Duke Scholars in Genomic Medicine
The Duke Scholars in Genomic Medicine program was created to provide seed money for research projects that are translational and genomic in nature. Projects within the program focus on the development and application of genomics and proteomics and other tools to improve the prediction, prevention and treatment of human disease for individuals and populations.
Projects are directly linked to the delivery of predictive, preventive and personalized healthcare to individuals and populations. Preference is given to those projects likely to impact human health in the near-term -- generally within five years.
2005-2006 Projects
Team:
David Seo, MD
Kristin Newby, MD
John Michon, MD
Jennifer Clark, PhD
Identifying Novel Biomarkers Predictive for Development of Acute Coronary Syndromes
The central hypothesis of the project is that by studying the gene expression profiles of peripheral blood mononuclear cells (PBMC' s) from patients that will develop ACS, we will be able to identify novel biomarkers that will enable us to predict the development of ACS and learn more about the biology of vulnerable plaques. We will use proven statistical methodologies to identify novel biomarkers in the form of differentially expressed genes and to construct prognostic models combining clinical and genomic information that could be used by clinicians. We have assembled a multidisciplinary team that is well equipped to complete this project and extend it for future research. Finally, we have incorporated industry participation to develop a clear path for commercialization of the results of this project. The information generated by this project will be invaluable for learning more about the biology of the elusive vulnerable plaque and may lead to new tools and therapies improve outcomes in ACS.
Team:
Doug Tyler, MD
Francis Ali-Osman, DSc
Jennifer Clarke, PhD
Joe Nevins, PhD
Pharmacogenetics of Regional Melanoma Therapy
Regional failure in patients with extremity melanoma is a significant problem. Aggressive therapy in the form of amputation suggests that 25-35% of these patients may have disease confined to the extremity. Regional therapy to date shows marked responses but is associated with moderate toxicity and frequent recurrences. There are currently several treatment several treatment strategies that could be utilized in the context of regional therapy that may help improve the efficacy of this form of therapy. These range from new dugs, to inhibitors of drug resistance proteins, to novel targeted therapies. The hypotheses of our group is that global gene expression profiling, in contrast to a detailed analysis of a single gene, will provide a significant clinically relevant measure of the complex genetic alterations underlying the sensitivity or resistance of melanoma to chemotherapy and help guide novel therapeutic strategies.
Team:
Ashley Chi, MD, PhD
Tom Ortel, MD, PhD
Sayan Mukherjee, PhD
Richard Becker, mD
Jogin Wu, PhD
Genomic Strategies to Identify Patients at Hugh Risk for Recurrent Thrombosis
Recurrent venous thromboembolism (VTE) will occur in ~30% of patients with spontaneous VTE after completion of a standard course of anticoagulant therapy (6-12 months) and warrant an extended period of anticoagulant therapy to prevent recurrence. But it is still very difficulty to identify VTE patients at risk for recurrence to deliver the long-term treatment. Certain hypercoagulable states and the presence of residual thrombus on follow-up imaging studies identify patients at higher risk for recurrence, but these strategies appear to identify only a subset of patients with antiphospholipid syndrome, an antibody-mediated thrombotic disorder with a high risk for recurrent thromboembolism, from patients with VTE who do not have antiphospholipid antibodies. We propose to extend this initial observation, which is focused on a subset of patients with VTE, to the larger population of all patients with spontaneous VTE, by 1) identifying gene expression profiles that define the risk for recurrent thromboembolism in patients with a venous thromboembolic event; and 2) defining the gene signature predictors to identify patients at risk for recurrent thrombosis and validate the clinical utility of these genes with quantitative polymerase chain reaction assays.
Team:
John Chute, MD
Joseph Nevins, PhD
Development of a Molecular Signature for Radiation Injury
In light of the magnitude of risk for a nuclear or radiobiologic-terrorist event in the US and the limitations of current tools to estimate radiation exposure, novel technologies can and should be applied to develop more rapid and accurate biodosimetry screening tests. We propose that high throughput gene expression analysis and computational tools have the capacity to identify patterns of molecular changes which occur within human tissues following radiation exposure. Since hematopoietic cells are highly sensitive to radiation effects, we propose that development of a validated panel of "radiation response" genes within circulating hematopoietic cells could be translated into a rapidly applicable diagnostic screening test.
Our group has expertise in the study of radiation effects on hemmatopoietic progenitor cells and has utilized the application of genomic analyses to identify genes predictive of prognosis within several types of cancers as well as genes that predict patient response to chemotherapy. We believe that a similar strategy can be successfully applied to determine which genes will predict different levels of radiation exposure and possibly allow stratification of victims based upon their genomic profile. Once we have generated molecular signatures that can predict different levels of radiation exposure, we will incorporate the key core genes from each signature into the development of a quantitative RT-PCR based assay that has the potential to dramatically improve our national capacity to respond to a radiation or nuclear terrorist attack. More broadly, these studies can facilitate the discovery of the critical pathways that regulate human response to ionizing radiation and, if successful, will help position Duke University as a research center of excellence in biodefense research. In keeping with these broad objectives, the specific aims of this project are to 1) develop a molecular signature of radiation injury; and 2) develop a molecular signature of human radiation injury.