My principal effort at Dana-Farber Cancer Institute (DFCI) and Harvard Medical School (HMS) is in translational research, with a focus on computational cancer genomics, the application of massively parallel sequencing to precision cancer medicine, and resistance to cancer therapeutics. I also have a clinical practice at the Lank Center for Genitourinary Oncology at DFCI. I spend my remaining time devoted to teaching, other administrative tasks, and peer review.
Area of Excellence: My area of excellence is in the emerging field of clinical computational biology. As both a medical oncologist and computational biologist, I am uniquely positioned to lead precision oncology efforts at DFCI. Specifically, I have developed and applied a methodology for the clinical interpretation of whole exome sequencing data from cancer patients for clinical use. This effort, which I presented as an oral abstract at the American Society of Clinical Oncology (ASCO) national meeting (2012) and published in Nature Medicine (2014), has led to clinical trial enrollment and treatment responses for patients who were otherwise refractory to therapy. I have since applied platform to the ongoing CanSeq initiative at DFCI, which will facilitate the assessment of the algorithmâ€™s clinical utility prospectively. Moreover, I am further innovating on these methods through my leadership role in the DFCI Stand Up 2 Cancer prostate cancer dream team project, for which I am generating whole exome and transcriptome data from patient samples to guide treatment selection and infer biological drivers of metastatic disease. This work will serve as the foundation for multiple upcoming manuscripts.
In addition, I am leading efforts to discover genomic mechanisms of response and resistance to multiple therapies across tumor types. This has included the discovery that MEK2 mutations drive clinical resistance to RAF and RAF/MEK combination therapy in metastatic melanoma (Cancer Discovery, 2014), and that ERCC2 mutations confer cisplatin sensitivity in bladder cancers (Cancer Discovery, 2014). More recently, I have expanded these approaches to study response and resistance to targeted and immunological therapies in larger cohorts of prostate, bladder and kidney cancers at multiple time points, which will involve algorithm development to understand tumor cell population shifts during treatment. Finally, I have expanded these approaches to discover genomic mechanisms of exceptional response to immunotherapies, with an initial manuscript in preparation.
Clinical Activities: The rest of my effort is as a medical oncologist seeing genitourinary oncology patients at DFCI.
Administration/Institutional Service Activities: I am focused on improving the user interface for Oncopanel reports generated for every DFCI patient.
Teaching and Educational Contributions: I currently mentor two DFCI computational biologists. I also mentor DFCI medical oncology fellows, and teach a seminar on clinical cancer genomics at the Massachusetts Institute of Technology (MIT).
Overall, I am a physician-scientist active in translational research, patient care, institutional service, and education. These activities occur at DFCI, Brigham and Womenâ€™s Hospital, and the Broad Institute of MIT and Harvard, and are focused mainly through my effort as a clinical computational biologist.