University of Wisconsin
Professor, Department of Medicine
Marian A. and Rodney P. Burgenske Chair,
Endocrinology, Diabetes & Metabolism
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 do not depend on the estrogen or progesterone hormones or HER2 for growth, hence the term “triple-negative.” Drs. Cryns and Gradishar are studying cell stress proteins called αβ-crystallin and Hsp27, which interact with cancer-promoting proteins and contribute to the aggressive behavior of basal-like/triple-negative breast cancer (TNBC) by. They have shown that αβ-crystallin and Hsp27 interact with a mutant form of p53, the most commonly mutated gene in cancer, and link 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 and Hsp27 to promote tumor formation. Over the past year, they have identified the mechanisms by which p53 and Akt are regulated by these proteins and how the p53 and Akt cancer pathways are linked. The team also discovered that αβ-crystallin and Hsp27 each directly bind and regulate other key cancer drivers to promote tumor growth. Finally, Drs. Cryns and Gradishar determined that blocking αβ-crystallin and Hsp27 triggers tumor cells to die. These findings could lead to fundamentally new treatment approaches for TNBC.
In the coming year, Drs. Cryns and Gradishar will use genetic approaches to block αβ-crystallin and Hsp27 and examine how this affects the activity and function of multiple cancer drivers including p53, Akt, and others—especially their ability to promote tumor growth and chemotherapy resistance. They will also examine whether other cell stress proteins play a similar role in tumor-promoting pathways.
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 completed 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 that focuses 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.
The Housewares Charity Foundation Award
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