Education and Training

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

Research Interests

• Daniel Conklin Lab

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

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• Jin L, Richardson A, Lynch J, Lorkiewicz P, Srivastava S, Fryar L, Miller A, Theis W, Shirk G, Bhatnagar A, Srivastava S, Riggs DW, Conklin DJ. Formaldehyde and the Transient Receptor Potential Ankyrin-1 Contribute to Electronic Cigarette Aerosol-induced Endothelial Dysfunction in Mice. Toxicol Sci. 2024 Jul 27:kfae096. doi: 10.1093/toxsci/kfae096. Epub ahead of print. PMID: 39067042.
• Yang JY, Mondéjar-Parreño G, Jahng JWS, Lu Y, Hamburg N, Nadeau KC, Conklin DJ, Liao R, Chandy M, Wu JC. Elucidating effects of the environmental pollutant benzo[a]pyrene [BaP] on cardiac arrhythmogenicity. J Mol Cell Cardiol. 2024 Jun;191:23-26. doi: 10.1016/j.yjmcc.2024.04.013. Epub 2024 Apr 20. PMID: 38648962.
• Chandy M, Hill T 3rd, Jimenez-Tellez N, Wu JC, Sarles SE, Hensel E, Wang Q, Rahman I, Conklin DJ. Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: "What Are the Tools Needed for the Job?" and "Do We Have Them?". Cardiovasc Toxicol. 2024 May;24(5):435-471. doi: 10.1007/s12012-024-09850-9. Epub 2024 Mar 31. PMID: 38555547.
• Asplund H, Dreyer HH, Singhal R, Rouchka EC, O'Toole TE, Haberzettl P, Conklin DJ, Sansbury BE. Exposure to Fine Particulate Matter Air Pollution Disrupts Erythrocyte Turnover. Circ Res. 2024 Apr 26;134(9):1224-1227. doi: 10.1161/CIRCRESAHA.124.324411. Epub 2024 Apr 25. PMID: 38662858; PMCID: PMC11059477.
• Zhao J, Adiele N, Gomes D, Malovichko M, Conklin DJ, Ekuban A, Luo J, Gripshover T, Watson WH, Banerjee M, Smith ML, Rouchka EC, Xu R, Zhang X, Gondim DD, Cave MC, O'Toole TE. Obesogenic polystyrene microplastic exposures disrupt the gut-liver-adipose axis. Toxicol Sci. 2024 Mar 26;198(2):210-220. doi: 10.1093/toxsci/kfae013. PMID: 38291899; PMCID: PMC10964747.
• Xie Z, Sutaria SR, Chen JY, Gao H, Conklin DJ, Keith RJ, Srivastava S, Lorkiewicz P, Bhatnagar A. Evaluation of urinary limonene metabolites as biomarkers of exposure to greenness. Environ Res. 2024 Mar 15;245:117991. doi: 10.1016/j.envres.2023.117991. Epub 2023 Dec 22. PMID: 38141921; PMCID: PMC10922478.
• Abouleisa RRE, Tang XL, Ou Q, Salama AM, Woolard A, Hammouri D, Abdelhafez H, Cayton S, Abdulwali SK, Arai M, Sithu ID, Conklin DJ, Bolli R, Mohamed TMA. Gene therapy encoding cell cycle factors to treat chronic ischemic heart failure in rats. Cardiovasc Res. 2024 Mar 13;120(2):152-163. doi: 10.1093/cvr/cvae002. PMID: 38175760; PMCID: PMC10936750.
• Chandy M, Conklin DJ. Recent advances in the cardiotoxicity of anti-cancer drugs: Navigating the landscape of anthracycline-induced cardiotoxicity. Toxicol Appl Pharmacol. 2024 Jan;482:116791. doi: 10.1016/j.taap.2023.116791. Epub 2023 Dec 14. PMID: 38103743.
• Conklin DJ, Haberzettl P, MacKinlay KG, Murphy D, Jin L, Yuan F, Srivastava S, Bhatnagar A. Aldose Reductase (AR) Mediates and Perivascular Adipose Tissue (PVAT) Modulates Endothelial Dysfunction of Short-Term High-Fat Diet Feeding in Mice. Metabolites. 2023 Nov 24;13(12):1172. doi: 10.3390/metabo13121172. PMID: 38132854; PMCID: PMC10744918.
• Ribble A, Hellmann J, Conklin DJ, Bhatnagar A, Haberzettl P. Fine particulate matter (PM_2.5)-induced pulmonary oxidative stress contributes to increases in glucose intolerance and insulin resistance in a mouse model of circadian dyssynchrony. Sci Total Environ. 2023 Jun 15;877:162934. doi: 10.1016/j.scitotenv.2023.162934. Epub 2023 Mar 18. PMID: 36934930; PMCID: PMC10164116.