Costas A. Lyssiotis

Assistant Professor, Molecular and Integrative Physiology

Ph.D., Chemical Biology, The Scripps Research Institute
B.S., Chemistry and Biochemistry, University of Michigan - Ann Arbor

Research Focus: Tumor Metabolism, Cancer, Pancreatic Cancer, Autoimmunity

Phone: 734.615.9133
E-mail: clyssiot@med.umich.edu

The metabolic requirements and pathways engaged in growing cells, like cancer cells, are vastly different than those of a cell in a state of quiescence. Among these differences are the need for the basic cellular building blocks (e.g. carbohydrates, amino acids, fats). In a normal, healthy mammalian cell, nutrient uptake and biosynthesis processes are controlled by complex networks of extracellular signaling.

In cancer cells, these networks are hijacked (through gains in oncogenes and loss of tumor suppressors), which allow the cells to obtain nutrients and engage biosynthetic machinery in a cell autonomous manner. In fact, the cell autonomous control of nutrient uptake and metabolism is a principle requirement for the formation of a cancer cell, and metabolic pathways are rewired to support the needs of the tumor.

A consequence of deregulating nutrient uptake and rewiring metabolic pathways is that cancer cells become uniquely dependent on pathways and processes that normal cells can live without. Using a variety of biochemical and analytical techniques, the Lyssiotis lab maps how these processes are rewired and uses this knowledge to design targeted therapies. We are exploring the intersection between cell signaling and metabolism in a number of contexts leading to the description of new or differentially utilized pathways in various cancers and stem cells.




2015 Tri-Institutional Breakout Prize for Junior Investigators
2014-2016 Dale F. Frey Award for Breakthrough Scientists (Damon Runyon Cancer Research Foundation)
Pathway to Leadership Award (Pancreatic Cancer Action Network / American Association for Cancer Research)


Representative Publications

  1. Chakrabarti G, Moore Z, Luo X, Ilcheva M, Ali A, Anderson GG, Padanad M, Scaglioni PP, Cantley LC, Kimmelman AC, DeBerardinis RJ, *Lyssiotis CA, *Boothman DA [co-senior authors]. Targeting KRAS-reprogrammed Glutamine Metabolism Sensitizes Pancreatic Cancer to NQO1-bioactivatable Drugs. Cancer & Metabolism, In Press.

  2. Sadanandam A, Wullschleger S, Lyssiotis CA, Grötzinger C, Barbi S, Bersani S, Körner J, Wafy I, Mafficini A, Lawlor RT, Asara JM, Blaker H, Cantley LC, Wiedenmann B, Scarpa A, Hanahan D. A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Metastatic, Developmental, and Metabolic Characteristics. Cancer Discovery, In Press.

  3. Glick GD, Rossignol R, Lyssiotis CA, Wahl D, Lesch C, Sanchez B, Liu X, Hao LY, Taylor C, Hurd A, Ferrara JL, Tkachev V, Byersdorfer C, Boros L, Opipari AW. Targeting Increased Anaplerotic Metabolism of Pathogenic T cells to Treat Immune Disease. J Pharmacol Exp Ther 2014;351:298–307.

  4. Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sanchez N, Marchesini M, Carugo A, Green T, Seth S, Giuliani V, Kost-Alimova M, Muller F, Colla S, Nezi L, Genovese G, Deem AK, Kapoor A, Carugo A, Yao W, Brunetto E, Kang Y, Yuan M, Asara JM, Wang YA, Heffernan TP, Kimmelman AC, Wang H, Fleming J, Cantley LC, DePinho R, Draetta G. Oncogene Ablation-Resistant Pancreatic Cancer Cells Depend on Mitochondrial Function. Nature 2014;30:628–32.

  5. Yeo H, Lyssiotis CA, Zhang Y, Ying H, Asara JM, Cantley LC, Paik JH. FoxO3 Coordinates Metabolic Pathways to Maintain Redox Balance in Neural Stem Cells. EMBO J2013;32:2589–2602.

  6. *Son J, *Lyssiotis CA [*co-lead authors], Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Glutamine Supports Pancreatic Cancer Growth Through a KRAS-Regulated Metabolic Pathway. Nature 2013;496:101–105.

  7. Shyh-Chang N, Locasale JW, Lyssiotis CA, Zheng Y, Teo RY, Ratanasirintrawoot S, Zhang J, Onder T, Unternaehrer JJ, Zhu H, Asara JM, Daley GQ, Cantley LC. Influence of Threonine Metabolism on S-Adenosyl-Methionine and Histone Methylation. Science 2012;339:222–226.

  8. *Ying H, *Kimmelman AC, *Lyssiotis CA [*co-lead authors], Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik J, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA. Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism. Cell 2012;149:656–670.