Boston Children's Hospital
In my lab, we apply mass-spectrometry to address biological questions in cancer metabolism, and a major part of our work focuses on technology and method development. Cancer metabolism is a rapidly growing field within the cancer biology scientific community. Within this field, one-carbon metabolism is particularly interesting due to its central role in several vital metabolic pathways. One-carbon metabolism requires folate, an enzymatic cofactor that is known for its key role in RNA and DNA production. While folate is a key cofactor essential for all living cells and is a targetable vulnerability in cancer cells, our understanding of its homeostasis and usage control is rudimentary. Using our ability to reliably detect folate by mass spectrometry, our experience with CRISPR/Cas9-based screens and individual gene knockouts, our mouse work, and strong molecular biology and biochemistry work, we aim to use genetic perturbations, biochemical assays, molecular biology and metabolite profiling for a comprehensive study of folate homeostasis at the cellular and the whole-organism levels. We investigate folate utilization by various organs and explore the cancer-specific survival mechanisms of folate-deprived cells in culture and in vivo. In addition, we apply preclinical mouse models to study the role of the histidine degradation pathway in the response of cancer cells to the chemotherapy methotrexate. The long-term goals of the Kanarek lab are (i) to significantly improve anti-cancer chemotherapy through the development of our understanding of folate metabolism and the identification of targetable proteins in folate sensing, metabolism and whole-body homeostasis, and (ii) to characterize folate regulation pathways relevant for healthy individuals as well as patients that suffer from folate deficiency related disorders.
Boston, MA 02115