KUMAR, SANTOSH

Professor
Pharmaceutical Sciences

Office: 456 COLLEGE OF PHARMACY BUILDING
881 MADISON AVENUE
MEMPHIS TN 381632198
Tel: (901) 448-7157
ksantosh@uthsc.edu
https://academic.uthsc.edu/faculty/facepage.php?netID=ksantosh

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

Current lab personnel

Dr. Sunitha Kodidela

Ms. Sanjana Haque

Ms. Yuqing Gong

Ms. Kelli Gerth

Ms. Namita Sinha

NIH-funded grants

 1. R01 (NCE) (PI: Kumar, S)        until 08/2019

National Institute of Alcohol Addiction and Alcoholism (NIAAA)

Title: Role of cytochrome P450 in alcohol-mediated HIV-1 pathogenesis and antiretroviral therapy

2. R01 (Contact PI: Kumar, S)       until 06/2023  

National Institute of Drug Abuse (NIDA)     Parent announcement

Title: Monocytic and plasma exosomal cytochrome P450s in smoking-mediated HIV-1 pathogenesis

Link for bibliography

 https://scholar.google.com/citations?hl=en&user=fMMHne8AAAAJ

https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/

Honors and Awards

At UTHSC

Outstanding Service and Support Award, Society of Neuroimmune Pharmacology (2015)

Elected as “Secretary” of the Society on Neuroimmune Pharmacology (2015-2018)

Kumar-Cory Research highlights, “Through TEAMwork, everyone achieves more.” UTHSC-College of Pharmacy Magazine, 2016

Postdoctoral Fellow Outstanding Junior Mentoring Academy Award, CGHS, UTHSC, 2016

Phi Delta Chi (PDC) “Professor of the Year Award” for 2017-18, COP, UTHSC

UT Alumni Association “Outstanding Teacher Award”, UTHSC, 2018

The Student Government Association Executive Council (SGAEC) “Excellence in Teaching Award”, College of Graduate Health Science, UTHSC, 2018

Phi Delta Chi (PDC) “Professor of the Year Award” for 2018-19, COP, UTHSC

Inducted in Phi Lambda Sigma society, COP, UTHSC, 2019

Distinguish Service Award, Society on Neuroimmune Pharmacology, 2019

Elected as “President-elect” of the Society on Neuroimmune Pharmacology (2019-2021)

Prior to UTHSC

 “Teacher of the Year award” Runner up from the class of 2015, School of Pharmacy, UMKC

Mahatma Gandhi Pravasi (Non-resident Indian (NRI)) Samman (Honor). This is presented to handful of NRIs every year to recognize their contribution in the field.    

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.

