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Vincent L. Cryns, MD
Professor, Department of Medicine
Marian A. and Rodney P. Burgenske Chair,
Endocrinology, Diabetes & Metabolism
University of Wisconsin
Goal: To improve outcomes in breast cancer by identifying aberrant cell processes that lead to tumor formation and progression.
Impact: Drs. Cryns and Gradishar are studying a cell stress protein called alphaβ-crystallin—which contributes to the aggressive behavior of basal-like/triple-negative breast cancer (TNBC). They have shown that it interacts with a mutant form of p53, the most commonly mutated gene in cancer. Their work may lead to the identification of new approaches to target mutant p53 in a broad spectrum of breast tumors.
What’s next: The team will continue to screen libraries of chemical compounds to identify drugs that block the interaction between alphaB-crystallin and p53 and test them in laboratory studies.
Basal-like tumors, which include those classified as triple negative, are aggressive and lack targeted therapies. Drs. Cryns and Gradishar have shown that a protein called alphaβ-crystallin contributes to the aggressive behavior of these tumors and regulates the spread of breast cancer to organs such as the brain. Recently, they discovered that alphaB-crystallin binds to mutant p53 (the most commonly mutated gene in cancer) and keeps it active, promoting tumor growth. The team will now test drugs that block the interaction between alphaB-crystallin and p53, which may benefit those with triple negative and other forms of breast cancer
Full Research Summary
Research goal: Developing new approaches to treat aggressive breast cancers.
Impact: 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, thus the term “triple-negative”. Drs. Cryns and Gradishar are investigating a cell stress protein called alphaβ-crystallin that contributes to the aggressive behavior of basal-like/triple-negative breast cancer (TNBC). Their findings may inform new targeted therapies that would prevent this protein from promoting metastasis.
Current investigation: The team is screening libraries of chemical compounds to identify drugs that block the interaction between alphaβ-crystallin and p53, the most commonly mutated gene in cancer. Alphaβ-crystallin binds directly to mutant p53 and keeps it active, thereby promoting tumor growth. Drugs that block the interaction between alphaB-crystallin and p53 are predicted to cause tumor cell death.
What they’ve learned so far: Drs. Cryns and Gradishar showed that alphaβ-crystallin promotes survival of breast cancer stem cells—specialized cells that are suspected to drive metastasis— by increasing expression of a molecule called IL-6 that is involved in inflammatory response. This suggests that it may be a target for stopping metastasis.
What’s next: During the next year, the team will test promising drugs in laboratory models of breast cancer, including miniature tumors grown in a dish.
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.