H., Woodruff ML, Lin J, Mahajan V, Yamashita CK, Petersen R, Lin CS, Goff, SP, Rosenberg T, Larsen M, Farber DB and Nusinowitz S Transgenic Mice Carrying the H258N Mutation in the Gene Encoding the beta-subunit of Phosphodiesterase-6 (PDE6B) Provide a Model for Human Congenital Stationary Night Blindness. Hum Mutat. 2007 Mar;28(3):243-54.
http://www3.interscience.wiley.com/cgi-bin/abstract/113399423/ABSTRACT?CRETRY=1&SRETRY=0

Tsang, SH, Woodruff, M.L. Janisch K., Farber, DB and Fain, GL Removal of Phosphorylation Sites of Gamma Subunit of Phosphodiesterase6 Alters Rod Light Response, Journal of Physiology. 2007 Mar 1;579:303-12 http://jp.physoc.org/cgi/content/abstract/jphysiol.2006.121772v2

Tsui, I., Song, B., Lin, C.-S., and Tsang, S.H. (2007). A Practical Approach to Retinal Dystrophies. Retinal Physician 4, 18-26. http://www.retinalphysician.com/article.aspx?article=100310

Tsang, S.H., Vaclavik, V, Bird, AC, Robson, AG, Holder, GH. Novel Phenotypic and Genotypic Findings in X-Linked Retinoschisis (XLRS) Archives of Ophthalmology. Arch Ophthalmol. 2007 Feb;125(2):259-67.


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Researcher Biographical Page

Last name

Vundavalli

First name

Murty

Credentials

Ph.D.

Title

Associate Professor

Location of your lab
Location of your clinic
URL of your lab home page:

1130 St. Nicholas Ave; Room 605
409 Babies Central

Researcher picture and lab art:

vvm2@columbia.edu

Research Theme and Projects in your lab:

Our laboratory is interested in understanding the genetic and epigenetic basis of cancer with specific goals to identify and characterize novel tumor suppressor genes and oncogenes in male germ cell tumor (GCT) and cervical cancer.

GCT, a common malignancy in young males, is a complex tumor system where germ cells undergo transformation and exhibit embryonal and extra-embryonal like differentiation patterns. We identified a critical region of heterozygous deletion and epigenetic silencing of genes in a large region at 12q22 implicating the role of both genetic and epigenetic alterations in suppressing a chromosomal domain. Extensive physical and deletion maps, sequence annotation and transcript maps, genetic and epigenetic characterization of 12q22 region have been generated in a prelude to identify the mechanisms of tumor suppression. We are currently further exploring the genetic and epigenetic mechanisms of tumor suppression related to 12q22 deletions in GCT.

Carcinoma of uterine cervix is a common malignancy among women worldwide. Most cervical cancers are preceded by distinct preneoplastic epithelial changes, which progress to invasive cancer, thus providing opportunities to study genetic alterations at an early stage of transformation. In a genome-wide search for genetic and epigenetic alterations, we identified several sites of deletions, gene amplifications, and specific gene pathways in invasive cancer. We are currently characterizing the target amplified and deleted genes, and identifying their origin in the development of precancerous lesions to develop a genetic prognostic model for progression.

If you see patients, in which clinic do you attend

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

Testicular germ cell tumor (%273300),
cervical cancer (#603956)

Six Selected Publications (2003-present):

1. Narayan G, Pulido HA, Koul S, Liu X-Y, Harris CP, Yeh YA, Vargas H, Posso H, Terry MB, Gissmann L, Schneider A, Mansukhani M, Rao PH, Murty VV. Genetic Deletions Affecting Chromosome 2q34-q35 and 2q36.3-q37.1 Identify Sites of Putative Tumor Suppressor Genes Involved in Cervical Cancer Progression. Oncogene.22: 3489-3499, 2003.

2. Michel L, Diaz-Rodriguez E, Narayan G, Murty VV, Benezra R. Complete loss of the tumor suppressor MAD2 causes premature cyclin B degradation and mitotic failure in human somatic cells. Proc Natl Acad Sci, USA 101: 4459-4464, 2004.

3. Narayan G, Arias-Pulido H, Nandula SV, Basso K, Sugirtharaj DD, Vargas H, Mansukhani M, Villella J, Meyer L, Schneider A, Gissmann L, Dürst M, Pothuri B, Murty VV: Promoter Hypermethylation of FANCF: Disruption of Fanconi Anemia-BRCA Pathway in Cervical Cancer. Cancer Res 64: 2994-2997, 2004.

4. Koul S, McKiernan JM, Narayan G, Houldsworth J, Bacik J, Dobrzynski DL, Assaad AM, Mansukhani M, Reuter VE, Bosl GJ, Chaganti RS, Murty VV. Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors. Molecular Cancer 3:16, 2004.

5. Cattoretti G, Pasqualucci L, Ballon G, Tam W, Nandula SV, Shen Q, Mo T, Murty VV, Riccardo Dalla-Favera R. Deregulated BCL6 expression recapitulates the pathogenesis of human diffuse large B-cell lymphomas in mice. Cancer Cell 7: 445-455, 2005.

6. Pasche B, Knobloch TJ, Bian Y, Liu J, Phukan S, Rosman D, Kaklamani V, Baddi L, Siddiqui FS, Frankel W, Prior TW, Schuller DE, Agrawal A, Lang J, Dolan ME, Vokes EE, Lane WS, Huang CC, Caldes T, Di Cristofano A, Hampel H, Nilsson I, von Heijne G, Fodde R, Murty VV, de la Chapelle A, Weghorst CM. Somatic acquisition and signaling of TGFBR1*6A in cancer. JAMA 294: 1634-1646, 2005.

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Researcher Biographical Page

Last name

Warburton

First name

Dorothy

Credentials

Ph.D. ABMG certified in Clinical Cytogenetics and Ph.D. Medical Genetics

Title

Location of your lab

CHC-407

Location of your clinic

N/A

URL of your lab home page:

N/A

Researcher picture and lab art:

Research Theme and Projects in your lab:

The lab studies human chromosomal aberrations, using conventional cytogenetics, molecular cytogenetics, and epidemiological methods. Currently we are involved in two main projects:

a. Investigations of Maternal-Age Related Aneuploidy

Maternal age is the only factor consistently related to the incidence of aneuploidy at conception. The incidence of oocytes with an abnormal chromosome number increases from about 10% in women under 25 to approximately 50% in women over 40, and the reason for this increase is not known. Our research has focused on epidemiological approaches to this problem, but we have recently also begun to study human oocyte material directly, using discarded oocytes retrieved for in vitro fertilization.

(1) Epidemiological studies of the relationship of ovarian age to trisomy at conception

We have proposed the hypothesis that the increase in trisomy with maternal age is directly related to the age-related decline in the size of the oocyte pool.  Previous studies have compared age at menopause, hormonal levels and number of antral follicles between women with a trisomic miscarriage, women with a chromosomally normal miscarriage and women with a livebirth.

We are currently studying the rates of highly skewed X-inactivation in women ascertained through a trisomic spontaneous abortion and controls. Skewed X inactivation has been reported to be increased among women with repeated spontaneous abortion. We hypothesize that this may be due to X chromosome mutations or lesions below the level of cytogenetic resolution, which lead to both increased follicular atresia and skewed X chromosome inactivation.  Genomic microarrays will be used to investigate X chromosome copy number changes in women with highly skewed X inactivation and controls.  We are also planning to use samples collected from this and previous studies to investigate the relationship between trisomic conceptions, hormonal measures of ovarian aging and fra(X) repeat size.

(2) Laboratory studies of human oocytes

Direct analysis of human oocytes will be used to investigate the hypothesis that accumulation of mitochondrial mutations with age leads to meiotic errors.  Discarded MII oocytes from an in vitro fertilization clinic will be analyzed for mitochondrial mutations as well as meiotic errors using comparative genomic hybridization after genomic amplification. Studies are also planned to examine amounts and localization of cohesins, proteins that are essential for correct meiotic chromosomal segregation.

b. Genomic Microarray Analysis to detect Sub-microscopic copy number changes

Recent studies using high-resolution genomic microarrays have shown that copy number variation is common, with two normal individuals differing in about 12 places in the genome with size ranges of 100 kb to 2 Mb.  Such changes may also be associated with developmental pathology, with frequencies yet to be determined.  We will study 350 children with congenital heart defects, and their parents, to determine the contribution of these high-resolution copy number changes to the etiology of this most common human congenital malformation. Genomic microarray analysis will be carried out using ROMA (representational oligonucleotide microarray analysis), in collaboration with Dr. Michael Wigler’s lab at the Cold Spring Harbor Laboratory.

If you see patients, in which clinic do you attend

Division of Clinical Genetics, Department of Pediatrics
212-305-6731

Education and Training Programs to which you belong

Genetics and Development Training Grant
Genetics of Complex Disorders Training Grant
ABMG Training Program in Clinical Cytogenetics and Molecular Genetics
ABMG Residency Program in Pediatrics

Bullet List of Genetic Diseases on which you work:

Constitutional chromosomal aberrations
Congenital Heart Disease
Autism

Six Selected Publications (2003-present):

Kline J, Kinney A, Ereuss ML, Kelly A, Leven B, Ferin M, Warburton D.  (2004) Trisomic pregnancy and the oocyte pool.  Human Reprod. 19:1633-1643.

Munne, S. Sandalinas M, Magli C. Gianaroli L, Cohen J, Warburton D.  (2004)  Increased rate of aneuploid embryos in young women with previous aneuploid conceptions.  Prenat Diagn.  24:638-643.

