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.
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,
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GK: Structural basis for dsRNA
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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