CLINICAL RESEARCH PROGRAMS:
Prevention and Treatment Research Program in the Division of Infectious Disease
The goals of the HIV Prevention and
Treatment Research Program (HPTRP)(Magdalena Sobieszczyk, principal investigator, and
Michael Yin, co-investigator) are to set the standards of care for people living
with HIV and to help speed the development of an effective vaccine to prevent
HIV infection. The program works toward these goals by engaging the community
and conducting clinical studies within the Division of Infectious Diseases at
the Columbia University Medical Center. The HPTRP participates actively in
studies sponsored by three NIH-funded networks: the Adult AIDS Clinical
Trials Group (AACTG), and the HIV
Vaccine Trials Network (HVTN). The HPTRP also supports pharmaceutical
studies. There are opportunities for fellows and residents to participate in all
aspects of HIV/AIDS clinical trials.
The AACTG is the largest
NIH-sponsored HIV clinical trials organization and plays a major role in
defining the standards of care for treatment of HIV infection and opportunistic
diseases related to HIV/AIDS around the world. We provide a wide range of
treatment studies four areas of focus (1) end organ disease and inflammation,
(2) HIV reservoirs and viral eradication (3) hepatitis, (4)
The HVTN is an NIH-sponsored international network that was
designed to facilitate the process of testing preventive vaccines against
HIV/AIDS. The New York City HIV Vaccine Trials
Unit is a collaboration between the Columbia HPTRP and Project ACHIEVE (AIDS Community Health
Initiative En route to a Vaccine Effort) which is part of the New York Blood
Koblin, PhD, principal investigator). The New York City HIV Vaccine Trials
Unit supports a large number of HVTN-sponsored preventive vaccine trials,
studies investigating combination prevention approaches, as well as a behavioral
interventions among high risk individuals. Past and current fellows have
conducted HIV prevention research projects with investigators in the Vaccine
HIV Center for Clinical and Behavioral Studies
Founded in 1987 and continuously supported by a major grant from the National Institute of Mental Health, the HIV Center for Clinical and Behavioral Studies serves as a national and international hub for a network of research activities and community outreach. Research focuses on the intersection of HIV infection, gender, and sexuality; treatment strategies for infected populations; and innovative dissemination of scientific findings. More than one hundred researchers, clinicians, and support staff sustain the work of the center. Affiliated research is conducted through more than two dozen individual studies headed by leading investigators from various disciplines, including psychology, psychiatry, public health, anthropology, sociology, and social work. The center also works with a broad range of HIV-infected and HIV-affected populations and are committed to responding to the needs of underserved populations.
The Division of Infectious Diseases maintains active collaborations with faculty members from the Mailman School of Public Health in the Departments of Epidemiology and Sociomedical Sciences
HOSPITAL EPIDEMIOLOGY AND INFECTION PREVENTION RESEARCH
Center for Interdisciplinary Research to Prevent
CIRI aims to prepare biomedical researchers and others in interdisciplinary research
with a focus on the prevention and control of antimicrobial resistance. Under
the leadership of Elaine Larson, PhD, RN and Lisa Saiman, MD, the center has
implemented a core program and curriculum to prepare biomedical researchers to
conduct interdisciplinary research. The center also funds several demonstration
projects designed to rationalize antimicrobial use and reduce antimicrobial
resistance. CIRI offers a tremendous resource for pre- and postdoctoral fellows who are
interested in true interdisciplinary research. The framework for CIRAR
integrates health and risk communication, economics, informatics, epidemiology,
and health services with the basic research and disciplinary expertise of its
Recently, CIRI has awarded funding
to three of our trainees conducting research on antimicrobial resistance: Jennifer
Miko and Stephanie
Hospital Epidemiology and
Antimicrobial Utilization, Resistance, and Stewardship
The Division of Infectious Diseases
is actively involved in hospital epidemiology and antimicrobial
stewardship at NewYork-Presbyterian Hospital. These programs are linked to
numerous ongoing clinical research projects focusing on healthcare-associated
infections and antimicrobial resistance, as well as outcomes research evaluating
the impact of interventions in infection prevention and antimicrobial
stewardship. Ongoing research projects include evaluations of specific
antimicrobials such as polymyxin B and daptomycin, evaluations of
multidrug-resistant gram-negative bacilli including those producing Klebsiella pneumoniae carbapenemase (KPC), and severity criteria and
outcomes of patients with Clostridium difficile infections. Past and
current fellows have engaged in many of these clinical research projects with
mentoring from Drs. Yoko Furuya, Christine Kubin, and Lisa Saiman.
TRANSPLANT INFECTIOUS DISEASES RESEARCH
The active transplant
infectious diseases service presents many opportunities for collaborative
and multidisciplinary research projects. Past and ongoing clinical research
projects aim to, for example, develop new tools for diagnosis and treatment of
multi-drug resistant infections in immunocompromised adults in the pre and
Past and current fellows have engaged in mentored research
in the area of transplantation infectious diseases: Jennifer Horan, Stephanie
Pouch and Claire
The Columbia Center for Translational Immunology (CCTI) at Columbia University Medical Center is a multi-departmental, multidisciplinary research center aimed at optimizing translation of advances in basic immunology from the laboratory to the clinic, understanding immunological diseases and events in humans and optimizing transfer of information and methodologies to achieve synergy between different disciplines of applied immunology. The CCTI currently consists of three laboratories and three cores, including a Sample Repository, a Human Studies Core and a Flow Cytometry Core. CCTI investigators have expertise at all levels of immunology and transplantation, from molecular biology to large animal and clinical transplantation studies. Extensive collaborations are carried out among these laboratories and between clinicians and basic scientists, including close interactions with the transplant physicians and surgeons in the Columbia Transplant Initiative.
The mission of the CCTI is to accelerate translation of basic advances in immunology into new clinical therapies for immune diseases by creating a center that: 1) Fosters “horizontal” integration of information and advances between immunological disciplines and "vertical" integration between scientists and clinicians; 2) Trains a new generation of scientists and clinicians with the skills to lead the translation of future advances in immunology into clinical therapies.
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CLINICAL RESEARCH PROGRAMS:
The International Center for AIDS Care and Treatment Programs (ICAP): http://icap.columbia.edu/
together diverse initiatives aimed at addressing the HIV/AIDS epidemic, the
International Center for AIDS Care and Treatment Programs (ICAP) focuses on
service delivery, research, and training/education in resource-limited settings.
Faculty and staff provide support in program development, clinical issues,
administration, training, monitoring and evaluation, and research endeavors. The
program draws upon the broader resources of the Mailman School of Public Health,
as well as those of Columbia University, to fulfill its mission. As a center
within the school, and as part of the Columbia health sciences campus, ICAP is
committed to participating in the life of the academic medical institution and
to providing training opportunities for students, house staff, and fellows.
ICAP offers postdoctoral trainees access to large databases in order to
develop, conduct, and analyze cohort studies while addressing infectious disease
epidemiology issues of global importance.
ICAP provides support and
assistance to international partners and clinical facilities through these
programs and initiatives:
With its roots in comprehensive, family-focused
HIV services, ICAP is known for capacity building and for its innovative,
effective, and ethical programs that are implemented in the most challenging
resource-limited settings. ICAP is also known for its collaborative and
supportive approach to strengthening government health systems and local
partners’ capacity to deliver quality health services.
To date, ICAP has worked to address major public health challenges and the
needs of local health systems in more than 3,300 sites across 21 countries.
- Cameroon, Côte d’Ivoire,
Ethiopia, Kenya, Lesotho
- Malawi, Mali, Mozambique, Rwanda
- Tanzania, The
Democratic Republic of the Congo
- Uganda, Zambia
University of KwaZulu-Natal, IACTU, and CAPRISA in South
The division maintains a
strong collaborative relationship with the Mandela School of Medicine,
University of KwaZulu-Natal in Durban, South Africa. The projects currently in
place include collaborations with the Centre for the AIDS Program of
Research in South Africa, CAPRISA (Professor Salim Abdool
Karim, principal investigator). CAPRISA was created in 2001 and formally
established in 2002 under the NIH-funded Comprehensive International Program of
Research on AIDS (CIPRA) by five partner institutions; University of
KwaZulu-Natal, University of Cape Town, University of Western Cape, National
Institute for Communicable Diseases, and Columbia University. CAPRISA's goal is
to develop and undertake research that contributes to the understanding of HIV
pathogenesis and epidemiology, as well as to build local research infrastructure
and to provide training through research fellowships for young investigators
from South Africa and the United States. To achieve this goal, CAPRISA conducts
research in four main Scientific Programs: HIV Pathogenesis and vaccines, HIV
and TB treatment, Microbicides, and Prevention and Epidemiology.
One of the projects initiated by the CAPRISA research team is an NIH-funded
acute infection study evaluating the clinical, immunological, and viral factors
during acute and early HIV-1 subtype C infection. A large cohort of HIV-1
negative high-risk women has been enrolled and followed in this observational
The Columbia University International Family AIDS Program (IFAP), La
Romana, Dominican Republic
The Columbia University
International Family AIDS Program (IFAP), established in 1999 by Dr. Stephen
Nicholas, has supported AIDS-focused global health rotations for pediatric
residents in La Romana, Dominican Republic (DR). The program is a collaborative
effort with Clinica de Familia MIR, a comprehensive family AIDS clinic in La
Romana. IFAP is a non-profit organization that supports clinical services, and
research, education and training. Program activities focus on improving direct
care and treatment as well as preventive health education and services for TB
and HIV-infected women, children and families and other vulnerable populations
in the Dominican Republic.
HIV Treatment Centers in the Dominican Republic
Drs. Karen Brudney and Barbara Taylor have a long-standing relationship with
two non-governmental organizations, the Instituto Dermatologico y Cirugia de Piel
Dr. Huberto Bogaert Diaz and the Clinica
Profamilia Evangelina Rodriguez which provide specialty HIV care and HIV
prevention services in Santo Domingo, Dominican Republic. This collaboration
supports a longitudinal cohort that examines treatment outcomes and the
development of antiretroviral resistance among people living with HIV on
BASIC SCIENCE RESEARCH OPPORTUNITIES
Scott Hammer, MD
The Retrovirology Research Laboratory has been established to support HIV therapeutic and vaccine clinical trials with specialized virologic techniques that can be applied to clinical specimens to detect and quantify HIV expression in peripheral blood and tissue compartments, as well as to prepare specimens for HIV-specific immune assays. Dr Hammer's specific interests include HIV drug resistance and new assay development.
Frank Lowy, MD
Dr Lowy's research is focused on the pathogenesis and epidemiology of Staphylococcus aureus infections. Staphylococcus aureus remains a major cause of morbidity and mortality in both hospital- and community-acquired infections. The recent increase in antimicrobial resistance among strains of S. aureus has heightened concern about our limited understanding of the pathogenesis as well as the limited options available for the treatment of these life-threatening infections. Ongoing projects in Dr Lowy's laboratory include (1) identification and characterization of a staphylococcal protein that mediates binding to endothelial cells, (2) demographic and molecular epidemiologic investigation of staphylococcal colonization and disease in populations at high risk of S. aureus infection, (3) bacterial and cellular gene expression in murine models of infection, and (4) investigation of the biology of nasal colonization with S. aureus.
