MOLECULAR GENETIC TECHNIQUES FOR PRECISION DIAGNOSIS
NOVEL SEQUENCING TECHNOLOGY
COPY NUMBER VARIATION AND DNA METHYLATION
DEVELOPMENT OF COST-EFFECTIVE GENETIC INTERPRETATION
Applying molecular genetic techniques to the diagnosis and treatment of human neoplasia. Diagnostics and clinico-pathologic evaluation of non-small cell lung cancer, including the description of morphologic correlates of EGFR, MET, and KRAS mutation and ALK and ROS1-rearranged tumors in a large cohort of patients. We continue to work on analyzing other genetic subtypes with targeted therapies in development, including MET exon 14 skipping variants, and NTRK and RET fusions.
We have also dedicated significant resources to developing novel sequencing technologies to identify genetic alteration in cancer. We have made major strides in bringing high-throughput genotyping tools into the clinic and been involved in national consortia and large multi-center clinical trials such as NCI-MATCH. We have developed the Anchored Multiplex PCR methodology for NGS-based detection of gene fusions and gene mutations. These assays have been implemented at MGH and across many labs world-wide. Most recently we have developed and validated clinical assays for detection of circulating tumor DNA.
My other major research interest involves the study of copy number variation and DNA methylation in the human genome. As a postdoctoral research fellow in the laboratory of Dr. Charles Lee at BWH, we used microarray-based comparative genomic hybridization (array CGH) to study normal human populations. We found unexpected large variations in genome segment copy number between individuals, termed large-scale copy number variants or CNVs. Our research effort continues to explore the detailed genomic structure of these CNVs, and to assess their role in disease association. In addition, we have developed highly-multiplexed probes in situ genetic genomics. We have used microarray, methylation-specific PCR, and NGS to analyze DNA methylation patterns in cancer.
Interpretation of molecular findings and sustainability are major challenges in the field of precision medicine. We have helped develop approaches to reporting clinical variants to allow for accurate and cost-effective interpretation of genetic alterations in tumors, including most recently the use of artificial intelligence. Financial sustainability of tumor genotyping in the clinic has also been a long-term focus of our group.