Jason R. Cantor
Massachusetts Institute of Technology
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Publication
Featured researches published by Jason R. Cantor.
Cell | 2017
Jason R. Cantor; Monther Abu-Remaileh; Naama Kanarek; Elizaveta Freinkman; Xin Gao; Abner Louissaint; Caroline A. Lewis; David M. Sabatini
A complex interplay of environmental factors impacts the metabolism of human cells, but neither traditional culture media nor mouse plasma mimic the metabolite composition of human plasma. Here, we developed a culture medium with polar metabolite concentrations comparable to those of human plasma (human plasma-like medium [HPLM]). Culture in HPLM, relative to that in traditional media, had widespread effects on cellular metabolism, including on the metabolome, redox state, and glucose utilization. Among the most prominent was an inhibition of de novo pyrimidine synthesis-an effect traced to uric acid, which is 10-fold higher in the blood of humans than of mice and other non-primates. We find that uric acid directly inhibits uridine monophosphate synthase (UMPS) and consequently reduces the sensitivity of cancer cells to the chemotherapeutic agent 5-fluorouracil. Thus, media that better recapitulates the composition of human plasma reveals unforeseen metabolic wiring and regulation, suggesting that HPLM should be of broad utility.
Cancer Research | 2017
Naama Kanarek; Elizaveta Freinkman; Jason R. Cantor; Monther Abu-Remaileh; Tim Wang; David M. Sabatini
The chemotherapeutic drug methotrexate (MTX) inhibits nucleotide biosynthesis and causes cell death by blocking DNA and RNA production. While MTX has had tremendous success as an anti-cancer treatment and is the subject of nearly a thousand ongoing clinical trials, we do not fully understand why certain cancers are more sensitive to it and why resistance emerges. To study these questions, we used a CRISPR-based genetic screen to identify genes that confer sensitivity to MTX. We identified an enzyme that plays a key role in a metabolic pathway that was not known to be associated with MTX sensitivity. Inhibition of the pathway, either by genetic loss of several genes in the pathway or through nutritional modulations, causes dramatic resistance to MTX in cultured cancer cells. Our results improved our understanding of the cellular response to MTX, and suggest that expression levels of enzymes in the pathway may serve as clinical predictor for MTX response in patients. Citation Format: Naama Kanarek, Elizaveta Freinkman, Jason Cantor, Monther Abu-Remaileh, Tim Wang, David M. Sabatini. Genome-wide CRISPR screen and metabolite profiling reveal a new mechanism of methotrexate sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4988. doi:10.1158/1538-7445.AM2017-4988
Cell | 2014
Yoav D. Shaul; Elizaveta Freinkman; William C. Comb; Jason R. Cantor; Wai Leong Tam; Prathapan Thiru; Dohoon Kim; Naama Kanarek; Michael E. Pacold; Walter W. Chen; Brian Bierie; Richard Possemato; Ferenc Reinhardt; Robert A. Weinberg; Michael B. Yaffe; David M. Sabatini
Nature | 2018
Naama Kanarek; Heather R. Keys; Jason R. Cantor; Caroline A. Lewis; Sze Ham Chan; Tenzin Kunchok; Monther Abu-Remaileh; Elizaveta Freinkman; Lawrence D. Schweitzer; David M. Sabatini
Aiche Journal | 2018
Woo S. Ahn; Wentao Dong; Zhe Zhang; Jason R. Cantor; David M. Sabatini; Othon Iliopoulos; Gregory Stephanopoulos
PMC | 2016
Kuang Shen; Jason R. Cantor; Rachel L. Wolfson; Lynne Chantranupong; Robert A. Saxton; Sonia M. Scaria; David M. Sabatini
PMC | 2015
Kenjiro Kami; Laura M. Shelton; Shakti Ramkissoon; Keith L. Ligon; Matija Snuderl; Dohoon Kim; Brian Prescott Fiske; Kivanc Birsoy; Elizaveta Freinkman; Richard Possemato; Yakov Chudnovsky; Michael E. Pacold; Walter W. Chen; Jason R. Cantor; Dan Yi Gui; Manjae Kwon; Seong Woo Kang; Matthew G. Vander Heiden; David M. Sabatini
PMC | 2014
Elizaveta Freinkman; William C. Comb; Jason R. Cantor; Wai Leong Tam; Prathapan Thiru; Naama Kanarek; Brian Bierie; Yoav D. Shaul; Dohoon Kim; Michael E. Pacold; Walter W. Chen; Richard Possemato; Ferenc Reinhardt; Robert A. Weinberg; Michael B. Yaffe; David M. Sabatini
PMC | 2012
David M. Sabatini; Jason R. Cantor