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

• Yeager R, Keith RJ, Riggs DW, Fleischer D, Browning MHEM, Ossola A, Walker KL, Hart JL, Srivastava S, Rai SN, Smith T, Bhatnagar A. Intra-neighborhood associations between residential greenness and blood pressure. Sci Total Environ. 2024 Oct 10;946:173788. doi: 10.1016/j.scitotenv.2024.173788. Epub 2024 Jun 18. PMID: 38901580.
• 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.
• 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.
• Bhatnagar A, Keith R, Yeager R, Riggs D, Sears C, Bucknum B, Smith T, Fleischer D, Chandler C, Walker KL, Hart JL, Srivastava S, Turner J, Rai S. The Green Heart Project: Objectives, Design, and Methods. medRxiv [Preprint]. 2023 Dec 5:2023.12.05.23299461. doi: 10.1101/2023.12.05.23299461. PMID: 38105951; PMCID: PMC10723507.
• 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.
• Chaudhari M, Zelko I, Lorkiewicz P, Hoetker D, Doelling B, Brittian K, Bhatnagar A, Srivastava S, Baba SP. Metabolic Pathways for Removing Reactive Aldehydes are Diminished in Atrophic Muscle During Heart Failure. Res Sq [Preprint]. 2023 Nov 21:rs.3.rs-3621159. doi: 10.21203/rs.3.rs-3621159/v1. PMID: 38045249; PMCID: PMC10690332.
• Xie Z, Chen JY, Gao H, Keith RJ, Bhatnagar A, Lorkiewicz P, Srivastava S. Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis. Environ Sci Technol. 2023 Jul 25;57(29):10563-10573. doi: 10.1021/acs.est.2c09554. Epub 2023 Jul 11. PMID: 37432892; PMCID: PMC11064822.
• Wahlang B, Gao H, Rai SN, Keith RJ, McClain CJ, Srivastava S, Cave MC, Bhatnagar A. Associations between residential volatile organic compound exposures and liver injury markers: The role of biological sex and race. Environ Res. 2023 Mar 15;221:115228. doi: 10.1016/j.envres.2023.115228. Epub 2023 Jan 4. PMID: 36610539; PMCID: PMC9957966.
• Amraotkar AR, Owolabi US, Malovichko MV, Majid S, Weisbrod RM, Benjamin EJ, Fetterman JL, Hirsch GA, Srivastava S, Poudel R, Robertson RM, Bhatnagar A, Hamburg NM, Keith RJ. Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury. Vasc Med. 2023 Feb;28(1):18-27. doi: 10.1177/1358863X221126205. Epub 2022 Dec 11. PMID: 36503365.
• Cui K, Gao X, Wang B, Wu H, Arulsamy K, Dong Y, Xiao Y, Jiang X, Malovichko MV, Li K, Peng Q, Lu YW, Zhu B, Zheng R, Wong S, Cowan DB, Linton M, Srivastava S, Shi J, Chen K, Chen H. Epsin Nanotherapy Regulates Cholesterol Transport to Fortify Atheroma Regression. Circ Res. 2023 Jan 6;132(1):e22-e42. doi: 10.1161/CIRCRESAHA.122.321723. Epub 2022 Nov 29. PMID: 36444722; PMCID: PMC9822875.