Professor, Department of Medicine
Chief, Division of Endocrinology, Diabetes & Metabolism
University of Wisconsin
Co-Investigator: William J. Gradishar, MD FACP, Feinberg School of Medicine, Northwestern University
Basal-like tumors are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Cryns and colleagues have shown that a cell stress protein called αB-crystallin contributes to the aggressive behavior of basal-like tumors. More recently, they have developed new in vivo models of basal-like breast cancer that spread (“metastasize”) from the breast to the brain and other organs. Using these in vivo models, the researchers have demonstrated that αB-crystallin is a key regulator of breast cancer metastasis. In 2012-2013, they created a new genetic model of breast cancer and demonstrated that deleting the αB-crystallin gene inhibits lung metastasis. The team has also demonstrated that reducing the expression of αB-crystallin may make cancer cells more sensitive to chemotherapy and some targeted therapies. Finally, they have identified proteins that interact with αB-crystallin and are determining the potential role of these proteins in metastasis. These studies provide novel insights into the molecular mechanisms of basal-like breast cancer and point to αB-crystallin as a promising drug target in these poor-prognosis breast tumors.
Basal-like tumors are clinically aggressive and lack targeted therapies because they are estrogen receptor (ER)-negative and HER2-negative. Dr. Cryns and colleagues have shown that a cell stress protein called αB-crystallin contributes to the aggressive behavior of basal-like tumors. More recently, Dr. Cryns and his team have developed new in vivo models of basal-like breast cancer and shown that αB-crystallin regulates the spread (“metastasis”) of breast tumor cells to the brain and other organs. During the current year of BCRF funding, the researchers are investigating the mechanisms by which αB-crystallin promotes metastasis and screening for drugs to block the expression of this protein.
Dr. Cryns received his bachelor's degree summa cum laude in biochemistry from Harvard, his medical degree from Harvard Medical School, and he did specialty training in endocrinology at Massachusetts General Hospital. His laboratory focuses on mechanisms of cell death. His lab was the first to report that a protein called αB-crystallin protects breast cancer cells from chemotherapy killing and elucidated the mechanism of this protection. Recently, Dr. Cryns's lab demonstrated that αB-crystallin plays an important role in an aggressive type of breast cancer (basal-like tumors) and predicts poor clinical outcomes. His research has been published in top medical journals, including the New England Journal of Medicine and the Journal of Clinical Investigation. His work has also been featured on National Public Radio's All Things Considered and highlighted in Nature, and Nature Reviews Cancer.
Dr. Cryns's research is funded by the NIH, The Breast Cancer Research Foundation, the Susan G. Komen Breast Cancer Foundation and other agencies. He has also served on numerous study sections at NIH and other agencies. Dr. Cryns is currently on the editorial board of Molecular Endocrinology. He 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.