Phillip G. Kopf, PhD

Associate Professor


Phillip G. Kopf, Ph.D.

Department of Pharmacology
Chicago College of Osteopathic Medicine
Midwestern University

Office: Science Hall 322-I
Phone: 630-515-6427
Fax: 630-515-6295
E-mail: pkopf@midwestern.edu

 

 

 

EDUCATION

Postdoc Medical College of Wisconsin 2009-2012
PhD Biomedical Sciences Universtiy of New Mexico 2008
BS Biology Truman State University 2001

RESEARCH INTERESTS

Elevated circulating aldosterone levels are associated with hypertension, thrombosis formation, cardiac hypertrophy, and congestive heart failure. Aldosterone secretion is regulated by angiotensin II (Ang II), potassium, and adrenocorticotropic hormone (ACTH).  I am interested in the underlying mechanisms of aldosterone secretion with the goal to address the development and progression of hyperaldosteronism.  I currently have two research projects in this area that examine aldosterone secretion with two distinctive approaches: a pharmacological approach and a toxicological approach.

The role of 12-lipoxygenase in aldosterone secretion
Ang II stimulation of aldosterone secretion is mediated by AT1 receptors and phospholipase C-calcium downstream signaling.  Evidence exists for an essential role of the 12-lipoxygenase (12-LO) pathway in Ang II-stimulated aldosterone secretion.  However, the identity of 12-LO metabolites, as well as the mechanism and extent by which these metabolites contribute to Ang II-stimulation of aldosterone secretion remains unknown.  The goal of our studies is to understand the role of 12-LO in the regulation of aldosterone secretion.  Our current data indicates that endogenous production of 12-LO metabolites are produced by adrenal zona glomerulosa (ZG) cells and that a novel stereoselective G protein-coupled receptor (GPCR) is present on ZG cell plasma membranes.  Identification of the 12-LO metabolites and the receptor that mediates aldosterone secretion would provide a novel pharmacological target for the remediation of circulating aldosterone levels.

Polybrominated diphenyl ethers (PBDEs) and steroidogenesis
PBDEs are widely used flame retardants.  PBDEs leach into the environment, bioaccumulate, and are detected in U.S. breast milk samples.  Some of these PBDEs upregulate enzymes involved in steroidogenesis in a human adrenocortical cell line.  With growing evidence supporting a role for environmental pollutants in the development of cardiovascular disease, an investigation into the potential role of these PBDEs in the alteration of aldosterone synthesis is warranted.  Our current data suggest that PBDEs induce aldosterone secretion from cultured ZG cells in a concentration-dependent manner. Future studies will further characterize this response and determine if chronic PBDE exposure results in hyperaldosteronism.

SELECTED PUBLICATIONS (see PubMed Results)

Kopf PG, Park SK, Herrnreiter A, Krause C, Roques BP and Campbell WB.  2017.  Obligatory Metabolism of Angiotensin II to Angiotensin III for Zona Glomerulosa Cell-Mediated Relaxations of Bovine Adrenal Cortical Arteries.  Endocrinology.

Asurudeen I, Kopf PG, Gauthier KM, Bornstein SR, Cowley AW, and Campbell WB.  2014.  Aldosterone Secretagogues Increase Adrenal Blood Flow in Male Rats.  Endocrinology.  155:127-132.

Kopf PG and Campbell WB.  2013.  Endothelial Metabolism of Angiotensin II to Angiontensin III, not Angiotensin (1-7), Augments the Vasorelaxation Response in Adrenal Cortical Arteries.  Endocrinology.  154:4768-4776.

Oki K, Kopf PG, Campbell WB, Luis Lam M, Yamazaki T, Gomez-Sanchez CE, and Gomez-Sanchez EP.  2013.  Angiotensin II and III Metabolism and Effects on Steroid Production in the HAC15 Human Adrenocortical Cell Line.  Endocrinology. 154:214-221.

Kopf PG, Gauthier KM, Zhang DX, Falck JR, and Campbell WB.  2011.  Angiotensin II Regulates Adrenal Vascular Tone Through Zona Glomerulosa Cell-Derived EETs and DHETs.  Hypertension. 57:323-329.

Kopf PG, Scott JA, Agbor LN, Boberg J, Elased KM, Huwe JK, and Walker MK.  2010.  Cytochrome P4501A1 is Required for Vascular Dysfunction and Hypertension Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin. Toxicol Sci. 117:537-546.

Kopf PG, Walker MK.  2010.  2,3,7,8-Tetrachlorodibenzo-p-Dioxin Increases Reactive Oxygen Species Production in Human Endothelial Cells Via Induction of Cytochrome P4501A1.  Toxicol Appl Pharmacol. 245:91-99.

Kopf PG, Zhang DX, Gauthier KM, Nithipatikom K, Yi XY, Falck JR, and Campbell WB.  2010.  Adrenic Acid Metabolites as Endogenous Endothelium- and Zona Glomerulosa-Derived Hyperpolarizing Factors.  Hypertension. 55:547-554.

Kopf PG and Walker MK.  2010.  Mechanisms of Xenobiotic-Induced Cardiovascular Toxicology: Halogenated Aromatic Hydrocarbons and Cardiovascular Disease.  Comprehensive Toxicology.  Second Ed.  Elsevier Limited, Oxford.

Kopf PG and Walker MK.  2009. Overview of Dioxin-Like Compounds, PCB, and Pesticide Exposures Associated with Developmental Heart Effects in Mammals, Fish, and Birds.  J Env Sci Health, Part C. 27:276-285.

Kopf PG, Huwe JK, and Walker MK.  2008.  Subchronic 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice.  Cardiovasc Toxicol. 8:181-193.

Aragon AC, Kopf PG, Campen MJ, Huwe JK, and Walker MK.  2008.  In Utero and Lactational 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure: Effects of Fetal and Adult Cardiac Gene Expression and Adult Cardiac and Renal Morphology.  Toxicol Sci. 101:321-330.