Publications

  1. Narasimhan, V, Siddique, RH, Hoffmann, M, Kumar, S, Choo, H. Enhanced broadband fluorescence detection of nucleic acids using multipolar gap-plasmons on biomimetic Au metasurfaces. Nanoscale, 2019.
  2. Kodidela, S, Wang, Y, Patters, BJ, Gong, Y, Sinha, N, Ranjit, S, Gerth, K, Haque, S, Cory, T, McArthur, C, Kumar, A, Wan, JY, Kumar, S. Proteomic Profiling of Exosomes Derived from Plasma of HIV-Infected Alcohol Drinkers and Cigarette Smokers. J Neuroimmune Pharmacol, 2019.
  3. Gong, Y, Haque, S, Chowdhury, P, Cory, TJ, Kodidela, S, Yallapu, MM, Norwood, JM, Kumar, S. Pharmacokinetics and pharmacodynamics of cytochrome P450 inhibitors for HIV treatment. Expert Opin Drug Metab Toxicol, 15 (5), 417-427, 2019.
  4. Rahman, MA, Kodidela, S, Sinha, N, Haque, S, Shukla, PK, Rao, R, Kumar, S. Plasma exosomes exacerbate alcohol- and acetaminophen-induced toxicity via CYP2E1 pathway. Sci Rep, 9 (1), 6571, 2019.
  5. Rahman, MA, Patters, BJ, Kodidela, S, Kumar, S. Extracellular Vesicles: Intercellular Mediators in Alcohol-Induced Pathologies. J Neuroimmune Pharmacol, 2019.
  6. Kodidela, S, Kumar, S. Choosing the right pharmacotherapeutic strategy for HIV maintenance in patients with alcohol addiction. Expert Opin Pharmacother, 20 (6), 631-633, 2019.
  7. Hatami, E, Mu, Y, Shields, DN, Chauhan, SC, Kumar, S, Cory, TJ, Yallapu, MM. Mannose-decorated hybrid nanoparticles for enhanced macrophage targeting. Biochem Biophys Rep, 17, 197-207, 2019.
  8. Gong, Y, Rao, PSS, Sinha, N, Ranjit, S, Cory, TJ, Kumar, S. The role of cytochrome P450 2E1 on ethanol-mediated oxidative stress and HIV replication in human monocyte-derived macrophages. Biochem Biophys Rep, 17, 65-70, 2019.
  9. Mu, Y, Patters, BJ, Midde, NM, He, H, Kumar, S, Cory, TJ. Tobacco and Antiretrovirals Modulate Transporter, Metabolic Enzyme, and Antioxidant Enzyme Expression and Function in Polarized Macrophages. Curr HIV Res, 16 (5), 354-363, 2018.
  10. 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.
  11. 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.
  12. Ranjit, S, Kumar, S. Recent advances in cancer outcomes in HIV-positive smokers. F1000Res, 7, 2018.
  13. Kodidela, S, Ranjit, S, Sinha, N, McArthur, C, Kumar, A, Kumar, S. Cytokine profiling of exosomes derived from the plasma of HIV-infected alcohol drinkers and cigarette smokers. PLoS One, 13 (7), e0201144, 2018.
  14. 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.
  15. He, H, Buckley, M, Britton, B, Mu, Y, Warner, K, Kumar, S, Cory, TJ. Polarized macrophage subsets differentially express the drug efflux transporters MRP1 and BCRP, resulting in altered HIV production. Antivir Chem Chemother, 26, 2040206617745168, 2018.
  16. Gong, Y, Chowdhury, P, Midde, NM, Rahman, MA, Yallapu, MM, Kumar, S. Novel elvitegravir nanoformulation approach to suppress the viral load in HIV-infected macrophages. Biochem Biophys Rep, 12, 214-219, 2017.
  17. 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.
  18. Cao, L, Glazyrin, A, Kumar, S, Kumar, A. Role of Autophagy in HIV Pathogenesis and Drug Abuse. Mol Neurobiol, 54 (8), 5855-5867, 2017.
  19. 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.
  20. Midde, NM, Sinha, N, Lukka, PB, Meibohm, B, Kumar, S. Alterations in cellular pharmacokinetics and pharmacodynamics of elvitegravir in response to ethanol exposure in HIV-1 infected monocytic (U1) cells. PLoS One, 12 (2), e0172628, 2016.
  21. Rao, PS, Kumar, S. Chronic Effects of Ethanol and/or Darunavir/Ritonavir on U937 Monocytic Cells: Regulation of Cytochrome P450 and Antioxidant Enzymes, Oxidative Stress, and Cytotoxicity. Alcohol Clin Exp Res, 40 (1), 73-82, 2016.
  22. Midde, NM, Kumar, S. Development of NanoART for HIV Treatment: Minding the Cytochrome P450 (CYP) Enzymes. J Pers Nanomed, 1 (1), 24-32, 2015.
  23. Rao, P, Ande, A, Sinha, N, Kumar, A, Kumar, S. Effects of Cigarette Smoke Condensate on Oxidative Stress, Apoptotic Cell Death, and HIV Replication in Human Monocytic Cells. PLoS One, 11 (5), e0155791, 2015.
  24. Nookala, AR, Li, J, Ande, A, Wang, L, Vaidya, NK, Li, W, Kumar, S, Kumar, A. Effect of Methamphetamine on Spectral Binding, Ligand Docking and Metabolism of Anti-HIV Drugs with CYP3A4. PLoS One, 11 (1), e0146529, 2015.
  25. Midde, NM, Rahman, MA, Rathi, C, Li, J, Meibohm, B, Li, W, Kumar, S. Effect of Ethanol on the Metabolic Characteristics of HIV-1 Integrase Inhibitor Elvitegravir and Elvitegravir/Cobicistat with CYP3A: An Analysis Using a Newly Developed LC-MS/MS Method. PLoS One, 11 (2), e0149225, 2015.
  26. Ande, A, Sinha, N, Rao, PS, McArthur, CP, Ayuk, L, Achu, PN, Njinda, A, Kumar, A, Kumar, S. Enhanced oxidative stress by alcohol use in HIV+ patients: possible involvement of cytochrome P450 2E1 and antioxidant enzymes. AIDS Res Ther, 12, 29, 2015.
  27. 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.
  28. Rao, PS, Kumar, S. Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis. Front Microbiol, 6, 550, 2015.
  29. 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.
  30. Ande, A, McArthur, C, Ayuk, L, Awasom, C, Achu, PN, Njinda, A, Sinha, N, Rao, PS, Agudelo, M, Nookala, AR, Simon, S, Kumar, A, Kumar, S. Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals. PLoS One, 10 (4), e0122402, 2014.