Joel M. Linden, PhD
Hypothalamic, pituitary and peripheral interactions in the pathogenesis of pituitary adenomas invasion and recurrence; molecular genetics characteristics of gliomas and tumor behavior
Angiogenesis: Adenosine is produced by hypoxic or proliferating tissue. It is a powerful stimulus for angiogenesis. Adenosine is mitogenic for endothelial cells via activation of A2B adenosine receptors which in turn stimulate the production of VEGF and VEGF receptors. A1 or A3 adenosine receptors on macrophages or mast cells also indirectly stimulate angiogenesis by stimulating the release of various vascular growth factors. In collaboration with Amy Tucker, M.D. in the department of internal medicine we are synthesizing new compounds that either block or allosterically regulation adenosine receptors to determine how they regulate angiogenesis. Such compounds might be used as adjunctive therapy to retard angiogenesis in tumors.
Immunotherapy: A2A and A2B adenosine receptors on lymphocytes and antigen presenting cells appear to inhibit T-cell function. When tumors are killed by the immune system adenosine is released in high quantities and may act to suppress immune cell function. In collaboration with Victor Engelhard, PhD in the Department of Microbiology, we are synthesizing new compounds that potently block A2A and A2B receptors. These are being evaluated to determine if they facility T-cell mediated killing of tumors.