Gaya K. Amarasinghe, Ph.D.

Professor
Pathology and Immunology
Laboratory and Genomic Medicine
Biochemistry and Molecular Biophysics
Molecular Microbiology

Immunology Program
Biochemistry, Biophysics, and Structural Biology Program
Molecular Microbiology and Microbial Pathogenesis Program

  • (314) 286-0619

  • 314-286-0690

  • 8118

  • 7752A CSRB

  • gamarasinghe@WUSTL.EDU

  • https://sites.wustl.edu/amarasinghelab/

  • interferon, viral infection, structural biology, signaling, biochemistry

  • Signaling through interferons: Mechanisms and implications for viral pathogenesis and cancer biology

Research Abstract:

The overarching goal of my research program is to develop a mechanistic understanding of host-pathogen interactions with biological consequences to pathogenesis. These interactions promote host immune suppression and enhance pathogen replication in cell and tissue specific manner, but remain incompletely described. Results from these studies will inform on molecular mechanisms of action during infection as well as insights into potential therapeutic targets and mechanisms of action. We currently use biochemical and biophysical methods to identify and characterize components from hosts and pathogens in order to develop an atomic resolution framework. Importantly, these efforts also provide opportunities to mentor a range of trainees, including undergraduates, graduate students and postdoctoral fellows.

Selected Publications:

Leung DW,
Ginder ND, Fulton DB, Nix J, Basler CF, Honzatko RB, Amarasinghe GK. Structure of the Ebola VP35 interferon inhibitory
domain. Proc Natl Acad Sci 2009; 106(2):411-416. PMCID: PMC2626716



Leung DW, Prins K,
Borek DM, Farahbakhsh M, Tufariello JM, Ramanan P, Nix JC, Helgeson LA,
Otwinowski Z, Honzatko RB, Basler CF, Amarasinghe
GK
:  Structural basis for dsRNA
recognition and interferon antagonism by Ebola VP35.  Nat
Struct Mol Biol 2010;17:165-172.  PMCID: PMC2872155



Binning JM, Wang T, Luthra P, Shabman RS, Borek DM, Liu G,
Xu W, Leung DW, Basler CF, Amarasinghe GK. Development of RNA aptamers
targeting Ebola virus VP35. Biochemistry 2013; 52(47):8406-8419. PMCID:
PMC3909728



Hyde JL, Gardner CL, Kimura T, White JP, Liu G, Trobaugh DW,
Huang C, Tonelli M, Paessler S, Takeda K, Klimstra WB, Amarasinghe GK, Diamond MS. A viral RNA structural element alters
host recognition of non-self RNA. Science
2014; 343(6172):783-787. PMCID: PMC4209899



Brown CS, Lee MS, Leung DW, Wang T, Xu W, Luthra P, Shabman
RS, Melito LM, Millan KS, Borek DM, Otwinowski Z, Ramanana P, Stubbs AJ,
Peterson DS, Binning JM, Olson MS,  Ready
JM, Basler CF, Amarasinghe GK. In
silico derived small molecules bind the filovirus VP35 protein and inhibit its
polymerase co-factor activity. J Mol Biol 2014; 426(10):2045-2058. PMCID:
PMC4163021

Leung DW, Borek D, Luthra P, Binning JM, Anantpadma M, Liu G,
Harvey IB, Su Z, Endlich-Frazier A, Pan J, Shabman RS, Chiu W, Davey RA,
Otwinowski Z, Basler CF, Amarasinghe GK.
An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA
Synthesis by Modulating Nucleoprotein-RNA Interactions. Cell Rep 2015; 11(3):376-389.  PMCID: PMC4599368

Xu W, Luthra P, Wu C, Batra J Leung DW, Basler CF, Amarasinghe GK. Ebola virus VP30 and
nucleoprotein interactions modulate viral RNA synthesis. Nat Commun 2017;
8:15576. PMCID: PMC5472179



Chatterjee S, Luthra P, Esaulova E, Agapov E, Yen BC, Borek
DM, Edwards MR, Mittal A, Jordan DS, Ramanan P, Moore ML, Pappu RV, Holtzman
MJ, Artyomov,M, Basler CF, Amarasinghe
GK,
Leung DW. Structural basis for human respiratory syncytial virus
NS1-mediated modulation of host responses. Nat Microbiol 2017; 2:17101. PMCID:
PMC5739881



Xu W, Luthra P, Wu C, Batra J, Leung DW, Basler DW, Amarasinghe GK. Ebola virus VP30 and
nucleoprotein interactions modulate viral RNA synthesis. Nat Commun 2017; 8:15576.
PMCID: PMC5472179



Su Z, Wu C, Shi L, Luthra P, Pintilie GD, Johnson B, Porter
JR, Ge P, Chen M, Liu G, Frederick TE, Binning JM, Bowman GR, Zhou ZH, Basler
CF, Gross ML, Leung DW, Chiu W, Amarasinghe
GK
. Electron cryo-microscopy structure of Ebola virus nucleoprotein reveals
a mechanism for nucleocapsid-like assembly. Cell 2018; 172(5):966-978. PMCID:
PMC5973842

Johnson B, VanBlargan LA, Xu W, White JP, Shan
C, Shi PY, Zhang R, Adhikari J, Gross ML, Diamond MS, Amarasinghe GK. Human IFIT3 modulates IFIT1 RNA binding specificity
and protein stability. Immunity 2018; 48(3):487-499. PMCID: PMC6251713

Last Updated: 5/26/2021 11:28:56 AM

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