Vincent L. Cryns, MD
Professor, Department of Medicine
Marian A. and Rodney P. Burgenske Chair,
Endocrinology, Diabetes & Metabolism
University of Wisconsin
Improving outcomes in breast cancer by identifying aberrant cell processes that lead to tumor formation and progression.
Basal-like triple-negative breast cancers are aggressive and lack targeted therapies because they don’t depend on the estrogen or progesterone hormones or HER2 for growth, hence the term “triple-negative.” Drs. Cryns and Gradishar are studying a cell stress protein called αβ-crystallin, which contributes to the aggressive behavior of basal-like/triple-negative breast cancer (TNBC) by interacting with cancer-promoting proteins. They have shown that it interacts with a mutant form of p53, the most commonly mutated gene in cancer, and links p53 to Akt, a growth-promoting protein that is often upregulated in cancer. Their work may lead to the identification of new approaches to target oncogenes in a broad spectrum of breast tumors.
The team has discovered that mutant p53 depends on αβ-crystallin to promote tumor formation. In addition, they identified a promising drug that reduces αβ-crystallin levels in breast cancer cells, and they plan to test this drug and related ones in TNBC models. Their findings could lead to completely new strategies to target and treat aggressive TNBC.
In the coming year, Drs. Cryns and Gradishar aim to delineate the effects of inhibiting αβ-crystallin on the stability of mutant p53 and on the activation of Akt. They hypothesize that without αβ-crystallin, mutant p53 will not be able to function, Akt will not be activated and be able to promote tumor growth, and breast cancer cells will die. The team will also determine whether inhibiting αβ-crystallin affects oncogenic transformation and tumor progression that is mediated by mutant p53.
Vincent Cryns, MD, is the Marian A. and Rodney P. Burgenske Chair in Diabetes Research and Chief, Division of Endocrinology, Diabetes & Metabolism at the University of Wisconsin School of Medicine and Public Health. He received his bachelor’s and medical degrees from Harvard and did subspecialty training in endocrinology at Massachusetts General Hospital. Before coming to Madison, Dr. Cryns was a Professor of Medicine at Northwestern University’s Feinberg School of Medicine.
Dr. Cryns leads a multidisciplinary team who focus on understanding how cells die. His group is especially interested in elucidating how abnormalities in cell death contribute to diseases such as cancer and obesity and in translating these insights into improved therapies. Dr. Cryns’ research is funded by the NIH, the Breast Cancer Research Foundation and other agencies. His work has been featured on National Public Radio’s "All Things Considered" and highlighted in Nature and Nature Reviews Cancer. Dr. Cryns has been the recipient of several awards, including an Outstanding Junior Faculty Award from the Avon Foundation, and he is an elected member of the American Society for Clinical Investigation.
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