Katherine Weilbaecher, MD
Year elected: 2008
Current membership category: Active
Washington University School of Medicine
Professor of Med and Cellular Biol & Physiol
660 South Euclid Avenue, Box 8069
St. Louis, MO 63110
United States of America
The laboratory of Katherine Weilbaecher studies the molecular pathogenesis of bone metastasis. The Weilbaecher laboratory has demonstrated that beta 3 integrins expressed on platelets and osteoclasts mediate metastatic progression, and that tumor induced dysregulation of platelet and osteoclast function may be a critical downstream mediator of bone metastasis. Her laboratory recently demonstrated that administration of platelet activation inhibitors, aspirin and the ADPase, APT102, abrogated bone metastases in animal models suggesting a role for the use of platelet inhibitors to prevent metastases. In addition to finding that osteoclast inhibition can interfere with bone metastases, her laboratory found that increased osteoclast activity can promote tumor growth in bone. Her laboratory found that a commonly used adjunct to cancer chemotherapy, G-CSF, stimulated osteoclast activity and bone loss in mice and that G-CSF treated mice had increased tumor burden in bone. Pharmacologic and genetic inhibition of osteoclast activity abrogated the tumor growth enhancing effects of G-CSF. Her laboratory also found that genetic disruption of hematopoeitic cell homing molecule, CXCR4, enhanced osteoclastogenesis and resulted in significant bone loss and suggest that CXCR4 is a negative regulator of osteoclast activity. Tumor growth specifically in bone was increased in mice reconstituted with CXCR4 null hematopoietic cells and this tumor growth enhancement phenotype was abrogated with the OC inhibitor, zoledronic acid. These data underscore the importance of evaluating the effects of cancer therapies on tumor microenvironment in bone, particularly in patients with bone metastases and provide ground-work for the development of targeted anti-metastasis therapies.
Washington University School of Medicine in St. Louis (Primary)
Deborah J. Veis, MD, PhD is the representative at this institution.