David Fidock, PhD
Dr. Fidock’s specialty Malaria drug resistance,
chemotherapy, pathogenesis, cell development. "A major focus of our group
is to elucidate the molecular basis of chloroquine resistance (CQR). By genetic
linkage and positional cloning, we earlier identified the pfcrt gene, located
within a chromosomal segment tightly linked to CQR, which encodes a novel
10-transmembrane transporter located on the intra-erythrocytic parasite’s
digestive vacuole. Using allelic exchange techniques, we recently proved that
mutations in this gene, identified in drug resistant parasites from around the
globe, are sufficient to confer CQR to CQ-sensitive parasites. Current work
focuses on understanding the contribution of the individual mutations to CQR,
determining their impact on parasite resistance to other antimalarials, and
investigating the biochemical basis of CQR. We are also developing animal models
to explore the role of pre-existing immunity on host clearance of drug-resistant
infections. In collaboration with Dr. Myles Akabas at AECOM, we are also
investigating the natural transport properties of pfcrt in heterologous cells.
Other studies focus on defining the role of PfATPase6, pfmdr1 and pfnhe in
contributing to parasite susceptibility to artemisinin, quinine and mefloquine.
We are also deeply involved in a major public/private
partnership, funded by the Medicines for Malaria Venture and the NIH, and
including GlaxoSmithKline and several academic partners, that aims to develop
new antimalarial drugs that target fatty acid biosynthesis in the malaria
parasite. Another aspect of our research is to investigate the
molecular basis of how parasitized erythrocytes bind to host endothelium,
enabling them to avoid splenic clearance. A variant antigen family, PfEMP1,
mediates this binding. We are investigating mechanisms of gene regulation that
contribute to this switching of gene expression between different members of
this family and exploring the genetic basis of endothelial receptor specificity.
The fourth area of research focuses on the
digestive vacuole, the site of CQ action. Specifically, we are examining which
ER or Golgi proteins are involved in protein trafficking to this compartment and
using transfection and bio-informatic approaches to define sequence motifs that
direct proteins to this site." Dr. Fidock's Lab Page
Anne-Catrin Uhlemann, MD, PhD
Dr. Uhlemann’s laboratory investigates the evolution of bacterial pathogens such as Staphylococcus aureus and carbapenem-resistant Klebsiella pneumoniae.
S. aureus research: The past decade has witnessed a dramatic increase in Staphylococcus aureus infections acquired from the community. Yet there remains a limited understanding of how these strains spread and subsequently become established and persist within communities. Our research is focused on identifying molecular mechanisms that allow epidemic S. aureus strains such as USA300 to successfully disseminate. This project uses a combined approach of whole-genome comparative sequencing of longitudinally collected samples, genetic manipulation, and functional studies on bacterial adhesion and survival. These molecular studies are informed by ongoing epidemiological studies on S. aureus transmission in the local community. This work has identified a potentially newly emerging S. aureus strain, ST398, which was previously only associated with close contacts to animals. Ongoing studies are aimed at elucidating the molecular mechanisms of its cross-species transfer and current animal-independent spread.
K. pneumoniae infections in transplant recipients: Infections with carbapenem-resistant Enterobacteriaceae (CRE) have emerged as an urgent threat to healthcare, the “category of highest concern” in the 2013 CDC antimicrobial threat report. These multi-drug resistant infections are associated with high mortality. Recipients of solid organ transplantation, in particular liver transplant recipients are at increased risk for CRE infections. While intestinal colonization with CREs has been proposed as a potential risk factor for infections during CRE outbreaks, its actual contribution to infection remains incompletely understood. Moreover, there is a fundamental gap in knowledge on how these antibiotic resistant organisms transition from colonization to infection within affected hosts. We have established a cohort study of patients undergoing liver transplantation in which we aim to investigate the contribution of colonization to subsequent CRE infection. The long-term goal of this project is to elucidate at the bacterial genome level how CRE infections emerge and spread. Understanding these processes is critical to developing intervention and real-time clinical monitoring approaches to limit the impact of CRE infections at an individual and population level.
