Department of Internal Medicine
Cardiovascular Division
Research Opportunities
Joel Linden, MD
Targeting adenosine receptors for the treatment of tissue transplantation, sickle cell anemia, diabetes and cancer.
Receptors for the purine nucleoside adenosine have been found on all mammalian tissues. Activation of these receptors regulates cardiac and vascular functions. Recently we have been interested in investigating the effects of adenosine receptors on inflammatory cells. We have found that activation of A2A adenosine receptors is profoundly inhibitory to mast cells, neutrophils, platelets and macrophages. Activation of these receptors following ischemia can reduce damage that occurs in heart, lung and kidney during reperfusion following ischemia. Activation of another adenosine receptor subtype, A2B, has a pro-inflammatory effect to facilitate allergen and ischemia-induced mast cell degranulation which results in the release of histamine and other allergic mediators. Blockage of A2B receptors reduces allergic and inflammatory responses.
We are studying the effects of adenosine A2A receptor agonists to inhibit heart, liver and lung injury including lung injury cause by sickle cell anemia. Some of these effects are mediated by preventing the activation of NKT cells. We are studying the effects of adenosine A2B receptor antagonists to reverse insulin resistance in type II diabetes. These effects are mediated by inhibition cytokine production. We are studying adenosine A2A and A2B receptor antagonists for the treatment of cancer. These effects are mediated by T cell activation and inhibition of tumor angiogenesis.
