Geoffrey S. Ginsburg, MD, PhD
Research Interests
Overview
Dr. Ginsburg’s research activities are largely multidisciplinary in keeping with the multi- and interdisciplinary nature of the Institute for Genome Sciences & Policy (IGSP). His strategy has been to create a novel environment of participation and achievement that is attractive to Duke investigators from a variety of disciplines who share an interest in translating genomic information to inform clinical decision making. The Center for Genomic Medicine (CGM) has focused on projects in areas of clinical equipoise and where the use of genetic and genomics in medical decision making will have major impact – i.e., with life or death outcomes or where outcomes will have significant economic consequences. The CGM has forged robust collaborative teams that enable CGM to simultaneously address critical issues in cancer, cardiovascular disease, infectious disease, and primary care.
Cancer Genomic Medicine Programs:
Clinical utility of genomic based risk stratification in lung cancer guiding therapeutics: In collaboration with Joseph Nevins, PhD, Anil Potti, MD, and David Harpole, MD, this project’s goal is to initiate a ‘first of its kind’ prospective clinical trial to assess the utility of a microarray based predictor for classifying risk and assigning patients with Stage I lung cancer to usual care or genomics-guided adjuvant chemotherapy. This design represents a paradigm shift that will characterize CGM studies going forward – trials that test the ability of a genomic predictor to improve therapeutic outcomes. The trial will be sponsored by the CALGB and is set to commence in late 2008.
Clinical utility of genomic predictors of response to cytotoxic chemotherapeutic agents in breast and lung cancer: This project in collaboration with Dr. Nevins’ and Potti’s groups is also aimed at a series of clinical trials using a novel series of microarray based predictors, in this case to forecast the responses and resistance to conventional, FDA-approved, cytotoxic chemotherapies in the context of a “proof of concept” phase II clinical trial in the breast neo-adjuvant setting at Duke. Three studies – one in the breast cancer neoadjuvant setting (funded by the DOD, Kelly Marcom, MD, PI) and the others in lung cancer neoadjuvant therapy and for advanced disease (funded by industry, Drs Anil Potti, Neal Ready, and Michael Kelly, PIs) – were begun in 2007.
Cardiovascular Genomic Medicine:
Predicting near-term events in acute coronary syndromes: The goal of these studies is to develop novel clinical/molecular risk predictors that will detect individuals at high risk for developing an acute coronary syndrome within one year -- in other words, to detect “the vulnerable patient.” Within Duke’s unique CATHGEN resource (developed by Drs William Kraus and Chris Granger) we have identified a series of patients who were stable during their index catheterization yet who went on to develop ACS within one year. The hypothesis is that genomic and molecular analyses of blood based biospecimens from these patients will yield a novel multi-dimensional risk predictor for the near term event.
Predicting Response and Resistance to Cardiovascular Therapies: The goal of these studies is to utilize genetic and genomic tools to develop robust pharmacogenomic predictors of response and adverse events for medications used to treat cardiovascular disease. One series of studies (with Drs Deepak Voora and Svati Shah) utilizes a SNP based approach in the STRENGTH cohort to develop of predictors of response and adverse events to ‘statins’ – cholesterol lowering agents. Deepak Voora MD, is leading a study of aspirin resistance using both the platelet transcriptome and serum proteomics to develop novel signatures predictive of the effects of this important cardiovascular therapeutic.
Infectious Disease and Environmental Genomic Medicine Programs:
Predicting pathogen etiology in the febrile and presymptomatic patient: This project is a collaboration with investigators in the Division of Infectious Disease (Drs. Christopher Woods, Jay Varkey, Aimee Zaas) and the subject of a funded project by DARPA and has as an ultimate goal development of a more precise means of guiding anti-infective therapeutics in the acute care setting using multidimensional genomic signatures. A pilot project is underway that will determine the utility of blood expression profiling to classify the etiology of fever as part of a UO1 funded project (Drs Woods and Vance Folwer, MD, PI). The DARPA program is focused on predicting incipient viral illness using a series of experimental human viral challenge studies. Viral challenges with rhinovirus, respiratory syncytial virus, and influenza have been completed.
