Daniel J. Conklin, Ph.D.

Professor of Medicine
University Scholar
Director, Exposure and Phenotyping Core
Editor in Chief, Cardiovascular Toxicology

Education and Training

• Ph.D.: University of Notre Dame, Cardiovascular Physiology
• Postdoctoral Fellowship: NIEHS Toxicology Training Program, University of Texas Medical Branch

Research

Keywords

Air Pollution, Aldehydes, Animal Models of Human Disease, Cardiovascular Toxicology, Environmental Cardiology, Endothelial Dysfunction, Glutathione-S-Transferase, Metabolism, Respiratory Irritants Transient Receptor Potential Ankyrin-1, Volatile Organic Compounds

Summary

Proposed mechanism by which inhaled irritants trigger sensory TRPA1 to alter cardiovascular target
physiology and promote pathophysiological changes such as hypertension

Epidemiological studies reveal that cardiovascular diseases are antagonized by environmental pollutant exposure. The presence of aldehydes in complex air borne mixtures of particulate matter and gases (e.g., burn pit aerosols, smog, tobacco smoke and e-cigarette-derived aerosols, automobile exhaust, wildfire smoke, etc.) is well-documented, but the specific contribution that aldehydes make to the cause of or exacerbation of cardiovascular diseases is unknown. Additional sources of environmental aldehydes include foods and beverages.

Environmental aldehydes can promote oxidative stress, lipid peroxidation, and inflammatory processes. Aldehydes such as the acrolein can be formed from the metabolism of exogenous and endogenous compounds, such as allylamine, cyclophosphamide, and polyamines, within cardiovascular and systemic tissues to further induce injury. Acrolein is a ubiquitous compound that we have found in electronic cigarette smoke and its metabolites are associated with cardiovascular disease risk in both smokers and non-smokers alike.

Our focus on acrolein action in cardiovascular tissues over the past 10 years has shown acrolein can injure the heart and blood vessels, and enhance thrombus formation (blood clotting), in part, via activation of the Transient Receptor Potential Ankyrin-1 (TRPA1) channel. Future studies will focus on uncovering the mechanisms by which acrolein and other aldehydes promote cardiovascular toxicity to better understand how to intervene and to develop regulatory guidelines that protect public health.

Center for Cardiometabolic Science (CCS)

Lab Members

(L-R): Lexiao (Monica) Jin, M.D., Ph.D. (Res. Assoc. Sr.); Alexis Miller, M.S., RLATg;
Dan Conklin, Ph.D.; Heather Stowers, Fenge Li

Summer Research Fellows 2024

(UofL Summer Research Scholar Program [SRSP] and AHA Undergraduate Research)

(L-R): Matthew Junard (M2, SRSP); Ella LaVelle (M2, SRSP); Jacob Baldauf (M2, SRSP); Heather Stowers;
Pierce Bergin (AHA Trainee, junior Univ. KY); Sarah Barnett (junior, UofL)

(L-R): Matthew Junard (M2, SRSP); Jacob Baldauf (M2, SRSP); Sarah Barnett (junior, UofL); Ella LaVelle (M2, SRSP);
Pierce Bergin (AHA Trainee, junior, UK); Alexis Miller, M.S., RLATg

 Previous Graduate Students

Andre Richardson, M.S., Ph.D., Pharmacology & Toxicology

(joined 2015; Masters, 2019; T32 Fellow, 2019-2020; Ph.D., 2022)

Project: Tobacco-derived Aldehydes, Platelets and Thrombosis

Publications: 1) Lynch, J., Jin, L., Richardson, A., et al. 2020. Acute and Chronic Vascular Effects of Inhaled Crotonaldehyde in Mice: Role of TRPA1. Toxicol. Appl. Pharmacol. 115120; 2) Lynch, J., Jin, L., Richardson, A., et al., 2020. Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes? Curr. Hypertension Reports. 22(9):73; 3) Richardson, A., T. Krivokhizhina, P. Lorkiewicz, et al. 2022. Effects of Electronic Cigarette Flavorants on Human Platelet Aggregation Ex Vivo. Toxicol. Reports. (in press). Awards: 1st Place OVSOT (2020); Toxicologist II, Center of Toxicology and Environmental Health (Little Rock, AR)

Lexiao Jin, M.D., Ph.D.,Pharmacology & Toxicology

(joined in 2016; received Ph.D., 2020)

Project: Tobacco-derived Aldehydes and Endothelial Dysfunction

Publications: 1) Lynch, J., Jin, L., Richardson, A., et al., 2020. Acute and Chronic Vascular Effects of Inhaled Crotonaldehyde in Mice: Role of TRPA1. Toxicol. Appl. Pharmacol. 115120 ; 2) Lynch, J., Jin, L., Richardson, A., et al., 2020. Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes? Curr. Hypertension Reports. 22(9):73; 3) Jin, L., J. Lynch, et al., 2020. Crotonaldehyde-induced Vascular Relaxation and Toxicity: Role of Endothelium and Transient Receptor Potential Ankyrin-1 (TRPA1). Toxicol. Appl. Pharmacol. 398:115012. plus 3 other first authored papers from Conklin laboratory...

