Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania
The past decade has seen a growing appreciation that cancers are not just clonal expansions of tumor cells but aberrant tissues, comprising many distinct cells types. From this has evolved the notion that effective cancer therapies should combine agents that target not only the tumor cells themselves but also the tumor microenvironment. The overarching goal of my laboratory is to understand how the tumor microenvironment is assembled and maintained, with particular focus on the generation and maintenance of the tumor blood supply – the process of tumor angiogenesis. Tumor angiogenesis is a dynamic process involving continuous elaboration and remodeling of blood vessels in the tumor microenvironment. It is driven by the precocious production of various angiogenic factors of which the best characterized is VEGF, an endothelial mitogen whose regulation and downstream effectors have been the focus of intense investigation for over a decade. However, angiogenesis is under constant restraint by a variety of endogenous inhibitors, and it has become clear that modulation of these inhibitors also plays a critical role in tumor angiogenesis but the mechanisms by which they do so are far less well understood.
The Ryeom Laboratory
The laboratory is particularly interested in understanding how angiogenesis inhibitors act to limit endothelial cell activation and angiogenesis, and how they might be used therapeutically to treat cancers. Specific projects include:
i) Understanding why Down syndrome individuals are protected against cancer and the role of the calcineurin inhibitor, DSCR1 in suppressing VEGF-mediated angiogenesis;
ii) Identifying new cell extrinsic tumor suppressor functions of p53 and p19ARF: regulation of the endogenous angiogenesis inhibitors thrombopsondin-1 and endostatin;
iii) Investigating a novel role for the endogenous angiogenesis inhibitor thrombospondin-1 in mediating oncogene-induced senescence;
iv) Immune surveillance and the role of the endogenous angiogenesis inhibitors thrombospondin-1 and endostatin in tumor immunity.