Life Sciences

Dr. Singh has an extensive scientific background in studying molecular mechanisms associated with HIV infection and pathogenesis, genomic imprinting, molecular biology and mouse models of disease. Dr. Singh’s research interests include understanding the underlying molecular mechanisms involved in- i) HIV associated neurological disorder, ii) HIV latency, and iii) Viral infection induced developmental defects. Two of his lab’s major projects are listed below.

Project 1: HIV associated comorbidities (neurological disorders): Introduction of combined antiretroviral therapy (cART) has successfully impeded the development of Acquired Immunodeficiency Syndrome (AIDS) and people infected with HIV are living near-normal life span. Unfortunately, various reasons, including cART toxicity and low, albeit persistent viral reservoirs, put these individuals at a higher risk of developing age associated secondary disorders such as cardiovascular disease, neurological disorder, kidney disease and cancer. Dr. Singh’s recent studies have established that HIV can disrupt Blood-Brain-Barrier (BBB) integrity by specifically downregulating Sonic hedgehog (Shh) signaling in brain. BBB disruption is the key event leading to onset of neuroinflammation fueled by the infiltration of HIV infected/activated immune cells in the brain tissue. Dr. Singh’s ongoing research is focused at acquiring a deeper understanding of the roles played by Shh signaling in regulating brain homeostasis specifically in response to viral infection. This line of work presents potential opportunities to design adjunct therapeutic strategies to alleviate viral infection (e.g. HIV, HTLV, HSV, JC Virus, and Zika) induced neuropathogenesis.

Project 2: Research towards HIV cure: eliminating viral reservoirs: The biggest obstacle in achieving cure for HIV is the latent viral reservoirs which are established very early following the infection. There is an inherent heterogeneity among HIV-1 latent reservoirs presumably due to multiple epigenetic mechanisms that drive viral latency, cellular longevity and modulation of host immune responses. It is for this reason that most of the Latency Reversing Agents (LRAs), which worked wonderfully in vitro, were found to be inefficient at affecting viral reservoirs in vivo. Hence, it is important to identify common downstream targets, which are capable of modulating multiple cellular processes in various cell types - long non-coding RNAs (lncRNAs) are among such effectors. Dr. Singh has initiated a novel line of investigation to study the establishment and maintenance of latency orchestrated by multiple partners, including a select class of noncoding RNAs and intrinsic factors of innate immune response that might be working synergistically to keep the integrated provirus in a repressed state. This investigation is supported by exciting preliminary research that was funded by Center for AIDS Research (CFAR, University of Rochester) in the form of a pilot award to Dr. Singh. Successful completion of this study will identify novel targets and pave the way towards HIV cure by ‘Shock and Kill” approach to eliminate latent reservoir.

RESEARCH GRANTS

1. NIH R15 (AREA) Award (R15AI165295-01A1; 2022-2025; $495,000). Investigating RNA polymerase III driven mechanisms in regulating HIV latency. (Role: PI)
2. NIH Subaward (2021-2022) from The George Washington University ($96,957): Platelet-mediated Neuroinflammatory response to HIV. (Role: PI at ACPHS)
3. Pilot Award (2018-2019) from Center for AIDS Research at URMC ($30,000): Targeting Polymerase III transcribed long noncoding RNAs for reactivation of HIV latency. (Role: PI)
4. Micro grant (2016) from CFAR at URMC ($2500) to perform microarray: Identification of the long noncoding RNAs (lncRNAs) required for establishment and maintenance of HIV latency. (Role: PI)

SCIENTIFIC SERVICES:

• Member of American Society for Virology (Since 2021)
• Member of American Society for Microbiology (Since 2020)
• President Elect, American Society of Microbiologists, Easter New York (ENYASM) Chapter
• Editorial Board member for Scientific reports in the field of infectious diseases.
• Ad-Hoc reviewer for Scientific reports, PLOS One, Journal of Neuroinflammation and BioMed Research International.
• Member of Society on Neuro-Immune Pharmacology (SNIP) since 2013- present.
• Member of Early Career Investigator Award (ECITA) committee for SNIP during 2015-2018.

