BBS Faculty Member - Naama Kanarek

Naama Kanarek

Assistant Professor

Boston Children's Hospital
Department of Pathology, Enders 3108
300 Longwood Ave
Boston, MA 02115
Tel: 617-919-7352
Email: naama.kanarek@childrens.harvard.edu
Visit my lab page here.



The Kanarek Laboratory is interested in folate metabolism. It is surprising that this essential vitamin, so famous for its key role in development, hematopoiesis and cancer progression, is still a mystery when it comes to its cellular and whole-body sensing and homeostasis.
The Kanarek lab applies genetic perturbations, biochemical assays, molecular biology, functional genomic screens, and metabolite profiling by mass spectrometry in cell-culture systems and in vivo to study basic folate biology including folate metabolism, folate-related signal transduction, the oncogenic role of folate and folate homeostasis in normal physiology and pathological conditions.

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 cancerspecific 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.



Last Update: 8/5/2020



Publications

For a complete listing of publications click here.

 


 

Maynard A and Kanarek N*; NADH ties 1-Carbon Metabolism to cellular respiration. Cell Metabolism, 2020 Apr 7;31(4):660-662. doi: 10.1016/j.cmet.2020.03.012. *corresponding
author.

Kanarek N*, Petrova B and Sabatini DM; Dietary modifications for enhanced cancer therapy. Nature, 2020, 579, 507–517. doi: 10.1038/s41586-020-2124-0.
Epub 2020 Mar 25. *corresponding author.

Kanarek N, Keys HR, Cantor JR, Lewis CA, Chan SH, Kunchok T, Abu-Remaileh M, Freinkman E, Schweitzer LD and Sabatini DM; Histidine catabolism is a major determinant of methotrexate sensitivity. Nature 2018 Jul;559(7715):632-636. doi: 10.1038/s41586-018-0316-
7. Epub 2018 Jul 11.

Cantor JR, Abu-Remaileh M, Kanarek N, Freinkman E, Gao X, Louissaint Jr. A, Lewis CA, Sabatini DM; Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an
Endogenous Inhibitor of UMP Synthase. Cell 2017 169 (2): 258-272.e17



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