Sanjay Srivastava, Ph.D., FAHA

Professor of Medicine
Distinguished University Scholar
Core Director, Pathology and Bioanalytics

502-852-5834 E-mail

Education and Training

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

Research Interests

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 ubiquitous pollutant and generated as a byproduct of the metabolism of other airborne toxicants such as volatile organic compounds (VOCs). Recently, Dr. Srivastava has established an NIH-funded University of Louisville Superfund Research Center which will study the Cardiometabolic Toxicity of VOCs. Center investigators are conducting mode-of-action research to unravel critical pathways of toxicity and 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 will aid in the discovery and validation of novel biomarkers of both exposure and cardiometabolic injury that would lay the foundation for future remediation strategies. These studies will 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 will create new technologies for detecting VOCs at low environmental levels to enable future exposure assessment activities. Senior Center members will educate and train junior investigators, graduate students and post-doctoral Fellows in the field of environmental science, and promote relevant community awareness and participation to enhance mutual bidirectional understanding of exposure risk and the health effects of exposure. The findings and discoveries of the Center will be transferred to affected communities, end users in public and private sectors, and other stakeholders.

Featured Publications

  • Yeager R, Riggs DW, DeJarnett N, Srivastava S, Lorkiewicz P, Xie Z, Krivokhizhina T, Keith RJ, Srivastava S, Browning MHEM, Zafar N, Krishnasamy S, DeFilippis A, Turner J, Rai SN, Bhatnagar A. Association between residential greenness and exposure to volatile organic compounds. Sci Total Environ. 2020 Mar 10;707:135435. doi: 10.1016/j.scitotenv.2019.135435. Epub 2019 Nov 23. PubMed PMID: 31865083.
  • 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.
  • Ramana KV, Srivastava S, Singhal SS. Lipid Peroxidation Products in Human Health and Disease 2019. Oxid Med Cell Longev. 2019 Nov 27;2019:7147235. doi: 10.1155/2019/7147235. eCollection 2019. PubMed PMID: 31885812; PubMed Central PMCID: PMC6900947.
  • Donde H, Ghare S, Joshi-Barve S, Zhang J, Vadhanam MV, Gobejishvili L, Lorkiewicz P, Srivastava S, McClain CJ, Barve S. Tributyrin Inhibits Ethanol-Induced Epigenetic Repression of CPT-1A and Attenuates Hepatic Steatosis and Injury. Cell Mol Gastroenterol Hepatol. 2019 Oct 22;9(4):569-585. doi: 10.1016/j.jcmgh.2019.10.005. [Epub ahead of print] PubMed PMID: 31654770; PubMed Central PMCID: PMC7078548.
  • 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.
  • 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, 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.
  • Brophy ML, Dong Y, Tao H, Yancey PG, Song K, Zhang K, Wen A, Wu H, Lee Y, Malovichko MV, Sithu SD, Wong S, Yu L, Kocher O, Bischoff J, Srivastava S, Linton MF, Ley K, Chen H. Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation. Circ Res. 2019 Feb 15;124(4):e6-e19. doi: 10.1161/CIRCRESAHA.118.313028. PubMed PMID: 30595089; PubMed Central PMCID: PMC6375743.
  • Abplanalp WT, Wickramasinghe NS, Sithu SD, Conklin DJ, Xie Z, Bhatnagar A, Srivastava S, O'Toole TE. Benzene Exposure Induces Insulin Resistance in Mice. Toxicol Sci. 2019 Feb 1;167(2):426-437. doi: 10.1093/toxsci/kfy252. PubMed PMID: 30346588; PubMed Central PMCID: PMC6358255.