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

Contact Information

Phone Numbers

Appointment: (585) 276-3000

Research Labs

Biography

Research

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.

Credentials

Faculty Appointments

Education

1982
BS | India-Marathwada Univ, Aurangabad
Biochemistry

1984
MS | India-Marathwada Univ, Aurangabad
Biochemistry

1986
MBA | India-Marathwada Univ, Aurangabad
Marketing

1993
PhD | India-Univ of Pune, Pune
Biochemistry

Awards

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

Patents

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 15/172,355
Filed: Jun 03, 2016
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 14/876,345
Filed: Oct 06, 2015
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Substituted Pyrrolo [2,3-B] Pyridines as MLK Inhibitors
U.S. Serial #: 14/508,566
Filed: Oct 07, 2014
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
U.S. Serial #: 2011258465
Filed: May 24, 2011
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
U.S. Serial #: 603644
Filed: May 24, 2011
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
U.S. Serial #: 13/698,829
Filed: May 24, 2011
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
U.S. Serial #: 201180036376.2
Filed: May 24, 2011
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Bicyclic Heteroaryl Kinase Inhibitors and Methods of Use
U.S. Serial #: 2013-512166
Filed: May 24, 2011
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Mixed Lineage Kinase (MLK) Inhibitors and Methods of Use
U.S. Serial #: 2,744,498
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 2011-537733
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Substituted Pyrrolo [2,3-B] Pyridines as MLK Inhibitors
U.S. Serial #: 13/131,193
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 200980152665.1
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 2009324894
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 614904
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: MLK Inhibitors and Methods of Use
U.S. Serial #: 2014-232195
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Mixed Lineage Kinase (MLK) Inhibitors and Methods of Use
U.S. Serial #: FR09832359.5
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Mixed Lineage Kinase (MLK) Inhibitors and Methods of Use
U.S. Serial #: DE09832359.5
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Mixed Lineage Kinase (MLK) Inhibitors and Methods of Use
U.S. Serial #: IT09832359.5
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Mixed Lineage Kinase (MLK) Inhibitors and Methods of Use
U.S. Serial #: ES09832359.5
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

Title: Mixed Lineage Kinase (MLK) Inhibitors and Methods of Use
U.S. Serial #: GB09832359.5
Filed: Nov 25, 2009
Invented By: StephenDewhurst, HarrisGelbard, ValGoodfellow, Clifford JohnHarris, ColinLoweth, SanjayMaggirwar, YangXu

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Publications

Journal Articles

10/2017
Connor R, Jones LD, Qiu X, Thakar J, Maggirwar SB. "Frontline Science: c-Myc regulates P-selectin glycoprotein ligand-1 expression in monocytes during HIV-1 infection." Journal of leukocyte biology.. 2017 Oct 0; 102(4):953-964. Epub 2017 Jun 29.

8/29/2017
Singh VB, Singh MV, Piekna-Przybylska D, Gorantla S, Poluektova LY, Maggirwar SB. "Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection." Scientific reports.. 2017 Aug 29; 7(1):9578. Epub 2017 Aug 29.

6/2017
Singh MV, Weber EA, Singh VB, Stirpe NE, Maggirwar SB. "Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer?" Journal of neurovirology.. 2017 Jun 0; 23(3):347-357. Epub 2017 Jan 23.

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