Katherine Weilbaecher

Oliver M Langenberg Distinguished Professor of Science and Practice of Medicine, Professor of Pathology and Immunology, Professor of Cell Biology and Physiology

    • Source: Scopus
    1985 …2020

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    Research interests

    The laboratory of Dr. Katherine Weilbaecher studies the molecular pathogenesis of bone metastasis. The 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. The lab 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, the lab found that increased osteoclast activity can promote tumor growth in bone. They also 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. The lab 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.

    Areas of Clinical Interest

    Breast cancer, bone metastases, melanoma

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