Awards: A-TRAC Fellowship 2020-2022 (2 yr: $100,000); Res. Assoc. Sr. (ConklinLab)

Jordan Lynch, M.S., Ph.D.,Pharmacology & Toxicology

(joined in 2013; received Ph.D. in 2020)

Project: Tobacco-derived Aldehydes, Circulating Angiogenic Cells and Cardiovascular Disease Risk

Publications: 1) Lynch, J., Jin, L., Richardson, A., et al., 2020. Acute and Chronic Vascular Effects of Inhaled Crotonaldehyde in Mice: Role of TRPA1. Toxicol. Appl. Pharmacol. 115120; 2) Lynch, J., Jin, L., Richardson, A., et al., 2020. Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes? Curr. Hypertension Reports. 22(9):73; 3) Jin, L., J. Lynch, et al., 2020. Crotonaldehyde-induced Vascular Relaxation and Toxicity: Role of Endothelium and Transient Receptor PotentialAnkyrin-1 (TRPA1). Toxicol. Appl. Pharmacol. 398:115012. plus 2 other first authored papers from Conklin laboratory.

Positions and Education

Biography

In 2003, Daniel Conklin, Ph.D., joined the University of Louisville, with Aruni Bhatnagar, Ph.D., and Sanjay Srivastava, Ph.D., to conduct Environmental Cardiology research. He currently is supported by the EPA-funded Superfund Research Center, an FDA-funded R01 of Tobacco Regulatory Science, and a DoD-funded grant to investigate the chronic cardiopulmonary injury of complex aerosols. He is the Director of both the Exposure and Phenotyping Core and the UofL Inhalation Facility in the CCS.

He is an author/co-author of over 150 publications including peer-reviewed articles, book chapters and invited reviews. He is a regular reviewer for the NIH Center of Scientific Review. He is the Editor in Chief of the journal Cardiovascular Toxicology.

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, Past-President of the Cardiovascular Toxicology Specialty Section (CVTSS), and a current member of the Exposure (ESS), CVTSS, and the Inhalation and Respiratory Specialty Sections (IRSS; past Councilor).

Mentoring Philosophy

Each graduate school or post-doctoral trainee develops their project in collaboration with mentor’s guidance. I believe it is critical that trainees think deeply about the problem they want to investigate and then proceed to plan the design of the investigation with oversight and approval of the mentor. It is important to have ownership of your ideas and to commit to a plan. We will both agree to the plan through a literal contract that lays out what each of us will commit to do going forward.

The mentor will provide access to infrastructure, financial and intellectual resources to carry out the work, and the professional training that prepares the mentee for future success (e.g., presentations at national conferences, publications, writing of grants). The trainee will commit their best to the work and to regular (formal and informal) updates to the mentor and the committee and to their intellectual community at large. By planning to reach milestones of achievement together, the mentee-mentor relationship will be mutually supportive of the goal of enhancing personal and intellectual growth through the process and to a successful future.

Current Funding

HT9425-24-1-0596
Project Title: Mechanisms of Inhaled Combustion Product-Induced Cardiopulmonary and Systemic Toxicity
Dates: 06/01/2024-05/31/2026
Total Award: $782,366
Principal Investigator: Conklin, Daniel J.

1R01HL171763-01
Project Title: Cardiopulmonary Toxicity of Electronic Nicotine Delivery Systems
Dates: 12/14/2023-11/30/2028
Total Award: $3,900,000
Principal Investigator: Conklin, Daniel J.

P30ES030283
Project Title: University of Louisville Center for Integrative Environmental Health Sciences
Dates: 07/15/2020-03/31/2026
Total Award: $5,775,000
States (PI)
Co-Investigator, Conklin, Daniel J., Ph.D.

T35ES072923-17
Project Title: Summer Environmental Health Research Training
Dates: 07/15/2021-03/31/2026
Total Award: $250,000
States (PI)
Role: MPI, Conklin, Daniel J., Ph.D.

P42ES023716-06
Project Title: Environmental Exposure and Cardiometabolic Disease
Dates: 08/01/2017 – 03/31/2027
Total Award: $10,861,315
Srivastava (PI)
Co-Investigator, Co-Director, Training Core: Conklin, D.J., Ph.D.

Positions

• Director, Exposures and Phenotyping Core, Center for Cardiometabolic Science, 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, University of Louisville
• University Scholar, School of Medicine, University of Louisville
• Associate Professor, 1998-2003, Department of Biological Sciences, University of Wisconsin-Eau Claire, Eau Clair, WI

 Selected Publications

Contact
	Daniel J. Conklin, Ph.D. Professor of Medicine Christina Lee Brown Envirome Institute School of Medicine, University of Louisville Email
	Ph: 502-852-5836 Mailing Address: 404E, Baxter II 580 South Preston Street Louisville, KY 40202