Daniel J. Conklin, Ph.D.

Professor of Medicine
University Scholar
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)

  • Abouleisa RRE, Salama ABM, Ou Q, Tang XL, Solanki M, Guo Y, Nong Y, McNally L, Lorkiewicz PK, Kassem KM, Ahern BM, Choudhary K, Thomas R, Huang Y, Juhardeen HR, Siddique A, Ifthikar Z, Hammad SK, Elbaz AS, Ivey KN, Conklin DJ, Satin J, Hill BG, Srivastava D, Bolli R, Mohamed TMA. Transient Cell Cycle Induction in Cardiomyocytes to Treat Subacute Ischemic Heart Failure. Circulation. 2022 Apr 26;145(17):1339-1355. doi: 10.1161/CIRCULATIONAHA.121.057641. Epub 2022 Jan 21. PMID: 35061545; PMCID: PMC9038650.
  • Zhao J, Gomes D, Jin L, Mathis SP, Li X, Rouchka EC, Bodduluri H, Conklin DJ, O'Toole TE. Polystyrene bead ingestion promotes adiposity and cardiometabolic disease in mice. Ecotoxicol Environ Saf. 2022 Mar 1;232:113239. doi: 10.1016/j.ecoenv.2022.113239. Epub 2022 Jan 29. PMID: 35093814; PMCID: PMC8860873.
  • Lorkiewicz P, Keith R, Lynch J, Jin L, Theis W, Krivokhizhina T, Riggs D, Bhatnagar A, Srivastava S, Conklin DJ. Electronic Cigarette Solvents, JUUL E-Liquids, and Biomarkers of Exposure: In Vivo Evidence for Acrolein and Glycidol in E-Cig-Derived Aerosols. Chem Res Toxicol. 2022 Feb 21;35(2):283-292. doi: 10.1021/acs.chemrestox.1c00328. Epub 2022 Jan 19. PMID: 35044764; PMCID: PMC8864610.
  • Zelko IN, Dassanayaka S, Malovichko MV, Howard CM, Garrett LF, Uchida S, Brittian KR, Conklin DJ, Jones SP, Srivastava S. Chronic Benzene Exposure Aggravates Pressure Overload-Induced Cardiac Dysfunction. Toxicol Sci. 2021 Dec 28;185(1):64-76. doi: 10.1093/toxsci/kfab125. PMID: 34718823; PMCID: PMC8714365.
  • Malovichko MV, Abplanalp WT, McFall SA, Taylor BS, Wickramasinghe NS, Sithu ID, Zelko IN, Uchida S, Hill BG, Sutaria SR, Nantz MH, Bhatnagar A, Conklin DJ, O'Toole TE, Srivastava S. Subclinical markers of cardiovascular toxicity of benzene inhalation in mice. Toxicol Appl Pharmacol. 2021 Nov 15;431:115742. doi: 10.1016/j.taap.2021.115742. Epub 2021 Oct 5. PMID: 34624356; PMCID: PMC8647905.
  • Jin L, Conklin DJ. A novel evaluation of endothelial dysfunction ex vivo: "Teaching an Old Drug a New Trick". Physiol Rep. 2021 Nov;9(21):e15120. doi: 10.14814/phy2.15120. PMID: 34755498; PMCID: PMC8579072.
  • Haberzettl P, Jin L, Riggs DW, Zhao J, O'Toole TE, Conklin DJ. Fine particulate matter air pollution and aortic perivascular adipose tissue: Oxidative stress, leptin, and vascular dysfunction. Physiol Rep. 2021 Aug;9(15):e14980. doi: 10.14814/phy2.14980. PMID: 34327871; PMCID: PMC8322754.
  • Li X, Haberzettl P, Conklin DJ, Bhatnagar A, Rouchka EC, Zhang M, O'Toole TE. Exposure to Fine Particulate Matter Air Pollution Alters mRNA and miRNA Expression in Bone Marrow-Derived Endothelial Progenitor Cells from Mice. Genes (Basel). 2021 Jul 10;12(7):1058. doi: 10.3390/genes12071058. PMID: 34356074; PMCID: PMC8307414.
  • Tevis DS, Flores SR, Kenwood BM, Bhandari D, Jacob P 3rd, Liu J, Lorkiewicz PK, Conklin DJ, Hecht SS, Goniewicz ML, Blount BC, De Jesús VR. Harmonization of acronyms for volatile organic compound metabolites using a standardized naming system. Int J Hyg Environ Health. 2021 Jun;235:113749. doi: 10.1016/j.ijheh.2021.113749. Epub 2021 May 4. PMID: 33962120; PMCID: PMC9019778.
  • Lin Q, Huang Z, Cai G, Fan X, Yan X, Liu Z, Zhao Z, Li J, Li J, Shi H, Kong M, Zheng MH, Conklin DJ, Epstein PN, Wintergerst KA, Mohammadi M, Cai L, Li X, Li Y, Tan Y. Activating Adenosine Monophosphate-Activated Protein Kinase Mediates Fibroblast Growth Factor 1 Protection From Nonalcoholic Fatty Liver Disease in Mice. Hepatology. 2021 Jun;73(6):2206-2222. doi: 10.1002/hep.31568. PMID: 32965675; PMCID: PMC8082952.