Gatikrushna Singh, PhD

Assistant Professor, Department of Neurosurgery

Gatikrushna Singh

Contact Info

Assistant Professor, Department of Neurosurgery


PhD, RNA Biology and Molecular Virology, International Center for Genetic Engineering and Biotechnology, New Delhi, India

MSc, Biotechnology, Utkal University, Bhubaneswar, India

BSc Honors, Botany, Fakir Mohan University, Balasore, India

Summary

I am addressing a long-standing unanswered question and developing a research project around HIV-induced glioblastoma to identify the role of the virus in inducing the brain cancer. I am also establishing the role that non-coding RNA plays in the development of resistance to radiation treatment for glioblastoma. I use my knowledge of RNA biology and molecular virology to identify drug targets and targeted therapeutics for conditions such as brain cancer related to HIV-AIDS.

Understanding the mechanisms of host pathogen interaction and antiviral response forms the basis of my research. I have characterized mechanisms of antiviral RNA interference and identified anti-viral targets for developing small molecule drugs/inhibitors. I developed the protocols for high-throughput, small molecule drug screening and identified small molecule inhibitors for HIV-AIDS treatment.

My research has identified and characterized novel host RNA-binding protein complexes required for viral protein translation and nucleation of virion ribonucleoproteins (RNPs). Recently, we addressed the long-standing gap in knowledge about how ribosomes are attracted to microRNAs (mRNAs), encoding tumor suppressor and HIV structural proteins. For the first time, we discovered molecular “chaperones” to control the access of ribosomes to tumor suppressor mRNAs. They unveiled nuclear proteins that remain secured for life to these select mRNAs and permit the timely synthesis of tumor suppressor proteins for healthy cell growth.

Our research identified that the nuclear RNA helicase and nuclear cap-binding protein 3 are repurposed to take the place of cytoplasmic regulators that need to be shut down in properly growing cells. I am extending the knowledge to use the RNP complex for drug targets to develop RNA-targeted therapy to control brain cancer and HIV-AIDS.

Research

Patents

  • U.S. provisional patent applications (US 62/852,459): “GA-motifs and uses thereof,” Kathleen Boris-Lawrie and Gatikrushna Singh. Sponsor: University of Minnesota
  • Invention Disclosure (2019), “Novel translation control mechanism and uses thereof,” University of Minnesota Tech Commercialization Office, Kathleen Boris-Lawrie and Gatikrushna Singh 

Publications

Publications (most recent)

Singh G, Seufzer B, Song Z, Heng X, Boris-Lawrie K.Host non-canonical ribonucleoprotein interactions are necessary for virion late protein synthesis.PNAS.2021. In Press

Song Z, Gremminger T,Singh G, Cheng Y, Li J, Qiu L, Ji J, Lange MJ, Zuo X, Chen S, Zou X, Boris-Lawrie K and Heng X. Structure of HIV-1 PBS-segment is necessary for reverse transcriptase activity and conserved for viral infectivity.Nucleic Acids Res.2021. In Press

Singh G,Singh D, Placek N, Hull S, Sura R,Boris-Lawrie K. The appropriate ratio of retroviral structural proteins is activated by the spleen necrosis virus post-transcriptional control element.Nanotechnology. 2021. In Press

Osmer P,Singh G, Boris-Lawrie K. A new approach to 3D modeling: of inhomogeneous populations of viral regulatory RNA.Viruses.(2020) 12, 1108; doi:10.3390/v12101108. (Cover feature to special issue)

Singh G, Fritz SE, Seufzer B, Boris-Lawrie K. The mRNA encoding the JUND tumor suppressor detains nuclear RNA-binding proteins to assemble polysomes that are unaffected by mTOR. J Biol Chem.(2020) 295: 7763-7773. (Featured inTrends Biochem Sci.2020 Oct 5; doi: 10.1016/j.tibs.2020.09.003)

