John A. Auchampach, PhD
(414) 456-5643 | Fax: (414) 456-6545
BS - Pharmacy, South Dakota State University - 1988
PhD - Pharmacology and Toxicology, Medical College of Wisconsin - 1992
Adenosine production by cells is increased when cellular energy utilization and the breakdown of adenosine tri-phosphate (ATP) is increased. Thus, adenosine levels are elevated in tissues when there is not enough oxygen in the cells or during other pathological processes involving cellular stress, inflammation, and tissue injury. Through interaction with four related receptors termed A1, A2A, A2B, and A3 adenosine receptors - proteins found on the surface of cells that recognize adenosine and related ligands - adenosine affects many different disease processes, ranging from ischemic heart disease to cancer.
We are investigating the biological function of the two least understood adenosine receptor subtypes, the A2B and A3 adenosine receptors. In particular, the team is investigating how the A3 adenosine receptor modulates activity of certain immune cells and helps to protect the heart from ischemia/reperfusion injury, known commonly as a heart attack. As part of this project, new ligands for the A3 adenosine receptor are being developed, including novel allosteric modulator compounds that enhance the ability of the receptor to be activated by binding to a region that is distinctly different than the binding site for adenosine. In a second project, we are investigating the novel hypothesis that the A2B adenosine receptor contributes to stiffening of the heart during certain chronic cardiovascular diseases that lead to heart failure by promoting the formation of excess connective tissue, a pathological process termed cardiac fibrosis. A basic understanding of the function of each of the adenosine receptors is anticipated to identify new approaches for the treatment of a wide range of diseases.