KUMAR, SANTOSH

Associate Professor
Pharmaceutical Sciences

Office: 456 COLLEGE OF PHARMACY BUILDING
881 MADISON AVENUE
MEMPHIS TN 381632198
Tel: (901) 448-7157
ksantosh@uthsc.edu

Education

  • Academic Leadership Fellow, American Association of College of Pharmacy, Academic Leadership
  • Associate Professor, University of Tennessee Health Science Center, Pharmaceutical Sciences
  • Assistant Professor, University of Missouri-Kansas City, Pharmacology and Toxicology
  • Research Assistant Professor, University of Texas Medical Branch, Pharmacology and Toxicology
  • Research Instructor, University of Texas Medical Branch, Pharmacology and Toxicology
  • PostDoc, University of Missouri-Kansas City, Biological sciences
  • Ph.D., Indian Institute of Technology, Biotechnology
  • M.S., Indian Institute of Technology, Biotechnology

Download My Curriculum Vitae

Research Keywords

HIV, Alcohol, Smoking, Exosomes, Cytochrome P450

Research Description

1. Alcohol, HIV, antiretroviral therapy (ART), and CYP: Since alcohol and many ARTs such as non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are metabolized by the CYP family of enzymes, causing oxidative stress and drug-drug interactions, our group developed a research niche in alcohol and HIV. Alcohol use is highly prevalent in HIV populations, and it is known to increase HIV replication and decrease response to ART drugs. In this project, our group has shown the1) potential involvement of CYP pathways in alcohol-PI interactions, which may alter efficacy of ART and ART-mediated toxicity in HIV-infected individuals, 2) mechanism by which CYP2E1 (an alcohol-metabolizing enzyme) is regulated by ethanol in monocytic and astrocytic cell lines, 3) potential role of CYP and oxidative stress pathways in alcohol-mediated HIV pathogenesis using in vitro models and ex-vivo human subjects, and 4) role of CYP enzymes in alcohol-mediated effects on bioavailability of protease and integrase inhibitors. 2. Tobacco/nicotine, HIV, and CYP: Since smoking constituents such as nicotine and polyaromatic hydrocarbons (PAHs) are metabolized by the CYP family of enzymes causing oxidative stress, we developed a research niche in tobacco/nicotine and HIV. Smoking is highly prevalent in HIV populations, and it is known to increase HIV replication. In this project, our laboratory has shown the: 1) potential involvement of CYP pathways in nicotine-mediated oxidative stress in HIV systems, monocytic and astrocytic cell lines, 2) role of CYP-mediated nicotine metabolism and oxidative stress pathways in HIV replication using an ex-vivo study that utilized HIV-infected smokers, 3) potential involvement of cigarette smoke condensate (CSC) and PAHs, especially benzo(a)pyrene, in smoking mediated oxidative stress and cellular toxicity, perhaps through CYP pathways that may lead to HIV pathogenesis. 3. Exosomes, HIV, drugs of abuse, and exosomes. Exosomes are clinically relevant in developing biological markers and novel therapeutics for many diseases. The known role of exosomes in the context of drugs of abuse and HIV is poorly understood. We propose that exosomes derived from macrophages and microglia play an important role in drugs of abuse, especially smoking- and alcohol- mediated effects on HIV pathogenesis and neuronal damage. We also propose that exosomal CYPs, antioxidant and pro-oxidant enzymes, and cytokines, as well as miRNAs that regulate these enzymes, play important role in such effects. This project is funded by NIH/NIDA R21. In this project, we are investigating the potential role of exosomal CYP, AOE, and cytokines in smoking-mediated cytotoxicity and HIV-1 pathogenesis. Further, we plan to identify and characterize the specific contents (e.g. protein, cytokine, miRNA, metabolic contents) in exosomes which might be responsible for tobacco-exacerbated HIV replication and neuronal damage that have clinical relevance to neuro-AIDS. In this project, we also plan to examine the potential role of exosomal enzymes (cathepsins B and D) in mediating alcohol-induced neurotoxicity. 4. Antiretroviral therapy (ART) and nanoformulations: Monocytes serve as sanctuary sites for HIV from which the virus is difficult to be eliminated. Therefore, an effective ART strategy is critical for effective viral suppression in monocytes. This study focuses on a new strategy using nanoformulation to optimize the efficacy of ART drugs in HIV-infected monocytes, with the ability to cross the blood-brain barrier to improve HIV treatment outcomes. In this project: 1) we developed a PLGA-EVG nanoparticle formulation which demonstrated time- and concentration-dependent uptakes in monocytes and superior viral suppression for a prolonged period of time in HIV-infected macrophages. We are now in the process of using these nanoparticles to specifically target monocytes and to examine their role in infiltrating the BBB and suppressing HIV in CNS cells.