SELECTED PUBLICATIONS

• Khan Irfan, Worrad Arthur, Singh Meera, Maggirwar Sanjay, Singh Vir*. Human Immunodeficiency Virus-1 exerts its neurotoxic effects by downregulating Sonic hedgehog signaling. Journal of Neurovirology, 2022, Feb 18. doi: 10.1007/s13365-022-01061-8.
• Monocytes complexed to platelets differentiate into functionally defective dendritic cells. Meera Singh, Sumanun Suwunnakorn, Sydney Simpson, Emily Weber, Vir Singh, Pawel Kalinski, Sanjay Maggirwar, Journal of Leukocyte Biology, 2020 July 14.
• A novel mechanism of microvesicle regulation by the anti-viral protein tetherin during HIV infection. Emily Weber, Meera Singh, Vir Singh, Joseph Jackson, Sara Ture, Sumanun Suwunnakorn, Craig Morrell, Sanjay Maggirwar. J. Am Heart Assoc. 2020 Sep;9(17):e015998.
• Ayse Kizilyer, Meera V Singh, Vir B Singh, James Palis, Sanjay B Maggirwar (2018). Inhibition of Tropomyosin Receptor Kinase A Signaling Negatively Regulates Megakaryopoiesis and induces Thrombopoiesis. Sci Rep. 2019 Feb 26;9(1):2781. doi: 10.1038/s41598-019-39385-x.
• 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. Sci Rep. 2017 Aug 29;7 (1):9578. Doi: 10.1038/s41598-017-10241-0. *Corresponding Author
• Vir B. Singh, Sirinapa Sribenja, Kayla E. Wilson, Kristopher M. Attwood, Joanna C. Hillman, Shilpa Pathak and Michael J Higgins. Blocked transcription through KvDMR1results in absence of methylation and gene silencing resembling Beckwith-Wiedmann syndrome. Development 2017 May 15; 144 (10) :1820-1830. doi: 10.1242/dev.145136. Epub 2017 Apr 20.
• Singh MV, Weber EA, Singh VB, Stirpe NE, Maggirwar SB. Preventive and therapeutic challenges in combating Zika virus infection: are we getting any closer? J Neurovirol. 2017 Jan 23.
• 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, June 6; 11(6).
• Vir B. Singh*, Meera V. Singh, Santhi Gorantla, Larisa Y. Poluektova, Sanjay B. Maggirwar (2016). Smoothened agonist reduces Human Immunodeficiency Virus type-1- induced blood brain barrier breakdown in humanized mice. Sci Rep. 2016 May 31; 6:26876. doi: 10.1038/srep26876. *Corresponding Author
• Singh M.V., Donna D.C., Jackson J.W., Singh V.B., Silva J., Ramirez S.H. Maggirwar S.B. Characterization of Platelet-Monocyte Complexes in HIV-1-Infected Individuals: Possible Role in HIV-Associated Neuroinflammation. J. Immunol. 2014, Vol 192 (10). Page 4674-84.

Complete list of published work:  https://www.ncbi.nlm.nih.gov/myncbi/vir.singh.1/bibliography/public/

CONFERENCES AND PRESENTATIONS

• Imran Jamal, Anisha Paudel, Landon Thompson, Michel Abdelmalek, Irfan Khan, Vir B. Singh*. Activation of NRF-2 signaling inhibits the reactivation of HIV-1 in latently infected cells. Keystone Symposium on Viral Immunity: Basic Mechanisms and Therapeutic Applications (June 29-July 2nd, 2022, Keystone, CO).
• Irfan A. khan, Arthur H. Worrad, Meera V. Singh, Sanjay B. Maggirwar, Vir B. Singh. Human Immunodeficiency Virus-1 Tat exerts its neurotoxic effects by downregulating Sonic Hedgehog signaling. 4th International Conference on Neurology and Brain Disorders (Dec. 9-11, 2021, virtual event). (Oral presentation)
• Irfan A. khan, Arthur H. Worrad, Meera V. Singh, Sanjay B. Maggirwar, Vir B. Singh*. Human Immunodeficiency Virus-1 Tat exerts its neurotoxic effects by downregulating Sonic Hedgehog signaling. ENYASM Fall Symposium (October 1st, 2021, virtual event). (Oral presentation)
• Vir B Singh, Meera V Singh, Emily A Weber, Robert A Lopez-Astacio, Danielle M Reid, Sanjay B Maggirwar. HIV-Tat induces its Neurotoxic Effects by Downregulation of Sonic Hedgehog signaling in Brain. HIV & Aging conference, Emory School of Nursing (11-12th April 2019), Atlanta, GA, USA (Oral Presentation).
• Singh V B, Singh M V, Jones L D, Shanthi G, Poluektova L Y, Maggirwar S B. Sonic hedgehog signaling confers neuroprotection in HIV-1 infected humanized mice. 21st Annual conference of the Society of NeuroImmune Pharmacology, April 22-25, 2015. Miami, Florida, USA (Oral Presentation).