John A. Auchampach, PhD

Professor and Vice-Chair

Locations

Pharmacology and Toxicology

Contact Information

Biography

General Interests

Cardiovascular Pharmacology

Education

PhD, Pharmacology and Toxicology, Medical College of Wisconsin, 1992
BS, Pharmacy, South Dakota State University, 1988

Research Interests

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.

Structure activity relationship of 2-arylalkynyl-adenine derivatives as human A adenosine receptor antagonists.

(Yu J, Mannes P, Jung YH, Ciancetta A, Bitant A, Lieberman DI, Khaznadar S, Auchampach JA, Gao ZG, Jacobson KA.) Medchemcomm. 2018 Nov 01;9(11):1920-1932.
Repurposing of a Nucleoside Scaffold from Adenosine Receptor Agonists to Opioid Receptor Antagonists.

(Tosh DK, Ciancetta A, Mannes P, Warnick E, Janowsky A, Eshleman AJ, Gizewski E, Brust TF, Bohn LM, Auchampach JA, Gao ZG, Jacobson KA.) ACS Omega. 2018 Oct 31;3(10):12658-12678.
IL-13 promotes in vivo neonatal cardiomyocyte cell cycle activity and heart regeneration.

(Wodsedalek DJ, Paddock SJ, Wan TC, Auchampach JA, Kenarsary A, Tsaih SW, Flister MJ, O'Meara CC.) Am J Physiol Heart Circ Physiol. 2019 Jan 01;316(1):H24-H34.
Activation of adenosine A or A receptors causes hypothermia in mice.

(Carlin JL, Jain S, Duroux R, Suresh RR, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML.) Neuropharmacology. 2018 09 01;139:268-278.
Bitopic fluorescent antagonists of the A adenosine receptor based on pyrazolo[4,3-][1,2,4]triazolo[1,5-]pyrimidin-5-amine functionalized congeners.

(Duroux R, Ciancetta A, Mannes P, Yu J, Boyapati S, Gizewski E, Yous S, Ciruela F, Auchampach JA, Gao ZG, Jacobson KA.) Medchemcomm. 2017 Aug 01;8(8):1659-1667.
Species differences and mechanism of action of A adenosine receptor allosteric modulators.

(Du L, Gao ZG, Paoletta S, Wan TC, Gizewski ET, Barbour S, van Veldhoven JPD, IJzerman AP, Jacobson KA, Auchampach JA.) Purinergic Signal. 2018 03;14(1):59-71.
Bitopic fluorescent antagonists of the A2A adenosine receptor based on pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine functionalized congeners

(Duroux R, Ciancetta A, Mannes P, Yu J, Boyapati S, Gizewski E, Yous S, Ciruela F, Auchampach JA, Gao ZG, Jacobson KA.) Med Chem Commun. 2017 June 20;8: 1659-1667 .
Scaffold Repurposing of Nucleosides (Adenosine Receptor Agonists): Enhanced Activity at the Human Dopamine and Norepinephrine Sodium Symporters.

(Tosh DK, Janowsky A, Eshleman AJ, Warnick E, Gao ZG, Chen Z, Gizewski E, Auchampach JA, Salvemini D, Jacobson KA.) J Med Chem. 2017 04 13;60(7):3109-3123.
Lung injury pathways: Adenosine receptor 2B signaling limits development of ischemic bronchiolitis obliterans organizing pneumonia.

(Densmore JC, Schaid TR, Jeziorczak PM, Medhora M, Audi S, Nayak S, Auchampach J, Dwinell MR, Geurts AM, Jacobs ER.) Exp Lung Res. 2017 02;43(1):38-48.
Hypothermia in mouse is caused by adenosine A and A receptor agonists and AMP via three distinct mechanisms.

(Carlin JL, Jain S, Gizewski E, Wan TC, Tosh DK, Xiao C, Auchampach JA, Jacobson KA, Gavrilova O, Reitman ML.) Neuropharmacology. 2017 03 01;114:101-113.
Depletion of Tip60 from In Vivo Cardiomyocytes Increases Myocyte Density, Followed by Cardiac Dysfunction, Myocyte Fallout and Lethality.

(Fisher JB, Horst A, Wan T, Kim MS, Auchampach J, Lough J.) PLoS One. 2016;11(10):e0164855.
Purine (N)-Methanocarba Nucleoside Derivatives Lacking an Exocyclic Amine as Selective A3 Adenosine Receptor Agonists.

(Tosh DK, Ciancetta A, Warnick E, O'Connor R, Chen Z, Gizewski E, Crane S, Gao ZG, Auchampach JA, Salvemini D, Jacobson KA.) J Med Chem. 2016 Apr 14;59(7):3249-63.

John A. Auchampach, PhD