Barry Gumbiner PhD



, Seattle Children's Hospital , UW Medicine , University of Washington School of Medicine

Bio


Dr. Gumbiner and his team study how cadherin cell adhesion molecules and associated catenin proteins control tumor development and progression. Cadherins and catenins play important roles in the morphogenesis, maintenance, and regeneration of tissues, and alterations in their functions are important in cancer. One major effort of the laboratory is to understand how cadherins signal into the cell to control growth and differentiation through regulation of both the Wnt-beta-catenin pathway and the Hippo signaling pathway; the latter inhibits cell proliferation and participates in organ size control. Cadherins mediate contact inhibition of growth by stimulating the Hippo pathway, while growth factors, such as EGF, inhibit the Hippo pathway. They are investigating how these modes of regulation of the Hippo pathway affect the development of different types of tumors. Another major effort of the laboratory is to understand how cadherin adhesive function at the cell surface is regulated to control tissue architecture and tumor cell invasion. Loss of E-cadherin expression associated with the epithelial-mesenchymal transition (EMT) is known to promote tumorigenesis and metastasis. However, many tumors and metastases retain E-cadherin expression, and they have found that instead it can be inactivated at the cell surface to cause the loss in function. They have generated a novel class of monoclonal antibodies that activate E-cadherin at the cell surface to restore its adhesive function, and are evaluating whether they reduce tumor invasion and metastasis in animal models. He and his team are also studying how catenins and cancer-associated mutations in E-cadherin affect its ability to switch to the active state and regulate tumor development. The mechanisms by which cadherins and catenins affect tumor growth are varied and complex and offer potential approaches for intervention.

Institution


Seattle Children's Hospital Center for Developmental Biology and Regenerative Medicine Professor
University of Washington School of Medicine Pediatrics Professor