My work focuses on the development of novel and emerging technologies and
applying these to cancer genomic analyses. Our group was the first to apply mass-spectrometric genotyping to interrogate known oncogene mutations in tumor samples- a technology that was more sensitive, faster, and substantially cheaper than current sequencing approaches. We published this technology -OncoMap- and its
associated informatics approaches to rapidly profile cancer specimens. In 20016, we established the Center for Cancer Genome Discovery at DFCI. The goal of this center was to harness emerging technologies- like genotyping and massively parallel sequencing, to further our understanding of cancer genomes.Our ability to cost-effectively and sensitively assess targeted cancer genomes revolutionized precision cancer medicine by identifying the right genomic profile and an associated targeted therapy, as well as starting to identify low-level resistance mutations that emerged as a result of the applications of these therapies. Importantly, we optimized these technologies on “real-world” clinical specimens- often small, formalin-fixed,
paraffin embedded material yielding little DNA. Building on this capability, we initiated a large-scale, multi-institutional prospective epidemiology study called Profile. This initiative, a joint venture between Dana-Farber Cancer Institute, Brigham and Women’s Hospital and Boston Children’s Hospital, was launched in 2011 and offered CLIA-grade genomic profiling to all cancer patients, regardless of type, grade, stage or age. I also
collaborated with other cancer centers (particularly Asan Medical Center in Korea) to establish genomic profiling efforts at their institutions.
Our group was also the first to apply a hybrid-capture approach to specifically target regions of interest in the genome (in this case, known cancer genes) for analysis using massively-parallel sequencing. We applied this in research projects as well as in our clinical program called Profile. This technology advance enabled characterization of common and rare cancer types to a degree previously unattainable. We also published
several novel algorithms for analysis of this data, as well as technical papers on how to deploy this technology in a clinical space. Most recently, we published an initial landscape of the first ~3700 cancer patients analyzed.
To date, we have profiled over 22,000 cancer patients – one of the largest resources in an academic cancer center in the world. We deposit our results in a central knowledgebase that can be linked to clinical outcomes data and enables ongoing research. I am a contributor to AACR Project GENIE, an international collaboration
of cancer centers to share genomic and clinical data. Going forward, we continue to develop new capabilities and deploy these in the clinical setting- RNA sequencing, circulating tumor DNA detection, viral sequencing; as well as developing new algorithms for detection of structural rearrangements, viral sequences, mutational burden and mutational signatures.