John A. Auchampach, PhD

Professor and Vice-Chair

Locations

Pharmacology and Toxicology

Contact Information

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.

First Potent Macrocyclic A3 Adenosine Receptor Agonists Reveal G-Protein and β-Arrestin2 Signaling Preferences.

(Tosh DK, Fisher CL, Salmaso V, Wan TC, Campbell RG, Chen E, Gao ZG, Auchampach JA, Jacobson KA.) ACS Pharmacol Transl Sci. 2023 Sep 08;6(9):1288-1305 PMID: 37705595 PMCID: PMC10496144 09/14/2023
Species dependence of A3 adenosine receptor pharmacology and function.

(Gao ZG, Auchampach JA, Jacobson KA.) Purinergic Signal. 2023 Sep;19(3):523-550 PMID: 36538251 PMCID: PMC9763816 SCOPUS ID: 2-s2.0-85173914165 12/21/2022
Pharmacological inhibition of the acetyltransferase Tip60 mitigates myocardial infarction injury.

(Wang X, Wan TC, Kulik KR, Lauth A, Smith BC, Lough JW, Auchampach JA.) Dis Model Mech. 2023 May 01;16(5) PMID: 36341679 PMCID: PMC9672930 SCOPUS ID: 2-s2.0-85141362492 11/08/2022
First Potent Macrocyclic A3 Adenosine Receptor Agonists Reveal G-Protein and β-Arrestin2 Signaling Preferences

(Tosh DK, Fisher CL, Salmaso V, Wan TC, Campbell RG, Chen E, Gao ZG, Auchampach JA, Jacobson KA.) ACS Pharmacology and Translational Science. 8 September 2023;6(9):1288-1305 SCOPUS ID: 2-s2.0-85168520378 09/08/2023
Structure-Activity Studies of 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as A3 Adenosine Receptor Positive Allosteric Modulators.

(Fallot LB, Suresh RR, Fisher CL, Salmaso V, O'Connor RD, Kaufman N, Gao ZG, Auchampach JA, Jacobson KA.) J Med Chem. 2022 Nov 24;65(22):15238-15262 PMID: 36367749 PMCID: PMC10354740 SCOPUS ID: 2-s2.0-85141945462 11/12/2022
Characterization of Dual-Acting A3 Adenosine Receptor Positive Allosteric Modulators That Preferentially Enhance Adenosine-Induced Gαi3 and GαoA Isoprotein Activation.

(Fisher CL, Fallot LB, Wan TC, Keyes RF, Suresh RR, Rothwell AC, Gao ZG, McCorvy JD, Smith BC, Jacobson KA, Auchampach JA.) ACS Pharmacol Transl Sci. 2022 Aug 12;5(8):625-641 PMID: 35983277 PMCID: PMC9380209 08/20/2022
Measuring cardiomyocyte cell-cycle activity and proliferation in the age of heart regeneration.

(Auchampach J, Han L, Huang GN, Kühn B, Lough JW, O'Meara CC, Payumo AY, Rosenthal NA, Sucov HM, Yutzey KE, Patterson M.) Am J Physiol Heart Circ Physiol. 2022 Apr 01;322(4):H579-H596 PMID: 35179974 PMCID: PMC8934681 SCOPUS ID: 2-s2.0-85127729067 02/19/2022
Conditional depletion of the acetyltransferase Tip60 protects against the damaging effects of myocardial infarction.

(Wang X, Wan TC, Lauth A, Purdy AL, Kulik KR, Patterson M, Lough JW, Auchampach JA.) J Mol Cell Cardiol. 2022 Feb;163:9-19 PMID: 34610340 PMCID: PMC8816866 SCOPUS ID: 2-s2.0-85116932867 10/06/2021
A3 adenosine receptor agonists containing dopamine moieties for enhanced interspecies affinity.

(Tosh DK, Salmaso V, Campbell RG, Rao H, Bitant A, Pottie E, Stove CP, Liu N, Gavrilova O, Gao ZG, Auchampach JA, Jacobson KA.) Eur J Med Chem. 2022 Jan 15;228:113983 PMID: 34844790 PMCID: PMC8865922 SCOPUS ID: 2-s2.0-85120162519 12/01/2021
Evidence that the acetyltransferase Tip60 induces the DNA damage response and cell-cycle arrest in neonatal cardiomyocytes.

(Wang X, Lupton C, Lauth A, Wan TC, Foster P, Patterson M, Auchampach JA, Lough JW.) J Mol Cell Cardiol. 2021 Jun;155:88-98 PMID: 33609538 PMCID: PMC8154663 SCOPUS ID: 2-s2.0-85102458794 02/21/2021
Myh6-driven Cre recombinase activates the DNA damage response and the cell cycle in the myocardium in the absence of loxP sites.

(Wang X, Lauth A, Wan TC, Lough JW, Auchampach JA.) Dis Model Mech. 2020 Dec 18;13(12) PMID: 33106234 PMCID: PMC7758623 SCOPUS ID: 2-s2.0-85098138727 10/28/2020
Direct Comparison of (N)-Methanocarba and Ribose-Containing 2-Arylalkynyladenosine Derivatives as A3 Receptor Agonists.

(Tosh DK, Salmaso V, Rao H, Campbell R, Bitant A, Gao ZG, Auchampach JA, Jacobson KA.) ACS Med Chem Lett. 2020 Oct 08;11(10):1935-1941 PMID: 33062176 PMCID: PMC7549272 10/17/2020