Jonathan Dworkin, PhD
Dworkin’s lab is interested in how dormant cells of various bacteria (B.
subtilis, M. tuberculosis, and M. luteus) re-initiate growth and we have
identified a well-conserved, eukaryotic-like Ser/Thr kinase that is essential
for these bacteria to exit dormancy in response to muropeptides generated by
growing bacteria. A target of this kinase is Elongation Factor G (EF-G), the
essential GTPase regulating translation, and we are examining how this
phosphorylation changes the activity of this protein. In addition, Dr. Dworkin
is examining the role of this kinase in antibiotic resistance and survival
during stationary phase in B. subtilis, M. luteus and S.
Stephen Goff, PhD
Dr Stephen Goff is the Higgins Professor of Biochemistry and Molecular Biophysics and a professor of microbiology. The central focus of his laboratory for several years has been a detailed genetic analysis of the replication cycle of the Moloney murine leukemia virus (M-MuLV). The major approach has been to create mutations in a cloned DNA copy of the viral genome by site-directed mutagenesis and to determine the effect of the mutations on the viral life cycle after transfer of the altered DNAs into mouse cells in culture. These genetic analyses have defined the functional domains of various viral proteins and the sites of their action on viral nucleic acids. Dr Goff's group has also expressed reverse transcriptase and integrase in bacteria and studied these enzymes biochemically. Recently, they have applied the yeast two-hybrid system to monitor protein-protein interactions between viral proteins, and to identify new host proteins that interact with the gag, pol and env gene products. Other members of the group are interested in the functions of several viral oncogenes, especially the tyrosine kinases v-abl and v-src, and related signal transduction molecules, including the axl/ark receptor kinase; mpl, the thrombopoietin receptor; pdeg, the retinal cGMP phosphodiesterase; and various cytokine receptors. Finally, embryonic stem cell technologies are being used to generate knock out mice deficient in these transduction molecules. For more information, please visit the Goff lab home page.
Vincent Racaniello, PhD
Dr Vincent Racaniello is the Higgins Professor of Microbiology. Research in this laboratory is aimed at understanding the replication and pathogenesis of picornaviruses. These RNA-containing viruses cause a variety of human diseases including paralysis, myocarditis, conjunctivitis, and the common cold. Dr Racaniello's studies focus on the interaction of viruses with cell receptors, translation of the viral genome, and the molecular basis of viral pathogenesis. Dr Racaniello's group has developed a mouse model that is being used to address questions on the pathogenesis of poliomyelitis, such as how poliovirus infection is restricted to specific cell types such as neurons, how the virus spreads in the infected animal, and the basis for the attenuation phenotype of the live poliovirus vaccines. A similar approach has been utilized to establish mouse models for diseases caused by other picornaviruses, including echoviruses, rhinoviruses, and enteroviruses. For more information, please visit the Racaniello lab home page.
Howard Shuman, PhD
Dr Shuman is a professor of microbiology. His group has been studying the interaction between an intracellular pathogen, Legionella pneumophila and human macrophages. His approach has been based on using bacterial genetics to understand complex systems at the molecular level. Dr Shuman's group has identified and characterized a group of Legionella genes called icm genes which are important in formation of the specialized phagosomes which L. pneumophila inhabit. The Icm gene products are absolutely required for intracellular multiplication in eukaryotic hosts but are dispensable for growth on bacteriologic media. In the wild, Legionella and related species probably grow as parasites or endosymbionts in protozoa. Some of the Icm proteins are related to known conjugal and secretion systems in other organisms. Dr Shuman's group is testing the hypothesis that a subset of the icm products are transferred to host cells and directly prevent phagosome–lysosome fusion. In collaboration with the Columbia Genome Center, they have recently begun a complete analysis of the Legionella genome in order to elucidate the genetic basis for intracellular pathogenesis and symbiosis.
The Division of Infectious Diseases has affiliations throughout Columbia University Medical Center. Additional basic-science research opportunities for fellows are available with other faculty in the Department of Microbiology, the Pediatric Infectious Diseases Division, and other divisions and departments within CUMC.