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Kushol Gupta, PhD

KUSHOL GUPTA, Ph.D.

Research Assistant Professor of Biochemistry and Biophysics

810 Stellar-Chance Laboratories
422 Curie Blvd
Philadelphia, PA 19104
215-573-7260
267-259-0082
kgupta@upenn.edu

Ph.D. University of Pennyslvania (2003) Pharmacology

pubmed

DESCRIPTION OF RESEARCH INTERESTS:

Dr. Gupta's research is broadly focused on the study of macromolecular assemblies that regulate genetic information. His studies have included the viral proteins that mediate lateral DNA transfer (including retroviral integrases and phage-encoded site-specific recombinases), chromatin structure, and large assemblies involved in RNA-related processes (including the Survival of Motor Neutron (SMN) complex, bacterial Group II introns, and the 70S Ribosome). Alongside X-ray crystallography, his research has extensively leveraged solution-based methods, including small-angle x-ray and neutron scattering (SAXS/SANS), analytical ultracentrifugation (AUC), and size-exclusion chromatography in-line with multi-angle light scattering (SEC-MALS), to test structural models and gain insight into fundamental questions about quaternary structure, stoichiometry, and oligomerization. 

Retroviral Integrase. Through 2013, it has been estimated that over 35 million individuals worldwide were living with HIV/AIDS, with ~2.3 million new infections per year and ~1.6 million annual deaths due to the syndrome itself. The constant emergence of drug resistance in the clinic continues to underscore the importance of identifying novel drug targets. Dr. Gupta’s study of retroviral integrase (IN) is part of a long-time collaboration between the laboratories of Gregory Van Duyne (BMB) and Frederic Bushman (Microbiology) at Penn.

After infection, a large megadalton assembly comprised of newly-synthesized viral cDNA, preformed viral proteins, and host proteins is transported across the nuclear pore complex to chromatin, where it then carries out the integration of the viral cDNA into the host chromatin at intact nucleosomes, resulting in the formation of new provirus. The catalytic component of this assembly is the viral protein integrase (IN), one of only three enzymes encoded for in the HIV genome. Dr. Gupta’s contributions to this area has included studies of the allosteric inhibition of HIV Integrase (IN), the higher-order quaternary structure and oligomeric properties of retroviral integrases, and the association of retroviral IN and related nucleoprotein assembles with host factors such as LEDGF/p75 and Transportin. 

Recent Publications

Arturo EC, Gupta K, Heroux A, Stith L, Cross PJ, Parker EJ, Loll PJ, Jaffe EK (2016) First structure of full-length mammalian phenylalanine hydroxylase reveals the architecture of an autoinhibited tetramer. Proceedings of the National Academy of Sciences of the United States of America 2016 Feb 15 [Epub ahead of print]. 

Fuglestad B, Gupta K, Wand AJ, Sharp KA (2016) Characterization of cetyl trimethylammonium bromide/hexanol reverse micelles by experimentally benchmarked molecular dynamics simulations. Langmuir 2016 Feb 3 [Epub ahead of print].  

Gupta K, Martin R, Sharp R, Sarachan KL, Ninan NS, Van Duyne GD (2015) Oligomeric properties of survival motor neuron·gemin2 complexes.The Journal of Biological Chemistry 290(33):20185-20199.

Falk SJ, Guo LY, Sekulic N, Smoak EM, Mani T, Logsdon GA, Gupta K, Jansen LET, Van Duyne GD, Vinogradov SA, Lampson MA, Black BE (2015) Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere. Science 348(6235):699-703.

Sweeny EA, Jackrel ME, Go MS, Sochor MA, Razzo BM, DeSantis ME, Gupta K, Shorter J (2015) The Hsp104 N-terminal domain enables disaggregase plasticity and potentiation.  Molecular Cell 57(5):836-849.

Gupta K, Selinsky BS (2015) Bacterial and algal orthologs of prostaglandin H₂synthase: novel insights into the evolution of an integral membrane protein. Biochimica et Biophysica Acta 1848(1 Pt A):83-94.

Tao Z, Fusco A, Huang DB, Gupta K, Young KD, Ware CF, Van Duyne GD, Ghosh Gourisankar (2014) p100/IκBδ sequesters and inhibits NF-κB through kappaBsome formation. Proceedings of the National Academy of Sciences of the United States of America 111(45):15946-15951.

Gupta K, Brady T, Dyer BM, Malani N, Hwang Y, Male F, Nolte RT, Wang L, Velthuisen E, Jeffrey J, Van Duyne GD, Bushman FD (2014) Allosteric inhibition of human immunodeficiency virus integrase: late block during viral replication and abnormal multimerization involving specific protein domains. The Journal of Biological Chemistry 289(30):20477-20488.

Gupta K, Contreras LM, Smith D, Qu G, Huang T, Spruce LA, Seeholzer SH, Belfort M, Van Duyne GD (2014) Quaternary arrangement of an active, native group II intron ribonucleoprotein complex revealed by small-angle X-ray scattering. Nucleic Acids Research 42(8):5347-5360.

Desantis ME, Sweeny EA, Snead D, Leung EH, Go MS, Gupta K, Wendler P, Shorter J (2014) Conserved distal loop residues in the Hsp104 and ClpB middle domain contact nucleotide-binding domain 2 and enable Hsp70-dependent protein disaggregation. The Journal of Biological Chemistry 289(2):848-867.

Martin R, Gupta K, Ninan NS, Perry K, Van Duyne GD (2012)The survival motor neuron protein forms soluble glycine zipper oligomers. Structure (London, England:1993) 20(11):1929-1939.

Gupta K, Curtis JE, Krueger S, Hwang Y, Cherepanov P, Bushman FD, Van Duyne GD (2012) Solution conformations of prototype foamy virus integrase and its stable synaptic complex with U5 viral DNA. Structure (London, England:1993) 20(11):1918-1928.

2017 – TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA