Phone: (706) 721-1901

Fax: (706) 721-9799

Email: jdimig@mcg.edu

Office: CB-3210A / Lab: CB-3301

Current Projects | Grant Support as Principal Investigator | Lab | Honors & Awards | Invited Speaker | Selected Publications

One out of every four adults in the United States has hypertension and is at increased risk for the development of coronary artery disease, stroke, congestive heart failure, and end stage renal disease (ESRD). Although great strides have been made in providing more effective treatments of hypertension, kidney damage still progresses slowly during high blood pressure and the incidence of ESRD associated with hypertension is escalating. Another disease that is influenced by hypertension is stroke and this acute ischemic stroke is the third leading cause of death in the United States. The long-term objective of this project is the elucidation of mechanisms by which CYP450 metabolites influence kidney and cerebral vascular function in hypertension. We hypothesize that inhibition of epoxide hydrolase will increase CYP450 epoxide levels, lower blood pressure and prevent renal and cerebral vascular injury in hypertensive animals. The proposed studies are employing newly developed highly selective epoxide hydrolase inhibitors to determine their ability to lower arterial blood pressure and improve renal vascular function and decrease stroke induced brain damage in hypertension.

Obesity contributes significantly to the development of certain diseases like diabetes and hypertension. Obesity is the central phenotype in metabolic syndrome that clusters with other cardiovascular risk factors. These other risk factors include hypertension, type 2 diabetes, insulin resistance, low HDL cholesterol, elevated triglycerides, microalbuminuria, and atherosclerosis. A major cause of morbidity and mortality is the progression of end organ damage in obesity, diabetes and hypertension. Hypertension and obesity are both associated with a complex systemic inflammatory state that has been implicated in common medically important complications including endothelial dysfunction and insulin resistance. Likewise, endothelial dysfunction, inflammation and insulin resistance contribute to the glomerular damage in obese patients. Altered CYP450 epoxide metabolite production could be a major contributing factor to the endothelial dysfunction and inflammation associated with hypertension and obesity. This project will focus on the contribution of CYP450 epoxide metabolites to renal vascular damage in metabolic syndrome.

The long-term objective of this research project is to test the general hypothesis that CYP450 controlled generation of specific eicosanoids provides important mediators of vascular function. We have established that CYP450 epoxygenase metabolites produced by the endothelium have anti-hypertensive properties and proposed that the epoxides 11,12-EET and 14,15-EET are endothelium-derived hyperpolarizing factors (EDHFs). On the other hand, the CYP450 hydroxylase metabolite, 20-HETE, is produced by renal vascular smooth muscle cells, causes vascular constriction and has been implicated as a pro-hypertensive factor. Identification of the cell signaling pathways involved in the response to CYP450 metabolites and their role in hormonal and paracrine regulation of the vasculature remains unresolved. This project will integrate current knowledge of the functional significance of the vascular CYP450 pathway with advances in biomolecular approaches to describe the mechanism of action of 11,12-EET and 14,15-EET and 20-HETE and the physiological and/or pathophysiological importance of this pathway.

A contributing factor to hypertension and the resulting end-organ damage is an impaired endothelium. There is convincing evidence that endothelial dysfunction is linked to end organ damage in human essential and salt-sensitive hypertension. Vascular CYP450 epoxide production increases in response to high dietary salt and is inappropriately low during the development of salt-sensitive hypertension. As previously mentioned, 11,12-EET and 14,15-EET are EDHFs and have anti-hypertensive properties. Additionally, 11,12-EET has anti-inflammatory properties that could protect the vasculature and glomerulus during cardiovascular disease states. Cytokine suppression of CYP450 epoxygenase enzymes is a mechanism that could account for decreased 11,12-EET and 14,15-EET production and organ damage associated with salt-sensitive hypertension. This project focuses on the specific contribution of inappropriate epoxide regulation to endothelial dysfunction and glomerular injury in salt-sensitive hypertension. As a whole, this project will provide novel information on the interaction between cytokines and CYP450 epoxide levels in the long-term regulation of blood pressure and vascular and glomerular function during salt-sensitive hypertension.

