Jaisri Lingappa received her BA from Swarthmore College, MD from the University of Massachusetts, and Ph.D. from Harvard University. She did an internship and residency in Internal Medicine and fellowship in Infectious Disease at the University of California at San Francisco (UCSF), followed by a postdoctoral fellowship at UCSF. Dr. Lingappa has been at the University of Washington since 1999 and is currently a Professor in the Dept. of Global Health, with an adjunct appointment in the Dept. of Medicine and the Dept. of Microbiology. As a postdoc, she began studying how viruses hijack host machinery during capsid assembly. Over the years, her research has helped to shift the field away from viewing virus assembly as a “spontaneous” process and towards viewing assembly as requiring “host-catalyzed” events in cells. Studies by her lab have shown that the HIV-1 capsid protein Gag is recruited into a cellular complex called the precursor RNA granule, which is where HIV-1 capsid assembly and genomic RNA packaging take place. They have also identified two cellular enzymes that act catalytically to facilitate HIV-1 assembly in cells: the ATPase ABCE1 and the RNA helicase DDX6 (RCK/p54). Their most recent studies show that the highly conserved ABCE1 protein binds to a highly conserved binding site in Gag. One current direction in the lab involves understanding how retroviral Gag proteins have evolved multiple ABCE1 binding sites. A second direction addresses how cellular proteins facilitate packaging of the HIV-1 genome during retrovirus assembly. A third direction involves investigating how polymorphisms that arise in Gag in vivo can enhance ABCE1-Gag binding, thereby accelerating the kinetics of this assembly pathway and increasing virus particle production. The latter studies have important implications for viral pathogenesis, since they test the hypothesis that altering viral-host interactions during assembly could impact viral set point and viral load. The Lingappa lab’s studies have also led to development of novel antiviral compounds that inhibit replication of various viruses - including rabies virus - by acting on ABCE1-containing assembly intermediates.
Recent Publications from PubMed
- Mutations of Conserved Residues in the Major Homology Region Arrest Assembling HIV-1 Gag as a Membrane-Targeted Intermediate Containing Genomic RNA and Cellular Proteins.Tanaka M, Robinson BA, Chutiraka K, Geary CD, Reed JC, Lingappa JRJournal of virology. 2015 Dec; 90 4: 1944-63
- Lingappa JR, Reed JC, Tanaka M, Chutiraka K, Robinson BAVirus research. 2014 Nov; 193 : 89-107
- A temporospatial map that defines specific steps at which critical surfaces in the Gag MA and CA domains act during immature HIV-1 capsid assembly in cells.Robinson BA, Reed JC, Geary CD, Swain JV, Lingappa JRJournal of virology. 2014 May; 88 10: 5718-41
- Lingappa UF, Wu X, Macieik A, Yu SF, Atuegbu A, Corpuz M, Francis J, Nichols C, Calayag A, Shi H, Ellison JA, Harrell EK, Asundi V, Lingappa JR, Prasad MD, Lipkin WI, Dey D, Hurt CR, Lingappa VR, Hansen WJ, Rupprecht CEProceedings of the National Academy of Sciences of the United States of America. 2013 Mar; 110 10: E861-8
- Reed JC, Molter B, Geary CD, McNevin J, McElrath J, Giri S, Klein KC, Lingappa JRThe Journal of cell biology. 2012 Aug; 198 3: 439-56