Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER

 

Columbia University
Medical Center
Neurological Institute

710 West 168th Street, 3rd floor
(212) 305-1818


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About Us

Taub Faculty

Catherine L. Clelland, M.S., Ph.D.

Catherine L. Clelland, M.S., Ph.D.

Assistant Professor of Clinical Pathology

Email: cc2786@columbia.edu

Dr. Clelland (nee Taylor) received her PhD in molecular genetics from the Institute of Child Heath/Great Ormond Street Hospital, at University College London, London, England. She completed her postdoctoral training and an Instructorship at Mount Sinai School of Medicine, New York, where she was awarded a Charles H Revson Biomedical Fellowship.

In 2007, Dr Clelland became a faculty member of the Department of Pathology and the Taub Institute for Research on Alzheimer's Disease and the Aging Brain at Columbia University Medical Center. Upon joining Columbia, she was awarded a National Institutes of Health KL2 Mentored Career grant through the Columbia Clinical and Translational Science Award, and under the auspices of this award she completed a MS in Biostatistics, in the Patient Oriented Research Track. She has since received further grants from the National Institute of Mental Health, the National Institute of Aging, the BrightFocus Foundation and the Stanley Medical Research Institute. Most recently, Dr Clelland was the recipient of a Gray Matters at Columbia Fellowship, and she is currently co-investigator on two clinical trials in schizophrenia and schizoaffective disorder, funded by the Stanley Medical Research Institute.


Research Summary:

Understanding the molecular basis of neuropsychiatric diseases and novel treatment targets.
From study of patients with neuropsychiatric illnesses, including schizophrenia and bipolar disorder, we have identified biological disturbances in the periphery, which we believe reflect the CNS and can thus provide a source to pinpoint primary pathological changes that contribute to the etiology of, and susceptibility to disorders including schizophrenia, bipolar disorder and Alzheimer's disease. My research program focuses on investigating the molecular genetic pathways leading to these peripheral abnormalities, aiming to understand susceptibility and illness progression, as well as to identify treatment targets. Some examples of how we are then translating our biological findings to test novel therapeutic approaches are as follows:

Targeting a Peripheral Deficit of Tetrahydrobiopterin (BH4) in Schizophrenia, Schizoaffective Disorder, and Bipolar Disorder. BH4 is a vital cofactor required for neurotransmitter synthesis, and our group reported a deficit of plasma biopterin (a measure of BH4) in psychiatric disorder patients. We have more recently found evidence for genetic association in psychiatric patients with a very interesting candidate gene (GCH1, which encodes the enzyme that catalyzes the rate-limiting step in BH4 biosynthesis), and my lab is investigating how dysregulation of GCH1 contributes to the BH4 deficit and also, in collaboration with researchers at the Nathan Kline Institute, whether some mood stabilizing drugs function via regulation of GCH1 and BH4 synthesis. Translating these exciting findings, and in collaboration with Dr. Jeffrey Lieberman, Chair of Psychiatry at CUMC, and Director of New York State Psychiatric Institute, we are testing whether alleviation of the BH4 deficit via treatment with a synthetic BH4 supplement (6R-BH4), may give rise to an improvement of positive and negative symptoms, and neurocognitive deficits in patients with schizophrenia and schizoaffective disorder.

Targeting Peripheral Elevation of Proline in Schizophrenia.
Proline is a precursor of the neurotransmitter glutamate, is a neuromodulator at glutamatergic synapses and has a genetic link with schizophrenia through the 22q11 PRODH gene. We recently found that over 26% of an inpatient schizophrenia sample was hyperprolinemic, meaning that these patients exhibited high levels of fasting plasma proline. Elevated CNS proline, which reflects that of the periphery, has been shown to detrimentally impact cognition in both hyperprolinemia type-I patients and patients with 22q11 deletion syndrome, and also in a hyperprolinemic mouse model of schizophrenia. My lab is now investigating the molecular basis of hyperprolinemia in schizophrenia, and working to identify new compounds that regulate PRODH gene expression, and thus can target the hyperprolinemia found in over one quarter of patients tested.

The Role of miRNA pathway dysregulation in Human Tauopathies. My lab is also interested in the potential role of miRNA pathway dysregulation in the etiology of neurodegenerative tauopathies. Using a murine model of tauopathy, plus tissue from human Alzheimer's disease (AD) and frontotemporal dementia (FTD), and healthy aged-matched control brain tissue, and techniques including global miRNA profiling, quantitative RT-PCR, and in situ hybridization, we are investigating the role of miRNAs in the etiology of these devastating diseases.


Representative Publications

Vitamin D insufficiency and schizophrenia risk: evaluation of hyperprolinemia as a mediator of association. Clelland JD, Read LL, Drouet V, Kaon A, Kelly A, Duff KE, Nadrich RH, Rajparia A, Clelland CL. Schizophr Res. 2014 Jun;156(1):15-22. doi: 10.1016/j.schres.2014.03.017. Epub 2014 Apr 29. PMID: 24787057 PMCID: PMC4044915

Clelland CL., Read LL., Panek LJ., Nadrich RH., Bancroft C., Clelland JD. Utilization of Never-Medicated Bipolar Disorder Patients in the Development and Validation of a Peripheral Biomarker Profile. PLoS One (2013) 8(6): e69082. PMID:23826396 PMCID: PMC3691117

Liu L., Drouet V., Wu J.W., Witter M.P., Small S.A., Clelland C., Duff K. Trans-synaptic Spread of Tau Pathology in vivo. PloS One (2012) 7(2): e31302. PMID: 22312444 PMCID: PMC3270029

Clelland CL, Read LL, Baraldi AN, Bart CP, Pappas CA, Panek LJ, Nadrich RH, Clelland JD. Evidence for association of hyperprolinemia with schizophrenia and a measure of clinical outcome. Schizophrenia Research (2011) Sep;131(1-3):139-45. PMID: 21645996 PMCID: PMC3161723

Clelland Taylor CL and Clelland JD. miRNAs in Neurodegenerative Disorders. Advances in Neurology: Genomics, Proteomics and the Nervous System. Springer Publishers, New York. Springer, New York; 1st Edition (2010) December 6:445-454.

Richardson MA, Read LL, Clelland JD, Reilly MA, Clelland, Taylor CL. Analysis of Plasma Biopterin Levels in Psychiatric Disorders Suggests a Common BH4 Deficit in Schizophrenia and Schizoaffective Disorder. Neurochemical Research (2007) Jan;32(1):107-13.

Richardson MA, Read LL, Clelland, Taylor CL, Reilly MA, Chao HM, Guynn RW, Suckow R, and Clelland JD. Evidence for a Tetrahydrobiopterin Deficit in Schizophrenia. Neuropsychobiology (2005) 52:190-201.




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