Research Abstract

I am an Assistant Professor at the Pathology Department at Boston Children’s Hospital and Harvard Medical School. I have established my lab on June 1st 2019, where I will study folate sensing and homeostasis in cells, in the whole-organism and in tumors. Folate is 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 my ability to reliably detect folate by liquid chromatography/mass spectrometry (LC/MS), my CRISPR/Cas9 screen results and experience with individual gene knockouts, my expertise in mouse work, and my strong molecular biology and signaling background, I aim to use genetic perturbations, biochemical assays, molecular biology, metabolite profiling and advanced cancer mouse models for a comprehensive study of folate homeostasis at the cellular and the whole-organism levels, in physiologic and pathologic conditions. I will investigate folate utilization by various cell types and tissues and explore the cancer-specific survival mechanisms of folate-deprived cells in culture and in vivo. I will continue my work on the novel folate utilization regulators I characterized in my postdoctoral work, and will target them in vivo to allow for physiological assessment of our findings. The longterm goals of my work 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.