Education and Training

Ph.D.: Lucknow University, Chemistry
Postdoctoral Fellowship: University of Texas Medical Branch at Galveston

Research Interests

• Director, University of Louisville Superfund Research Center

Cellular and Molecular Mechanisms of Atherosclerosis: Ongoing studies in Dr. Srivastava's laboratory suggest that aldehydes generated from oxidized lipids, and as precursors of advanced glycation end products cause endothelial cell and macrophage activation. Concentration of these aldehydes and their protein adducts are significantly increased in vascular pathologies, especially atherosclerosis. His studies suggest that aldehyde-induced endoplasmic reticulum, could at least in parts, be involved in the pathogenesis of vascular complications. His studies also show that oxidized lipids and reactive aldehyde induce the expression of micro RNAs which could induce macrophage apoptosis and necrosis, and affect inflammatory signaling. Dr. Srivastava's laboratory has generated genetically altered mice to examine how (a) regulation of aldehyde metabolizing enzymes or exposure to reagent aldehydes exacerbate atherosclerosis; (b) does quenching of aldehydes by small molecular weight compounds prevent murine atherosclerosis; (c) ER-stress associate inflammatory signaling and apoptosis affect atherosclerosis; and (d) micro RNAs affect atherosclerotic lesion progression and plaque characteristics. To examine the species independent effects, recently he has established new LDL receptor-null rat model of atherosclerosis. The LDL receptor-null rats are also obese and glucose intolerant. Feeding the rats a western diet exacerbates obesity, glucose intolerance and atherosclerosis.

Effects of New and Emerging Tobacco Products on Vascular Toxicity and Inflammation: Another thrust area of Dr. Srivastava's research is to examine the effect of new and emerging tobacco products and their constituents on cardiovascular toxicity and inflammation. He is studying how exposure to electronic nicotine delivery devices such as electronic cigarettes, electronic hookah, and oral tobacco products and their constituents, especially reactive aldehydes such as acrolein and nicotine affect blood platelets, circulating immune cells, endothelial progenitor cells, platelet and endothelial microparticles, vascular functions and athrogenesis.

Cardiometabolic Toxicity of Volatile Organic Compounds: Apart from lipid oxidation and heating of tobacco products, reactive aldehydes are also abundant in the environment as a ubiquitous pollutant and generated as a byproduct of the metabolism of other airborne toxicants such as volatile organic compounds (VOCs). Dr. Srivastava has established the NIH-funded University of Louisville Superfund Research Center which studies the Cardiometabolic Toxicity of VOCs. Here, investigators conduct mode-of-action research to unravel critical pathways of toxicity to identify toxicological end-points (cardiometabolic changes) of chemicals (VOCs) found at Superfund and related hazardous waste sites. Using high throughput metabolomic and mass spectrometry approaches, animal experiments, and human population studies Center investigations aid in the discovery and validation of novel biomarkers of both exposure and cardiometabolic injury to provide a foundation for future remediation strategies. Superfund studies at UofL employ state-of-the-art tools to develop pollutant atmospheres for animal exposure and to measure unique and sensitive biological endpoints reflective of cardiometabolic injury. Center investigators create new technologies for detecting VOCs at low environmental levels to enable future exposure assessment activities. 

Featured Publications

• 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.
• Riggs DW, Malovichko MV, Gao H, McGraw KE, Taylor BS, Krivokhizhina T, Rai SN, Keith RJ, Bhatnagar A, Srivastava S. Environmental exposure to volatile organic compounds is associated with endothelial injury. Toxicol Appl Pharmacol. 2022 Feb 15;437:115877. doi: 10.1016/j.taap.2022.115877. Epub 2022 Jan 16. PMID: 35045333.
• Zelko IN, Taylor BS, Das TP, Watson WH, Sithu ID, Wahlang B, Malovichko MV, Cave MC, Srivastava S. Effect of vinyl chloride exposure on cardiometabolic toxicity. Environ Toxicol. 2022 Feb;37(2):245-255. doi: 10.1002/tox.23394. Epub 2021 Oct 30. PMID: 34717031; PMCID: PMC8724461.
• 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.
• Wahlang B, Gripshover TC, Gao H, Krivokhizhina T, Keith RJ, Sithu ID, Rai SN, Bhatnagar A, McClain CJ, Srivastava S, Cave MC. Associations Between Residential Exposure to Volatile Organic Compounds and Liver Injury Markers. Toxicol Sci. 2021 Dec 28;185(1):50-63. doi: 10.1093/toxsci/kfab119. PMID: 34668566; PMCID: PMC8714366.
• 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.
• Majid S, Keith RJ, Fetterman JL, Weisbrod RM, Nystoriak J, Wilson T, Stokes AC, Blaha MJ, Srivastava S, Robertson RM, Bhatnagar A, Hamburg NM. Lipid profiles in users of combustible and electronic cigarettes. Vasc Med. 2021 Oct;26(5):483-488. doi: 10.1177/1358863X211009313. Epub 2021 May 20. PMID: 34013801.
• Pfeiffer JA, Hart JL, Wood LA, Bhatnagar A, Keith RJ, Yeager RA, Smith T, Tomlinson M, Gilkey D, Kerstiens S, Gao H, Srivastava S, Walker KL. The importance of urban planning: Views of greenness and open space is reversely associated with self-reported views and depressive symptoms. Popul Med. 2021 Jul;3:20. doi: 10.18332/popmed/139173. PMID: 34368779; PMCID: PMC8341459.
• McGraw KE, Riggs DW, Rai S, Navas-Acien A, Xie Z, Lorkiewicz P, Lynch J, Zafar N, Krishnasamy S, Taylor KC, Conklin DJ, DeFilippis AP, Srivastava S, Bhatnagar A. Exposure to volatile organic compounds - acrolein, 1,3-butadiene, and crotonaldehyde - is associated with vascular dysfunction. Environ Res. 2021 May;196:110903. doi: 10.1016/j.envres.2021.110903. Epub 2021 Feb 24. PMID: 33636185; PMCID: PMC8119348.
• Jin L, Lynch J, Richardson A, Lorkiewicz P, Srivastava S, Theis W, Shirk G, Hand A, Bhatnagar A, Srivastava S, Conklin DJ. Electronic cigarette solvents, pulmonary irritation, and endothelial dysfunction: role of acetaldehyde and formaldehyde. Am J Physiol Heart Circ Physiol. 2021 Apr 1;320(4):H1510-H1525. doi: 10.1152/ajpheart.00878.2020. Epub 2021 Feb 5. PMID: 33543686; PMCID: PMC8260384.