Principal Investigator: National Institutes of Health, HLB Institute, R01 (HL59699), Oxygenase Metabolites and Renal Microvascular Reactivity

Principal Investigator: American Heart Association - Established Investigator Award (AHA 0440015N), Epoxide Hydrolase and Epoxygenase Metabolites as Renal & Cardiovascular Therapeutic Targets

Principal Investigator: National Institutes of Health, Phase I STTR (NS053002), Novel Epoxide Hydrolase Inhibitor for Stroke Prevention

Project Leader: National Institutes of Health, Program Project Grant (HL074167), Cytokines and Angiotensin II-Induced Hypertension. P.I. R.C. Webb, Project Title: Renal Endothelial Dysfunction in Salt-Sensitive Hypertension

Project Leader: National Institutes of Health - NIDDK Institute, Program Project Grant (DK38226), Role of Eicosanoids in Renal Function. PI: J.H. Capdevila, Project Title: Eicosanoids and Renal Microvascular Function

Sponsor: American Heart Association Postdoctoral Fellowship, Dr. Ahmed A. Elmarakby, Role of the Inflammatory Cytokine, TNFa in Angiotensin II Hypertension

Sponsor : American Heart Association Postdoctoral Fellowship, Dr. Jeffrey J. Olearczyk, Epoxides and the Prevention of Nephropathy Associated with Type 2 Diabetes and Hypertension

Sponsor : National Institutes of Health Predoctoral Fellowship, Alexis Simpkins, Vascular Protection by Epoxide Hydrolase Inhibition in Cerebral Ischemia

• 1992 Merck Sharp & Dohme Travel Fellowship Award, 46th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research.
• 1992-1995 NIH Postdoctoral Fellowship, National Research Service Award.
• 1998 Outstanding Faculty Award, Department of Physiology, Tulane University.
• 2000 Young Faculty Research Award, Southern Section: Am. Fed. for Medical Research.
• 2000 Fellow American Heart Association Council for High Blood Pressure Research.
• 2001 American Society of Hypertension/ Monarch Pharmaceuticals Young Scholars Award.
• 2004 Medical College of Georgia School of Medicine Outstanding Young Basic Science Faculty Award.
• 2004 AstraZeneca Young Investigator Award, Am. Physiological Society Renal Section.
• 2004-2008 American Heart Association Established Investigator

2005-2006

Winter Eicosanoid Conference, EETs and Soluble Epoxide Hydrolase Session, Baltimore, MD

16th Scientific Meeting of the Interamerican Society of Hypertension, Hypertension and Renal Damage Session, Cancun, Mexico

International Society of Nephrology Meeting, Endothelial Cell Biology and Renal Disease: from bench to prevention, New Jersey

Pfizer Global Research & Development, St. Louis, MO

University of Louisville
Ph.D. Physiology and Biophysics, 1990

Blackburn College
B.S. Biology, 1985

1990-1993 Postdoctoral Fellow, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI.

1993-1995 Research Instructor, Department of Physiology, Tulane University School of Medicine, New Orleans, LA.

1995-1998 Research Assistant Professor, Department of Physiology, Tulane University School of Medicine, New Orleans, LA.

1998-2001 Assistant Professor, Department of Physiology, Tulane University School of Medicine, New Orleans, LA.

2001-2006 Associate Professor, Vascular Biology Center & Department of Physiology, Medical College of Georgia, Augusta, GA.

2006 Professor,
Vascular Biology Center & Department of Physiology, Medical College of Georgia, Augusta, GA

• American Physiological Society
• Microcirculatory Society
• American Heart Association
• American Society of Hypertension
• American Society of Nephrology
• American Society of Pharmacology & Experimental Therapeutics
• American Association for the Advancement of Science