Research Interest/Specialty

Our research program is at the intersection of HIV-1, drugs of abuse, cytochrome P450, and exosomes. Drugs of abuse, especially alcohol drinking and tobacco smoking are highly prevalent in HIV-infected individuals. Alcohol and tobacco are known to augment HIV replication and reduce the response to antiretroviral therapy leading to exacerbated HIV pathogenesis and AIDS/NeuroAIDS. However, the mechanisms by which these phenomena occur are largely unknown. We propose that alcohol- and tobacco-mediated increases in HIV replication and decreases in the response to antiretroviral therapy occur through the cytochrome P450 (CYP) pathway. Our ongoing projects are to study the “role of CYP in alcohol- and tobacco-mediated HIV-1 pathogenesis and antiretroviral therapy”. The alcohol project is funded by NIH/NIAAA. Our group is the first one to show a potential role of CYP pathways within the context of drugs of abuse-mediated HIV pathogenesis. This provides a novel target to treat HIV-infected drug abusers effectively.

Research/Scholarly Activities

Background
·         Profile
o   Honors (2014)
“Mahatma Gandhi Pravasi (Non-resident Indian (NRI)) Samman (Honor)”, New Delhi, India
“Teacher of the Year Award” runner up from the class of 2016, School of Pharmacy, UMKC
 
·         Education/Training/Employment
BS: Chemistry honors, Delhi University
MS: Biotechnology, Indian Institute of Technology-Bombay
PhD: Biotechnology, Indian Institute of Technology-Bombay
PDF: Biochemistry and Cell Biology, University of Missouri-Kansas City
Research Instructor and Research Assistant Professor: Pharmacology and Toxicology, University of Texas Medical Branch
Assistant Professor: Pharmacology and Toxicology, University of Missouri-Kansas City
 
Research/Scholarly Activities
H-index - 19
·         Research/Scholarly Activities Profile
o   Research Interest/Specialty: Effect of substance abuse in HIV-infected individuals, Role of cytochrome P450 in drug metabolism and drug-drug interaction
o   Research Keywords: HIV, alcohol, smoking, cytochrome P450, drug metabolism, drug interaction, oxidative stress
o   Research Description: Dr. Kumar research interest includes “Effect of alcohol and tobacco consumptions on HIV-1 and antiretroviral therapy”. His research is funded by the National Institute of Health. Alcohol drinking and tobacco smoking are highly prevalent in HIV-1-infected populations. These substances are known to enhance HIV-1 replication and decrease response to antiretroviral therapy. However, the mechanism by which these occur is not known. The hypothesis is that the alcohol and tobacco-mediated effects occur through cytochrome P450 and oxidative stress pathways. Dr. Kumar’s team uses in vitro as well as ex vivo (clinical samples) to test the hypothesis. The research has potential to develop novel interventions and help adjust drugs dose regimen for HIV-infected drinkers and smokers.
 

Publications

  1. Rahman, MA, Gong, Y, Kumar, S. In vitro evaluation of structural analogs of diallyl sulfide as novel CYP2E1 inhibitors for their protective effect against xenobiotic-induced toxicity and HIV replication. Toxicol Lett, 292, 31-38, 2018.
  2. Ranjit, S, Sinha, N, Kodidela, S, Kumar, S. Benzo(a)pyrene in Cigarette Smoke Enhances HIV-1 Replication through NF-κB Activation via CYP-Mediated Oxidative Stress Pathway. Sci Rep, 8 (1), 10394, 2018.
  3. Li, JJ, Wang, B, Kodali, MC, Chen, C, Kim, E, Patters, BJ, Lan, L, Kumar, S, Wang, X, Yue, J, Liao, FF. In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J Neuroinflammation, 15 (1), 8, 2018.
  4. Haque, S, Sinha, N, Ranjit, S, Midde, NM, Kashanchi, F, Kumar, S. Monocyte-derived exosomes upon exposure to cigarette smoke condensate alter their characteristics and show protective effect against cytotoxicity and HIV-1 replication. Sci Rep, 7 (1), 16120, 2017.
  5. Cao, L, Glazyrin, A, Kumar, S, Kumar, A. Role of Autophagy in HIV Pathogenesis and Drug Abuse. Mol Neurobiol, 54 (8), 5855-5867, 2017.
  6. Midde, NM, Gong, Y, Cory, TJ, Li, J, Meibohm, B, Li, W, Kumar, S. Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies. Pharm Res, 34 (9), 1925-1933, 2017.
  7. Rao, PS, Midde, NM, Miller, DD, Chauhan, S, Kumar, A, Kumar, S. Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1. Curr Drug Metab, 16 (6), 486-503, 2015.
  8. Kumar, S, Rao, PS, Earla, R, Kumar, A. Drug-drug interactions between anti-retroviral therapies and drugs of abuse in HIV systems. Expert Opin Drug Metab Toxicol, 11 (3), 343-55, 2015.