Warburton D, Dallaire L, Thangavelu M, Ross L, Levin B, Kline J.  (2004) Trisomy recurrence: a reconsideration based on North American Data. Am J Hum Genet.  75-376-385.

Jobanputra V, Sebat J, Troge J, Chung, W, Anyane-Yeboa K, Wigler M, Warburton D.  (2005)  Application of ROMA (Representational Oligonucleotide Microarray Analysis) to patients with cytogenetic rearrangements.  Genet Med. 7:111-118.

Warburton, D. 2005. Biological aging and the etiology of aneuploidy.  Cytogenet Genome Res 111: 266-272.

Kline J, Kinney A, Levin B, Kelly A, Yu C-Y, Brown S, Warburton D. 2006.  X-chromosome inactivation and ovarian age during the reproductive years.  Fertil Steril 2006; 85:1488-1495.



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Researcher Biographical Page

Last name

Weissman

First name

Myrna

Credentials

PhD

Title

Professor of Epidemiology in Psychiatry
Chief, Division of Clinical and Genetic Epidemiology

Location of your lab

N/A

Location of your clinic

N/A

URL of your lab home page:

N/A

Researcher picture and lab art:

Research Theme and Projects in your lab:

To understand the genetic basis of mood and anxiety disorders using epidemiologic and genetic methods in collaboration with investigators in molecular and statistical genetics and more recently, in neuroimaging.  We specialize in the screening, recruitment, phenotyping and collection of DNA of large samples for genetic studies; in the design and analysis of these studies; in the training and monitoring of clinical teams, the selection of and development of clinical assessments suitable for genetic studies; and in the managing of large data sets including tracking and monitoring progress and preparing data for analysis; and finally in the conduct of mult-site collaborative studies.

Mathematical Genetics Unit – This unit is part of the Division of Clinical and Genetic Epidemiology Unit at the New York State Psychiatric Institute and is headed by Susan Hodge, D. Sc. And David Greenberg, Ph.D. and will be described separately in their biographical page.

Current NIH grants include:

Children at High and Low Risk for Depression – The overall aim of this study is to understand the long-term

temporal sequence and familial patterns of mood and other disorders from childhood to adulthood in offspring at high and low risk for depression.  The study now includes three generations.  The aims during this project period are to (1) acquire and analyze both anatomical and functional MRI in 214 subjects and to collect blood for DNA and RNA and (2) conduct data analyses integrating clinical, genetic, psychophysiological and neuroimaging studies.

Genetics of Recurrent Early Onset Major Depression – This is a six-site cooperative project to collect a large sample of subjects with early-onset MDD obtaining clinical data and genetic samples aiming to map genes giving a susceptibility to MDD.  This is a renewal of a collaborative study.

Genetic Studies of Depressive Disorders – This is a project aimed at understanding the etiology of panic disorder using a broad range of novel and advanced genetic and epidemiologic approaches.  One hundred and thirty multiplex families with over a 1,000 family members and 100 triads with panic disorder have been collected and cell lines have been prepared.

Molecular Genetic Studies of Fear and Anxiety – The aim of this project is to study the molecular and genetic basis of amygdala-regulated fear and anxiety in mice and humans.  Several fear conditioning paradigms will be studied in both mice and humans, along with selected anxiety related traits and disorders in humans.  Genes that alter fear-conditioning phenotypes in mice will be analyzed for trait-related DNA sequence variation in humans who score at the phenotypic extremes for the matched paradigm.  Genes shown to alter other anxiety measurements in mice will be analyzed for trait or disorder-related variation in humans with a variety of anxiety-related temperaments and disorders.  Five hundred and fifty patients with panic disorder or social anxiety disorder have been collected and cell lines are available.  One hundred normal controls have been collected by our group and over 2,000 from the NIMH repository are available.

Risk of Substance Use and Abuse: A Three Generation Study – The aim of this study is to(1) examine the longitudinal course of drug use and smoking, including risk factors that lead to drug use and smoking and the course of drug use and smoking from childhood to adulthood (2) examine the impact of parental drug use and smoking on functioning and psychopathology in offspring, as well as the impact of maternal drug use and smoking during pregnancy on child outcomes and (3) to search for differences in brain function and structure that may account for substance use and other psychopathologies.  Blood for DNA is being collected.

If you see patients, in which clinic do you attend

We recruit patients nationwide including local clinics.  We are following a sample of 3 generations in which generations 1 and 2 were identified over 20 years ago.

