Costas A. Lyssiotis, PhD

Assistant Professor, Molecular & Integrative Physiology

6308 Cancer Center
1150 E. Medical Center Drive
Ann Arbor, MI 48109-5942

734-615-9133

Biography

Dr. Lyssiotis is an Assistant Professor at the University of Michigan Medical School with appointments in the Departments of Physiology and Medicine. His lab studies the biochemical pathways and metabolic requirements that enable tumor survival and growth and, in particular, how this information can be used to design targeted therapies. Among his many contributions, Dr. Lyssiotis demonstrated that pancreatic cancers are addicted to glucose and glutamine and use these nutrients in previously undescribed pathways to make DNA and to generate free radical-combating antioxidants, respectively. For this work, he has been awarded a Pathway to Leadership Grant from the Pancreatic Cancer Action Network, the Dale F. Frey Award for Breakthrough Scientists from the Damon Runyon Cancer Research Foundation and the Tri-Institutional Breakout Prize for Junior Investigators.

Areas of Interest

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, diseases and during development.

Selected Publications:

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.

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.

*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.

*Ying H, *Kimmelman AC, *LyssiotisCA [*co-lead authors], HuaS, Chu GC, Fletcher-Sananikone E, Locasale JW, SonJ, 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.

Honors & Awards

  • 2015-Tri-Institutional Breakout Prize for Junior Investigators
  • 2014-Dale F. Frey Award for Breakthrough Scientists (Damon Runyon Cancer Research Foundation)
  • 2013-Pathway to Leadership Award (Pancreatic Cancer Action Network / American Association for Cancer Research)

Credentials

  • PhD, Chemical Biology, The Scripps Research Institute
  • BS, Chemistry and Biochemistry, University of Michigan - Ann Arbor