Conklin Laboratory

The Conklin Lab investigates how environmental and tobacco product-derived pollutants alter cardiovascular health and disease risk.

Research

Keywords

Environmental cardiology, obesity, diabetes, tobacco, animal models of human disease, air pollution, cardiovascular toxicology, aldehyde metabolism.

Summary

Recent epidemiological studies reveal that cardiovascular disease and diabetes are antagonized by environmental pollutant exposure. The presence of aldehydes in complex air borne mixtures of particulate matter and gases (e.g., smog, tobacco smoke, automobile exhaust, etc) is well-documented but the contribution these aldehydes make to the cause of or exacerbation of cardiovascular diseases and diabetes is unknown. Additional sources of environmental aldehydes include foods and beverages. Moreover, environmental aldehydes can promote the formation of endogenous aldehydes via oxidative stress and lipid peroxidation, as well as by stimulating inflammatory processes. Aldehydes such as the toxic acrolein, can be formed from the metabolism of exogenous and endogenous compounds, such as allylamine, cyclophosphamide, and polyamines, within cardiovascular and systemic tissues to induce injury. We have focused on acrolein action in cardiovascular tissues over the past 10 years, and our studies show that acrolein is a powerful cardiovascular toxin that can induce dyslipidemia, injure the heart and blood vessels, and enhance thrombus formation (blood clotting). Future studies will focus on uncovering the mechanisms by which aldehydes such as acrolein promote cardiovascular toxicity to better understand how to intervene and to promote regulatory guidelines that protect public health.

Because metabolism of aldehydes, such as acrolein, is a likely an important determinant of acrolein tissue level, activity and detoxification, we have probed the role of aldehyde metabolizing enzymes as a way to understand the nature of aldehyde-induced cardiovascular toxicity. Recent studies demonstrate that tissue deficiency of the acrolein-metabolizing enzyme, glutathione-S-transferase (GST) P (Pi), affects the sensitivity of the cardiovascular tissues and extra-cardiac structures, including urinary bladder and liver. These data could help explain how GST polymorphisms, which are present in human populations, increase the relative risk for cardiovascular disease and diabetes in those individuals exposed to high levels of air pollution. Collectively, human epidemiological studies and our experimental models serve as notice of the potentially dramatic cardiovascular responses elicited by aldehyde exposure, especially in tissues with altered levels of aldehyde metabolizing enzymes, such as GSTs. Subsequent studies will focus on how GST deficiency increases cardiovascular sensitivity to air pollution and aldehydes.

Related Research Centers

Diabetes and Obesity Center - Animal Models and Phenotyping

ATRAC2.0 - Tobacco Addiction Center 

Lab Members

Animal Core Services

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Positions and Education

Biography

In 2003 Dr. Conklin joined the University of Louisville to conduct Environmental Cardiology research with Drs. Aruni Bhatnagar, Ph.D. and Sanjay Srivastava, Ph.D. He currently is supported by the NIH in the Diabetes and Obesity Center (COBRE DOC), an EPA-funded Superfund Research Center, and an FDA-funded Tobacco Center of Regulatory Science with the American Heart Association's Tobacco Regulation Center (ATRAC 2.0) where he is director of the Animal Phenotyping Core and UofL Inhalation Facility.

Dr. Conklin is an author/co-author of over 100 publications including peer-reviewed articles, book chapters and invited reviews. He is a regular grant reviewer of the NIH and the Tobacco Related Disease Research Program (TRDRP), and has been a chair/co-chair of the American Heart Association Great Rivers Affiliate Vascular Biology study section. He is an Associate Editor of Toxicology and Applied Pharmacology since 2007, and an Editorial Board member of Circulation Research since 2015.

Dr. Conklin is a member of the American Heart Association (AHA), American Physiological Society (APS), and the Society of Toxicology (SOT). In the SOT, he is Past-President of the Ohio Valley (OVSOT) SOT Regional Chapter, a Past-President of the Cardiovascular Toxicology Specialty Section (CVTSS), and a current member of the Stem Cell (SCSS), CVTSS, and the Inhalation and Respiratory Specialty Sections (IRSS; former Councilor).

Biosketch

Faculty Webpage

Press & Events

2021


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2016

Positions

Director, Animal Models and Phenotyping Core, Diabetes and Obesity Center, School of Medicine, University of Louisville

Director, Inhalation Facility, School of Medicine, University of Louisville

Professor of Medicine, Division of Cardiovascular Environmental Medicine, Christina Lee Brown Envirome Institute, School of Medicine, Christina Lee Brown Envirome Institute, University of Louisville

Assistant and Associate Professor, 1998-2003, Dr. Conklin was Department of Biological Sciences, University of Wisconsin-Eau Claire

Education

NIEHS Postdoctoral Fellow 1996-1998, University of Texas Medical Branch, Dept. of Pathology, Cardiovascular Toxicology.

Ph.D. 1995, University of Notre Dame, Cardiovascular Physiology.