Education and Training Programs to which you belong

The Mathematical Genetics Unit of the Genetics of Complex Disorders Training Program at Columbia University (Susan Hodge, D.Sc., – PI) – see description under Dr. Hodge

Psychiatric Epidemiology Training Program (PET) of the Department of Epidemiology at the Mailman School of Public Health (Bruce Link, Ph.D. – PI)

Research Training in Child Psychiatry (David Shaffer, M.D. – PI)

Bullet List of Genetic Diseases on which you work:

Major Depression and related depression
Panic Disorder
Social Anxiety Disorder

Six Selected Publications (2003-present):

1. Hamilton SP, Fyer AJ, Durner M, Heiman GA, deLeon AB, Hodge SE, Knowles JA, Weissman MM. Further genetic evidence for a panic disorder syndrome mapping to chromosome 13q. Proc Nat Acad Sciences (PNAS) 100(5):2550-2555, 2003.

2. Hamilton SP, Slager SL, Baisre de Leon A, Heiman GA, Klein DF, Hodge SE, Weissman MM, Fyer AJ, Knowles JA. Evidence for genetic linkage between a polymorphism in the Adenosine 2A receptor (ADORA2A) and panic disorder. Neuropsychopharmacology 29:558-565, 2004.

3. Hamilton SP, Slager SL, Mayo D, Heiman GA, Klein DF, Hodge SE, Fyer AJ, Weissman MM, Knowles JA. Investigation of polymorphisms in the CREM gene in panic disorder. Am J Med Genet 126B: 111-115, 2004.

4. Weissman MM , Gross R , Fyer AJ, Heiman GA, Gameroff  MJ, Hodge SE, Kaufman D, Kaplan SA, Wickramaratne PJ. Interstitial cystitis and panic disorder: A potential genetic syndrome. Arch Gen Psychiatry 61:273-279, 2004.

5. Fyer AJ, Hamilton SP, Durner M, Heiman GA, de Leon AB, Klein DF, Hodge SE, Tavares N, Weissman MM, Knowles JA. A Third Pass Genome Scan in Panic Disorder Evidence for Multiple Susceptibility Loci. Biol Psychiatry 60: 388-402, 2006.

6. Bruder GE, Tenke CE, Warner V, Nomura Y, Grillon C, Hille J, Leite P, Weissman MM.Electroencephalographic measures of regional hemispheric activity in offspring at risk for depressive disorders. Biol Psychiatry 57:328-335, 2005.

7. Weissman MM, Wickramaratne PJ, Nomura Y, Warner V, Verdeli H, Pilowsky DJ, Grillon C, Bruder G. Families at high and low risk for depression: A three generation study. Arch Gen Psychiatry 62: 29-36, 2005.

8. Grillon C, Warner V, Hille J, Merikangas KR, Bruder GE, Tenke CE, Nomura Y, Leite P, Weissman MM. Families at High and Low Risk for Depression: A Three Generation Startle Study. Biol Psychiatry 57: 953-960, 2005.

Holmans P, Weissman MM, Zubenko GS, Scheftner WS, Crowe RR, Depaulo JR, Knowles JA, Zubenko WN, Murphy-Eberenz K, Marta DH, Boutelle S, McInnis MG, Adams P, Gladis M, Thomas J, Chellis J, Miller E, Potash JB, MacKinnon D, Levinson DF. Genetics of Recurrent Early-Onset Major Depression (GenRED): Final Genome Scan Report. Am J Psychiatry. In press, 2006.


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Researcher Biographical Page

Last name

Williamson Catania

First name

Jennifer

Credentials

MS, CGC

Title

Senior Research Staff Associate

Location of your lab

Taub Institute/Sergievsky Center

Location of your clinic

New York State Psychiatric Institute (Huntington Disease Center and Memory Disorders Center)

URL of your lab home page:

www.hdny.org
www.alzheimercenter.org

Researcher picture and lab art:

Research Theme and Projects in your lab:

Coordinate genetic studies of neurodegenerative diseases including:
NIA Late Onset Alzheimer’s Disease Genetic Study
Neurobiological Predictors of Huntington’s Disease – PREDICT HD

If you see patients, in which clinic do you attend

Genetic counselor for the Huntington’s Disease Center of Excellence and Lucy G. Moses Center for  Memory and Behavioral Disorders

Education and Training Programs to which you belong

Bullet List of Genetic Diseases on which you work:

  • Alzheimer’s disease
  • Frontotemporal dementia
  • familial dementias
  • Huntington’s disease

Six Selected Publications (2003-present):

J. Williamson, S. LaRusse.  Update on Genetics and Genetic Counseling Recommendations: Alzheimer’s Disease, Frontotemporal Dementia and Creutzfeldt-Jakob Disease.  Current Neurology and Neuroscience Reports.  (2004) Sep;4(5):351-7.

L.J.  Ciarleglio, R. L. Bennett, J. Williamson, J.B. Mandell JB, J.H. Marks.  (2003)  Genetic counseling throughout the life cycle. J Clin Invest. 112(9):1280-6.


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