Genomic signatures predictive of invasive candidiasis: This project is a collaboration with investigators in the Division of Infectious Disease (Drs Aimee Zaas and John Perfect) and has been jointly funded by the Center for Genomic Medicine and the DID. The project has a goal of developing early and precise prediction of candidemia. Murine models have been developed for invasive candiasis that have been interrogated with various molecular and genomic tools over time. Using microarray analysis of peripheral blood several factors have been identified that are highly sensitive for early detection of infection. Temporal specific factors have also been identified that have been validated in a two cohorts of animals. A longitudinal cohort of high risk patients is being ascertained for validation in human cohorts.
Genomic signatures predictive of environmental exposures: The goal of these studies (funded by RadCCORE and DOE) is to explore the hypothesis that the blood or RNA containing blood components (e.g., monocytes) are physiologic ‘biosensors’ that integrate signals relevant to environmental exposures. IGSP investigators (Drs. John Chute and Holly Dressman) have developed data showing a correlation between blood expression profiles and levels of exposure to ionizing radiation both in a mouse model as well as in patients receive radiation in the course of bone marrow transplantation.
Primary Care Genomic Medicine Programs:
Clinical Genomics in the Outpatient Setting: Dr. Alex Cho in the CGM has initiated a program to disseminate genetic and genomic technologies in the primary care setting at Duke focusing on complex chronic diseases such as diabetes and cardiovascular disease (funded in part by The Duke Endowment). The CGM is collaborating with the Family and Community Medicine Department (Dr. Lloyd Michener) and the Duke University Affiliated Practices (Dr. Scott Joy) to study the clinical utility of genetic variants for type 2 diabetes mellitus on health behaviors and outcomes. The goal is to develop a prototype for health care delivery model for clinical care using genetic information. The project is also a vehicle for educating health care professionals as well as the public about the genetics and genomic applications to human health.
Determining attitudes of patients toward pharmacogenetic testing: For genomic medicine to translate to the clinical environment it is essential that we understand the attitudes, concerns, beliefs and values patients place on genetic testing. The goal of this study (funded by NHGRI) being done collaboratively between CGM (Drs. Susanne Haga and Laura Beskow) and the Center for Genome Ethics, Law and Policy is to develop a robust understanding of attitudes of Durham community residents and patients on genetic and pharmacogenetic testing.
Unique Resources Development:
IGSP Biorepository: The need for well annotated and archived clinical data and biological specimens for multidimensional genomic studies aimed at developing predictive markers has been clear for some time. To fill a much needed gap in Duke’s infrastructure to support genomic medicine studies today and in the future, the CGM has taken the lead to develop an IGSP Biorepository together the DTMI that will become a key component of current and future projects, both in CGM and throughout DUMC.
Clinical Genomics Studies Unit: Designing and executing prospective clinical studies and clinical trials based on genomics is and will be a defining feature for the IGSP and Duke and a core aspect of genomic medicine. To date, and to the best of our knowledge, no genome center in the world has developed a unit dedicated to ‘operational excellence’ in the execution of genome based clinical trials aimed at proving the clinical utility of genomic testing. Housed in the CGM, the IGSP Clinical Genomics Studies Unit (CGSU) is setting the standard for genome based clinical studies and clinical trials and will be the prototype for others to follow. Moreover, this unit is intended as an institutional resource for investigators at Duke that have a strategy and interest in conducting gene- or genomics-based clinical studiies.
Contact Information
Geoffrey S. Ginsburg
Phone: 919-668-6210
2111 CIEMAS
Email
Assistant to Dr. Ginsburg
Rita L. Chambers
Phone: 919-668-6210
2117 CIEMAS