The Cryns Lab: Targeting Metabolic Stress in Cancer

Vincent Cryns, MD

Chief, Division of Endocrinology, Diabetes and Metabolism

Marian A. and Rodney P. Burgenske Chair

Phone: 608-262-4786

E-mail: vlcryns@medicine.wisc.edu

Faculty Bio Page

Education

◦         AB summa cum laude Harvard College, 1983

◦         MD Harvard Medical School, 1987

Selected Honors & Awards

◦         2012 Chair, Clinical Endocrinology Subcommittee, American Association for Cancer Research (AACR) Program Committee

◦         2010- Associate Editor-in-Chief, American Journal of Cancer Research

◦         Elected Member, American Society for Clinical Investigation (ASCI)

◦         Research featured in Nature, Nature Reviews Cancer, and National Public Radio

Research

The Cryns lab focuses on understanding how tumors adapt to and survive metabolic stress caused by their rapid growth. These metabolic adaptions are unique to cancer cells and represent promising drug targets to selectively eradicate tumors. We are particularly interested in translating these insights into improved cancer biomarkers and therapies.

Specific projects include:

Regulation of metastasis by the cell stress protein αB-crystallin. We have identified αB-crystallin as a novel mediator of lung and brain metastasis in breast cancer that inhibits stress-induced apoptosis and promotes multiple steps in the metastatic cascade. We are actively investigating the mechanisms by which αB-crystallin promotes metastasis and developing strategies to therapeutically target this conserved stress response protein.

Metabolic priming tumors to targeted therapies. We have developed a new therapeutic paradigm that uses a diet deficient in the amino acid methionine to metabolically prime tumor cells to die by increasing tumor expression of a cell death receptor (TRAIL-R2). Methionine restriction also reduces fat and improves metabolic health in mice. We are currently exploring the mechanisms underlying these effects and translating these observations into clinical trials in breast cancer.

 

Selected Recent Publications:

Malin D, Strekalova E, Petrovic V, Deal AM, Al Ahmad A, Adamo B, Miller CR, Ugolkov A, LivasyC, FritchieK, HamiltonE, Blackwell K, Geradts J, Ewend M, Carey L, Shusta EV, Anders CK, Cryns VL. αB-crystallin: a novel regulator of breast cancer metastasis to the brain. Clin Cancer Res 2014 20:56-67 (featured on above journal cover).

Malin D, Strekalova E, Petrovic V, Rajanala H, Sharma B, Ugolkov A, Gradishar WJ, Cryns VL. ERK-regulated αB-crystallin induction by matrix detachment inhibits anoikis and promotes lung metastasis in vivo. Oncogene 2015 34:5626-34.

Strekalova E, Malin D, Good DM,  Cryns VL. Methionine deprivation induces a targetable vulnerability in triple-negative breast cancer cells by enhancing TRAIL receptor-2 expression. Clin Cancer Res 2015 21: 2780-91.

Halo TL, McMahon KM, Angeloni NL, Xu Y, Wang W, Chinen AB, Malin D, Strekalova E, Cryns VL, Cheng C, Mirkin CA, Thaxton CS. NanoFlares for the detection, isolation, and culture of live tumor cells from human blood. Proc Natl Acad Sci USA 2014 111:17104-9.

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