Daniel J. Conklin, Ph.D.

Professor of Medicine
Core Director, Animal Models and Phenotyping

502-852-5836 E-mail

Education and Training

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

Research Interests

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 (e.g., smog, tobacco smoke, automobile exhaust, etc) is well-documented but the contribution these aldehydes play in causing or exacerbating cardiovascular disease is unknown. Additional sources of environmental aldehydes include foods and beverages. Moreover, environmental aldehydes can induce formation of endogenous aldehydes via oxidative stress and lipid peroxidation, as well as by stimulating inflammatory processes that involve myeloperoxidase-mediated actions. An additional source of endogenous aldehyde exposure is the metabolism of exogenous and endogenous compounds, such as allylamine, cyclophosphamide, and polyamines, within cardiovascular and systemic tissues, which generate a particularly reactive aldehyde -- acrolein. 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, block cardiac preconditioning, enhance thrombus formation, stimulate blood vessel hypercontraction and endothelial dysfunction, and elicit endothelial-dependent relaxation via NO- and EDHF-dependent pathways. Future studies will focus on uncovering the mechanisms of action of acrolein-induced cardiovascular toxicity for developing intervention strategies.

Because metabolism of aldehydes, such as acrolein, is a likely important determinant of acrolein tissue concentration and action we have probed the role of aldehyde metabolizing enzymes as a way to understand the nature of aldehyde-induced cardiotoxicity. Recent studies demonstrate that tissue deficiency of the acrolein-metabolizing enzyme, glutathione-S-transferase (GST), affects the sensitivity of the cardiovascular tissues and extra-cardiac structures, including urinary bladder. These data could help explain how many GST polymorphisms, which are present in human populations, increase the relative risk for cardiovascular disease 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, including the GSTs. Subsequent studies will focus on how GST deficiency increases cardiovascular sensitivity to air pollution and aldehydes.

Featured Publications

Full list (via Pubmed)

  • Lynch J, Jin L, Richardson A, Conklin DJ. Tobacco Smoke and Endothelial Dysfunction: Role of Aldehydes? Curr Hypertens Rep. 2020 Aug 28;22(9):73. doi: 10.1007/s11906-020-01085-7.
  • Miller JM, Meki MH, Ou Q, George SA, Gams A, Abouleisa RRE, Tang XL, Ahern BM, Giridharan GA, El-Baz A, Hill BG, Satin J, Conklin DJ, Moslehi J, Bolli R, Ribeiro AJS, Efimov IR, Mohamed TMA. Heart slice culture system reliably demonstrates clinical drug-related cardiotoxicity. Toxicol Appl Pharmacol. 2020 Aug 30;406:115213. doi: 10.1016/j.taap.2020.115213.
  • Basner M, Riggs DW, Conklin DJ. Environmental Determinants of Hypertension and Diabetes Mellitus: Sounding Off About the Effects of Noise. J Am Heart Assoc. 2020 Mar 17;9(6):e016048. doi: 10.1161/JAHA.120.016048. Epub 2020 Mar 9. PubMed PMID: 32146895.
  • Orimoloye OA, Uddin SMI, Chen LC, Osei AD, Mirbolouk M, Malovichko MV, Sithu ID, Dzaye O, Conklin DJ, Srivastava S, Blaha MJ. Electronic cigarettes and insulin resistance in animals and humans: Results of a controlled animal study and the National Health and Nutrition Examination Survey (NHANES 2013-2016). PLoS One. 2019 Dec 31;14(12):e0226744. doi: 10.1371/journal.pone.0226744. eCollection 2019. PubMed PMID: 31891598; PubMed Central PMCID: PMC6938328.
  • Nystoriak MA, Kilfoil PJ, Lorkiewicz PK, Ramesh B, Kuehl PJ, McDonald J, Bhatnagar A, Conklin DJ. Comparative effects of parent and heated cinnamaldehyde on the function of human iPSC-derived cardiac myocytes. Toxicol In Vitro. 2019 Dec;61:104648. doi: 10.1016/j.tiv.2019.104648. Epub 2019 Sep 10. PubMed PMID: 31518667.
  • Jin L, Lorkiewicz P, Malovichko MV, Bhatnagar A, Srivastava S, Conklin DJ. Acetaldehyde Induces an Endothelium-Dependent Relaxation of Superior Mesenteric Artery: Potential Role in Postprandial Hyperemia. Front Physiol. 2019 Oct 22;10:1315. doi: 10.3389/fphys.2019.01315. eCollection 2019. PubMed PMID: 31695624; PubMed Central PMCID: PMC6817488.
  • Lorkiewicz P, Riggs DW, Keith RJ, Conklin DJ, Xie Z, Sutaria S, Lynch B, Srivastava S, Bhatnagar A. Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco. Nicotine Tob Res. 2019 Aug 19;21(9):1228-1238. doi: 10.1093/ntr/nty089. PubMed PMID: 29868926; PubMed Central PMCID: PMC6698950.
  • Boakye AA, Zhang D, Guo L, Zheng Y, Hoetker D, Zhao J, Posa DK, Ng CK, Zheng H, Kumar A, Kumar V, Wempe MF, Bhatnagar A, Conklin DJ, Baba SP. Carnosine Supplementation Enhances Post Ischemic Hind Limb Revascularization. Front Physiol. 2019 Jul 2;10:751. doi: 10.3389/fphys.2019.00751. eCollection 2019. PubMed PMID: 31312142; PubMed Central PMCID: PMC6614208.
  • Abplanalp W, Haberzettl P, Bhatnagar A, Conklin DJ, O'Toole TE. Carnosine Supplementation Mitigates the Deleterious Effects of Particulate Matter Exposure in Mice. J Am Heart Assoc. 2019 Jul 2;8(13):e013041. doi: 10.1161/JAHA.119.013041. Epub 2019 Jun 25. PubMed PMID: 31234700; PubMed Central PMCID: PMC6662354.
  • Keith RJ, Riggs DW, Conklin DJ, Lorkiewicz P, Srivastava S, Bhatnagar A, DeFilippis AP. Nicotine Metabolism in Adults With Type 2 Diabetes. Nicotine Tob Res. 2019 May 21;21(6):846-849. doi: 10.1093/ntr/ntx214. PubMed PMID: 29059414; PubMed Central PMCID: PMC6528156.
  • Conklin DJ, Guo Y, Nystoriak MA, Jagatheesan G, Obal D, Kilfoil PJ, Hoetker JD, Guo L, Bolli R, Bhatnagar A. TRPA1 channel contributes to myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2019 Apr 1;316(4):H889-H899. doi: 10.1152/ajpheart.00106.2018. Epub 2019 Feb 8. PubMed PMID: 30735434; PubMed Central PMCID: PMC6483018.
  • Conklin DJ, Schick S, Blaha MJ, Carll A, DeFilippis A, Ganz P, Hall ME, Hamburg N, O'Toole T, Reynolds L, Srivastava S, Bhatnagar A. Cardiovascular injury induced by tobacco products: assessment of risk factors and biomarkers of harm. A Tobacco Centers of Regulatory Science compilation. Am J Physiol Heart Circ Physiol. 2019 Apr 1;316(4):H801-H827. doi: 10.1152/ajpheart.00591.2018. Epub 2019 Feb 1. Review. PubMed PMID: 30707616; PubMed Central PMCID: PMC6483019.