Sanjay B. Maggirwar, M.B.A., Ph.D.

Sanjay B. Maggirwar, M.B.A., Ph.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 672
Rochester, NY 14642

Research Bio

1. Research Projects in Progress
We are interested in studying abilities of certain cellular proteins to promote survival of neurons exposed to the conditions that mimic disease states. Understanding of intrinsic survival mechanisms in neurons could be highly important in development of new therapeutic strategies for neurological diseases.
A. Inflammatory mechanisms associated with HIV-1 dementia: HIV-1 associated dementia (HAD) is due in part to aberrant activation of brain resident macrophages and microglial cells by viral proteins, causing neuronal dysfunction and death over time.

We hypothesize that CD40 signaling in microglia and in brain microvascular endothelial cells (BMVEC) may synergize with the effects of candidate HIV-1 neurotoxins, such as Tat or platelet activating factor (PAF), and play a pivotal role in HAD. We will investigate this in three specific aims. In Aim 1, we will analyze synergistic effects of candidate HIV-1 neurotoxins and CD40 engagement on inflammatory gene expression in human macrophages and microglial cells, by examining signaling mechanisms associated with CD40 engagement, including analyses of the anti-inflammatory effects of NF-kappaB inhibitors, minocycline and glitazones. In Aim 2, we will examine the role of CD40 engagement in monocyte adhesion and migration through an artificial BBB in response to HIV-1 neurotoxins, by determining specific signaling events that lead to increased expression of adhesion and inflammatory molecules in human BMVEC. Additionally, we will determine whether down-modulation of CD40 expression, following CD40-specific RNA interference or exposure to pharamcologic inhibitors (statins), antagonizes cellular migration through BBB. Finally, in Aim 3, we will use CD40 KO mice, CD40L KO mice or wild-type mice treated with a monoclonal antibody specific for mouse CD40L that disrupts CD40-CD40L interaction, to investigate whether the interplay between CD40- and HIV-1 neurotoxin-mediated signaling also contributes to the CNS inflammation and impaired synaptic transmission in vivo. Collectively, these investigations will identify novel therapeutic strategies that may enhance neuronal function and survival in neuroAIDS.
B. Endogenous mechanisms of neuroprotection: This project uses in vitro rodent and human models to investigate how mixed lineage kinases,(MLKs), acting on pro-apoptotic c-Jun NH2 terminal kinase (JNK), are involved in the activation of mononuclear phagocytes and damage to synaptic architecture. Additionally, this project investigates the functional consequences of MLK3 inhibition in ex vivo brain tissue slices and tests the efficacy of new compounds, synthesized by Biofocus, LTD that inhibit MLK3, to deactivate mononuclear phagocytes, preserve synaptic architecture, and restore synaptic transmission during exposure to HIV-1 neurotoxins.
C. Crosstalk between GSK3beta and NF-kappaB signaling pathway: The overlap between NF-kappaB signaling events and GSK3beta regulation suggests that GSK3beta may be involved in NF-kappaB signaling and that disregulation of GSK3beta activity could potentially disrupt the NF-kappaB response, leading to cell death. Based on this notion, we are investigating, (1) whether HIV toxin Tat-mediated activation of GSK3beta is capable of disrupting activation of endogenous NF-kappaB,; and (2) since overexpression of NF-kappB can prevent cell death induced by Tat, whether it also is able to override toxic effects of irregular activation of GSK3beta.

Awards & Honors (Local)

National Research Fellowship of University Grants Commission, New Delhi, India. 1988 - 1993

Recent Journal Articles

Showing the 5 most recent journal articles. 84 available »

2016
De Jesús Andino F, Jones L, Maggirwar SB, Robert J. "Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction." Scientific reports. 2016 6:22508. Epub 2016 Mar 02.
2016
Jones LD, Jackson JW, Maggirwar SB. "Modeling HIV-1 Induced Neuroinflammation in Mice: Role of Platelets in Mediating Blood-Brain Barrier Dysfunction." PloS one. 2016 11(3):e0151702. Epub 2016 Mar 17.
2016
Singh VB, Singh MV, Gorantla S, Poluektova LY, Maggirwar SB. "Smoothened Agonist Reduces Human Immunodeficiency Virus Type-1-Induced Blood-Brain Barrier Breakdown in Humanized Mice." Scientific reports. 2016 6:26876. Epub 2016 May 31.
2016
Jackson JW, Singh MV, Singh VB, Jones LD, Davidson GA, Ture S, Morrell CN, Schifitto G, Maggirwar SB. "Novel Antiplatelet Activity of Minocycline Involves Inhibition of MLK3-p38 Mitogen Activated Protein Kinase Axis." PloS one. 2016 11(6):e0157115. Epub 2016 Jun 06.
2016
Piepenbrink MS, Samuel M, Zheng B, Carter B, Fucile C, Bunce C, Kiebala M, Khan AA, Thakar J, Maggirwar SB, Morse D, Rosenberg AF, Haughey NJ, Valenti W, Keefer MC, Kobie JJ. "Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users." PloS one. 2016 11(7):e0158641. Epub 2016 Jul 05.

Current Appointments

Vice Chair - Department of Microbiology and Immunology (SMD)
Professor - Department of Microbiology and Immunology (SMD) - Primary

Education

PhD | Biochemistry | India-Univ of Pune, Pune1993
MBA | Marketing | India-Marathwada Univ, Aurangabad1986
MS | Biochemistry | India-Marathwada Univ, Aurangabad1984
BS | Biochemistry | India-Marathwada Univ, Aurangabad1982

Post-Doctoral Training & Residency

Postdoctoral Fellow, Department of Microbiology and Immunology, Pennsylvania State University, College of Medicine, Hershey, PA. 1997
Postdoctoral Fellow, Department of Pharmacology and Toxicology, Southern Illinois University, Springfield, IL. 1994