Research in the McDonald lab studies mechanisms and consequences of blood vessel changes in cancer and inflammation to determine the contributions of altered vascular growth and function to disease pathophysiology and treatment. In-vivo cell biological approaches have been developed for use in mouse models to learn how the vasculature remodels during disease progression and how these alterations can serve as therapeutic targets.
Ongoing experiments are examining the processes underlying defective endothelial barrier function in inflammation. New strategies are being explored to reverse vascular leakage by regulating signaling pathways that control the junctions between endothelial cells. Here the focus is the regulation of endothelial tight junctions and adherens junctions by angiopoietins, Tie1 and Tie2 tyrosine kinase receptors, and endothelial cell-specific phosphotyrosine phosphatases.
Other work is elucidating the antitumor actions of engineered oncolytic vaccinia viruses that home selectively to tumor blood vessels and reduce tumor growth. Viral infection of tumor blood vessels is followed by focal tumor infection accompanied by widespread tumor cell killing mediated by a robust immune response. Studies are examining immune checkpoint inhibitor amplification of the action of genetically modified vaccinia viruses on primary tumors and on metastases. The overall goal is to advance the mechanistic understanding of blood vessel growth and remodeling and to develop strategies that exploit changes in vascular phenotype in the treatment of cancer and inflammatory diseases.