Brady S,Singh G, Bolinger C, Song Z, Boeras I, Weng K, Trent B, Brown WC, Singh K, Boris-Lawrie K, Heng X. Virion-associated, host-derived DHX9/RNA helicase A enhances the processivity of HIV-1 reverse transcriptase on genomic RNA.J Biol Chem.(2019) 294:11473-11485

Chao TC, Zhang Q, Li Z, Tiwari SK, Qin Y, Yau E, Sanchez A, Singh G, Chang K, Kaul M, Karris M, Rana TM. The Long Noncoding RNA HEAL Regulates HIV-1 Replication through Epigenetic Regulation of the HIV-1 Promoter.mBio.(2019) doi: 10.1128/mBio.02016-19

Sharkey M, Sharova N, Mohammed I, Huff SE, Kummetha IR,Singh G, Rana TM, Stevenson M.HIV-1 Escape from Small-Molecule Antagonism of Vif.mBio.(2019) doi: 10.1128/mBio.00144-19

Singh G, Rife B, Seufzer B, Salemi M, Rendahl A and Boris-Lawrie K. Identification of conserved, primary sequence motifs that direct retrovirus RNA fate.Nucleic Acids Res.(2018) 46:7366-7378

Singh G, Heng X, Boris-Lawrie K. Nuclear RNA helicases support early and late events in retroviral replication.Retrovirus-Cell Interactions.(2018) 10.1016/B978-0-12-811185-7

Singh G, Fritz SM, Ranji A, Singh D, Boris-Lawrie K. Isolation of cognate RNA-protein complexes from cells using oligonucleotide-directed elution.J. Vis. Exp.(2017) 119: 54391, doi:10.3791/54391.

Mohammed I, Kummetha IR,Singh G, Sharova N, Lichinchi G, Dang J, Stevenson M, Rana TM. 1,2,3-Triazoles as amide bioisosteres: Discovery of a new class of HIV-1 Vif antaonists. J. Med. Chem (2016) 59: 7677-7682

Ghosh S,Singh G, Sachdev B, Kumar A, Malhotra P, Mukherjee SK, Bhatnagar RK. RNAi Screening inSpodoptera frugiperda.Methods Mol. Biol.(2016) 1470: 199-212

Singh D, Boeras I,Singh Gand Boris-Lawrie K. Isolation of cognate cellular and viral ribonucleoprotein complexes of HIV-1 RNA applicable to proteomic discovery and molecular investigations.Methods Mol. Biol.(2016) 1354: 133–146

Stake M, Singh D,Singh G, Hernandez M, Kaddis R, Parent L and Boris-Lawrie K. HIV-1 and two genetically simpler avian retrovirus 5' untranslated regions bind orthologous human and chicken RNA binding proteins.Virology(2015) 486: 307-320

Mohammed I, Parai MK, Jiang X, Sharova N,Singh G, Stevenson M and Rana TM. SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor.ACS Med. Chem. Lett. (2012) 3: 465-469.

Complete publication list

Invited presentations (selected)

Hypermethylation of HIV-1 RNAs represents a regulatory mechanism for selective expression co-opted from host stress response. Cold Spring Harbor Laboratory Retroviruses meeting, 05-25-2021

Balance expression of HIV mRNAs regulate viral pathogenicity. Cold Spring Harbor Laboratory Retroviruses meeting, 05-16-2020

RNA based antiviral therapy. Veterinary Biomedical Sciences, University of Minnesota, 06-18-2019

GA-rich motifs in HIV 5’UTR necessary for balanced expression HIV RNA. National Institute Health Structural Biology Meeting, 06-23-2016

Discovery of retrovirus- host factor interaction necessary for nucleation of viral particle. Veterinary Biomedical Sciences, University of Minnesota, 03-23-2016

Host factor regulates the expression of HIV genomic RNA. Cold Spring Harbor Laboratory Retroviruses meeting, 05-14-2015

Vif antagonists rescue host restriction factor APOBEC3G and reduce HIV infection. The Ohio State University, 02-13-2014

Discovery and mechanism of Vif antagonist reduce HIV production. Albert Einstein College of Medicine, New York, 07-24-2013.