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Overview of Research Focus 

My research program focuses on cancer and rare diseases, and uses large-scale translational genomic, systems biology, and pharmacological studies to interrogate and treat human disease. I have led multiple collaborative groups with the goal of characterizing and treating disease, and have been successful at developing research-based clinical trial studies that positively impact patient care. By integrating broad disciplines centered on translational sciences, we will promote innovative scientific exploration and enable scientists to tether clinically impactful results to the enhancement of patient care. A subset of my key research initiatives, further detailed in our publications, include;

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Matching Biological Basis of Disease to Treatment Strategies for Translational ResearchMy focus on translational research comes from an understanding that we need to bring cutting edge science techniques to the clinic now. We need new strategies to better personalize drug therapies, and better approaches to combat drug resistance. Systems biology can be the common platform for classifying disease states, biological networks, and drug response. By finding the gene expression profiles for each of these features, we can identify those profiles that “match” disease to biology to drug and more effectively treat patients.

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Disease Prevention and Early Intervention Strategies. Despite the uptick in rates of discovery for diseases, such as rare and infectious diseases, there has been no corresponding uptick in drug discovery to treat them. Without mechanisms in place to rapidly identify compounds likely to be safe and effective for treating these novel diseases, healthcare systems risk sub-optimal patient care. Our published research shows that we can use genomic analysis to link the right drugs to individual patients. We currently utilize novel genomic approaches to provide individualized and accurate assessments for unknown or novel diseases and high-risk populations.

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Computational Tools for Genomic Studies. A significant component of my research program is to develop novel computational and systems biology tools and resources in order to interrogate biologically relevant signaling events in human disease. Specifically, in close collaborations with my statistician and mathematician colleagues, I have contributed to the development of algorithms critical for distilling genomic and experimental data to biologically and therapeutically meaningful information.

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Combating Tumor Subclone Heterogeneity. Breast and ovarian cancers are comprised of heterogeneous populations of tumors cells characterized by mutations that distinguish each cell subpopulation from one another. During treatment, tumor “subclones”, defined as a set of unique cells within a tumor, follow unique evolutionary and resistance trajectories. Using computational tools to organize this complex variation, we will develop a new class of systems models that define subclone evolution and acquisition of oncogenic phenotypes during treatment in order to identify key chemo-resistant cell states within our patient cohorts. These mechanistic models will identify points of vulnerability for drug targeting. Our clinical trials will be aimed at blocking transition of tumors to a resistant state by blocking critical resistant phenotypes.