Our long-term research goal is to advance basic scientific findings related to human brain tumors into improvements for our treatment of patients with these cancers. My clinical practice is focused at the MGH, where I devote a portion of my professional effort toward translational clinical activity in an academic environment, performing approximately 150 tumor neurosurgical procedures annually.
The larger portion of my professional effort is laboratory-based research activity focused on the study of malignant brain tumors to gain insight into the molecular genetic alterations that underlie their development, progression and treatment resistance. By understanding the mechanism by which these alterations drive formation of these cancers, therapeutic strategies to exploit this knowledge can be developed to improve outcomes for these patients.
We have made key observations regarding the molecular mechanisms of chemoresistance in human glioblastomas, over the last decade as combined radiation and alkylating chemotherapy temozolomide have become the standard-of-care. Our findings represented the first genomic evidence of mismatch-repair-mediated chemoresistance in any human tumor system, extending a well-established in-vitro model to the clinically relevant human treatment scenario. In the last year, our group has identified a tight linkage between IDH1 mutation in malignant astrocytomas and prolonged survival after surgical resection, a finding which can guide the personalization of therapy for patients with this type of brain tumor.
At the national level, our group performed molecular genetic analyses in the large randomized multi-national clinical trial of temozolomide dosing in glioblastoma, the Radiation Therapy Oncology Group 0525 study (RTOG-0525), contributing to the identification of molecular risk groups that will form the basis for future research on therapies for this disease. We have also participated at the national level on brain tumor committees with the aim to drive further innovation in the design of new clinical trials.