Photo of Naama Kanarek,  PhD

Naama Kanarek, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 919-7352


Naama.Kanarek@childrens.harvard.edu

Naama Kanarek, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Assistant Professor, Pathology, Harvard Medical School
  • Assistant Professor, Pathology, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

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.

Publications

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  • Diray-Arce J, Conti MG, Petrova B, Kanarek N, Angelidou A, Levy O. Integrative Metabolomics to Identify Molecular Signatures of Responses to Vaccines and Infections. Metabolites 2020. PubMed
  • Petrova B, Kanarek N. Potential Benefits and Pitfalls of Histidine Supplementation for Cancer Therapy Enhancement. J Nutr 2020; 150:2580S-2587S. PubMed
  • Maynard AG, Kanarek N. NADH Ties One-Carbon Metabolism to Cellular Respiration. Cell Metab 2020; 31:660-662. PubMed
  • Kanarek N, Petrova B, Sabatini DM. Dietary modifications for enhanced cancer therapy. Nature 2020; 579:507-517. PubMed
  • Kanarek N, Keys HR, Cantor JR, Lewis CA, Chan SH, Kunchok T, Abu-Remaileh M, Freinkman E, Schweitzer LD, Sabatini DM. Histidine catabolism is a major determinant of methotrexate sensitivity. Nature 2019; 559:632-636. PubMed
  • Cantor JR, Abu-Remaileh M, Kanarek N, Freinkman E, Gao X, Louissaint A, Lewis CA, Sabatini DM. Physiologic Medium Rewires Cellular Metabolism and Reveals Uric Acid as an Endogenous Inhibitor of UMP Synthase. Cell 2017; 169:258-272.e17. PubMed
  • Shaul YD, Freinkman E, Comb WC, Cantor JR, Tam WL, Thiru P, Kim D, Kanarek N, Pacold ME, Chen WW, Bierie B, Possemato R, Reinhardt F, Weinberg RA, Yaffe MB, Sabatini DM. Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition. Cell 2018; 158:1094-1109. PubMed
  • Horwitz E, Stein I, Andreozzi M, Nemeth J, Shoham A, Pappo O, Schweitzer N, Tornillo L, Kanarek N, Quagliata L, Zreik F, Porat RM, Finkelstein R, Reuter H, Koschny R, Ganten T, Mogler C, Shibolet O, Hess J, Breuhahn K, Grunewald M, Schirmacher P, Vogel A, Terracciano L, Angel P, Ben-Neriah Y, Pikarsky E. Human and mouse VEGFA-amplified hepatocellular carcinomas are highly sensitive to sorafenib treatment. 2018; 4:730-43. PubMed
  • Kanarek N, Grivennikov SI, Leshets M, Lasry A, Alkalay I, Horwitz E, Shaul YD, Stachler M, Voronov E, Apte RN, Pagano M, Pikarsky E, Karin M, Ghosh S, Ben-Neriah Y. Critical role for IL-1β in DNA damage-induced mucositis. Proc Natl Acad Sci U S A 2018; 111:E702-11. PubMed
  • Kanarek N, Ben-Neriah Y. Regulation of NF-κB by ubiquitination and degradation of the IκBs. Immunol Rev 2016; 246:77-94. PubMed
  • Duan S, Skaar JR, Kuchay S, Toschi A, Kanarek N, Ben-Neriah Y, Pagano M. mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR. Mol Cell 2018; 44:317-24. PubMed
  • Kanarek N, Horwitz E, Mayan I, Leshets M, Cojocaru G, Davis M, Tsuberi BZ, Pikarsky E, Pagano M, Ben-Neriah Y. Spermatogenesis rescue in a mouse deficient for the ubiquitin ligase SCF{beta}-TrCP by single substrate depletion. Genes Dev 2018; 24:470-7. PubMed
  • Kanarek N, London N, Schueler-Furman O, Ben-Neriah Y. Ubiquitination and degradation of the inhibitors of NF-kappaB. Cold Spring Harb Perspect Biol 2018; 2:a000166. PubMed
  • Zach N, Kanarek N, Inbar D, Grinvald Y, Milestein T, Vaadia E. Segregation between acquisition and long-term memory in sensorimotor learning. Eur J Neurosci 2019; 22:2357-62. PubMed
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