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Michael Lukey

Michael James Lukey

Assistant Professor
Cancer Center Member

Ph.D., University of Oxford, U.K., 2010

lukey@cshl.edu | 516-367-5016

Faculty Profile

Tumor growth depends upon cancer cells acquiring nutrients from their environment and using these molecules to fuel proliferation. My group studies the nature and regulation of metabolic adaptation during tumorigenesis and metastasis, with the intention of identifying metabolic vulnerabilities that can be targeted for cancer therapy.

Proliferative signals in mammalian cells drive biosynthetic programs that support cell growth and replication. In healthy cells this process is tightly regulated by growth factors, but in cancer cells oncogenic lesions can result in continuous signaling to the metabolic machinery. Oncogene-driven metabolic reprogramming supports tumorigenesis but renders cells sensitive to specific metabolic stresses, a phenomenon that is exploited for cancer therapy. Because the distribution of nutrients varies markedly between organs, cancer cells growing at different sites in the body – and in different regions of the tumor microenvironment—must employ a range of metabolic strategies to fuel their growth. We aim first to understand the nature and regulation of metabolic adaptations in the different stages of cancer, and then to develop therapeutic strategies that target resulting vulnerabilities. We are especially interested in the biochemical processes underlying nutrient sensing and metabolic/redox homeostasis, including regulation of the protein post-translational modification landscape by reactive metabolites. We are also exploring the reciprocal connections between tumor metabolism and host physiology, recognizing that metabolic therapies must be designed to synergize with, and not to antagonize, the anti-tumor immune response.

METAvivor Early Career Investigator Award Jan. 2020 – present
Breast Cancer Coalition of Rochester Research Award April 2017 – April 2018

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All Publications

Modular synthesis of functional libraries by accelerated SuFEx click chemistry

13 Mar 2024 | Chemical Science | 15(11):3879-3892
Homer, Joshua, Koelln, Rebecca, Barrow, Andrew, Gialelis, Timothy, Boiarska, Zlata, Steinohrt, Nikita, Lee, Erinna, Yang, Wen-Hsuan, Johnson, Robert, Chung, Taemoon, Habowski, Amber, Vishwakarma, Dharmendra, Bhunia, Debmalya, Avanzi, Charlotte, Moorhouse, Adam, Jackson, Mary, Tuveson, David, Lyons, Scott, Lukey, Michael, Fairlie, W, Haider, Shozeb, Steinmetz, Michel, Prota, Andrea, Moses, John

Metabolic partitioning in the brain and its hijacking by glioblastoma

30 Aug 2023 | Genes & Development | 37:681-702
de Ruiter Swain, Jed, Michalopoulou, Evdokia, Noch, Evan, Lukey, Michael, Van Aelst, Linda

Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia

11 Jul 2023 | Cell Metabolism | 35(7):1147-1162.e7
Ferrer, Miriam, Mourikis, Nicholas, Davidson, Emma, Kleeman, Sam, Zaccaria, Marta, Habel, Jill, Rubino, Rachel, Gao, Qing, Flint, Thomas, Young, Lisa, Connell, Claire, Lukey, Michael, Goncalves, Marcus, White, Eileen, Venkitaraman, Ashok, Janowitz, Tobias

Inhibition of mitochondrial metabolism by (-)-jerantinine A: synthesis and biological studies in triple-negative breast cancer cells

26 Apr 2023 | RSC Medicinal Chemistry | 14(4):710-714
Gialelis, Timothy, Wang, Zifei, Homer, Joshua, Yang, Wen-Hsuan, Chung, Taemoon, Hu, Qingting, Smedley, Christopher, Pawar, Nitin, Upadhyay, Nitinkumar, Tuveson, David, Lyons, Scott, Lukey, Michael, Moses, John

Ketogenic diet promotes tumor ferroptosis but induces relative corticosterone deficiency that accelerates cachexia

18 Feb 2023 | bioRxiv
Ferrer, Miriam, Mourikis, Nicholas, Davidson, Emma, Kleeman, Sam, Zaccaria, Marta, Habel, Jill, Rubino, Rachel, Flint, Thomas, Connell, Claire, Lukey, Michael, White, Eileen, Coll, Anthony, Venkitaraman, Ashok, Janowitz, Tobias

Early Neutrophilia Marked by Aerobic Glycolysis Sustains Host Metabolism and Delays Cancer Cachexia

1 Feb 2022 | Cancers | 14(4):963
Petruzzelli, M, Ferrer, M, Schuijs, M, Kleeman, S, Mourikis, N, Hall, Z, Perera, D, Raghunathan, S, Vacca, M, Gaude, E, Lukey, M, Jodrell, D, Frezza, C, Wagner, E, Venkitaraman, A, Halim, T, Janowitz, T

Enhancing the Efficacy of Glutamine Metabolism Inhibitors in Cancer Therapy

18 May 2021 | Trends in Cancer
Yang, Wen-Hsuan, Qiu, Yijian, Stamatatos, Olivia, Janowitz, Tobias, Lukey, Michael

Lysine succinylation and SIRT5 couple nutritional status to glutamine catabolism.

19 Mar 2020 | Molecular and Cellular Oncology | 7(3):1735284
Lukey, M, Greene, K, Cerione, R

SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis

16 Dec 2019 | Proceedings of the National Academy of Sciences of the United States of America
Greene, K, Lukey, M, Wang, X, Blank, B, Druso, J, Lin, M, Stalnecker, C, Zhang, C, Negron Abril, Y, Erickson, J, Wilson, K, Lin, H, Weiss, R, Cerione, R

Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer

1 Oct 2019 | Cell Reports | 29(1):76-88 e7
Lukey, M, Cluntun, A, Katt, W, Lin, M, Druso, J, Ramachandran, S, Erickson, J, Le, H, Wang, Z, Blank, B, Greene, K, Cerione, R

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