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. 74 available »

2014 May 15
Singh MV, Davidson DC, Jackson JW, Singh VB, Silva J, Ramirez SH, Maggirwar SB. "Characterization of platelet-monocyte complexes in HIV-1-infected individuals: possible role in HIV-associated neuroinflammation." The Journal of immunology : official journal of the American Association of Immunologists. 2014 May 15; 192(10):4674-84. Epub 2014 Apr 11.
2013 Jun 1
McMillan DH, Woeller CF, Thatcher TH, Spinelli SL, Maggirwar SB, Sime PJ, Phipps RP. "Attenuation of inflammatory mediator production by the NF-?B member RelB is mediated by microRNA-146a in lung fibroblasts." American journal of physiology. Lung cellular and molecular physiology. 2013 Jun 1; 304(11):L774-81. Epub 2013 Apr 05.
2013 Jun
Ma Q, Gelbard HA, Maggirwar SB, Dewhurst S, Gendelman HE, Peterson DR, Difrancesco R, Hochreiter JS, Morse GD, Schifitto G. "Pharmacokinetic interactions of CEP-1347 and atazanavir in HIV-infected patients." Journal of neurovirology. 2013 Jun; 19(3):254-60. Epub 2013 Jun 05.
2013
Davidson DC, Schifitto G, Maggirwar SB. "Valproic acid inhibits the release of soluble CD40L induced by non-nucleoside reverse transcriptase inhibitors in human immunodeficiency virus infected individuals." PloS one. 2013 8(3):e59950. Epub 2013 Mar 28.
2013
Davidson DC, Jackson JW, Maggirwar SB. "Targeting platelet-derived soluble CD40 ligand: a new treatment strategy for HIV-associated neuroinflammation?" Journal of neuroinflammation. 2013 10:144. Epub 2013 Dec 01.

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