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jlinden.jpgJoel Linden, Ph.D. and his team are focused on the study of adenosine receptors-proteins on the surface of cells that recognize adenosine and related compounds.  Adenosine production by cells is increased when cellular energy utilization and the breakdown of adenosine tri-phosphate (ATP) is increased.  Hence, adenosine levels are raised when a cell is stressed, activated, or when there is not enough oxygen in the cells, such is the case in ischemic heart disease and sickle cell disease.  

Linden is interested in adenosine's affect on disease processes.  He found that the adenosine receptor is a very powerful negative regulator of many cells of the immune system including, neutrophils, macrophages and T cells.  This is important to disease because by activating adenosine receptors, inflammatory processes can be inhibited.  Inflammation has been recognized to play an important role in many diseases, and this discovery opens up numerous new potential treatments for heart failure, diabetes, Crohn's disease, and sickle cell disease-many of which are associated with a low-grade, chronic inflammatory responses.

Linden found that many of the anti-inflammatory effects of adenosine are actually due to their effects on natural killer t-cells (NKT), which regulate a variety of immune responses, including the immune response to  tumors and certain infectious agents. For example, NKT cells are involved in ischemia reperfusion injury, which is a type of inflammation and tissue damage that occurs when you either transplant a tissue, have a heart attack, or in the presence of microvascular ischemic episodes which are common in sickle cell disease.  The damage caused by the immune system response in these cases is inhibited by adenosine. Tumors evade immune surveillance in part by generating large amouts of adenosine.  This suggests that adenosine receptor blockers can be used to enhance the effectiveness of tumor vaccines.

"We think that activating adenosine receptors has great potential to inhibit a wide-range of inflammatory and chronic diseases including arthritis, heart failure, atherosclerosis, type 2 diabetes and sickle cell anemia," said Linden.  "A person suffering from sickle cell anemia can go into sudden stress-induced crisis, which causes severe pain.  Our research shows that adenosine can be used to block these painful and destructive disease flare-ups. This is a new approach."