Lead a small virology team working on preclinical in vitro studies of a host-targeting, broad-spectrum antiviral compound to meet FDA IND guidance. Work with academic collaborators and CROs to expand pan-viral profile of host-targeting modulators, including vendor evaluation, study design, MTA, SRA and data evaluation.Implement an highly specific HBV cccDNA inversion quantitative PCR (cinqPCR) to accurately evaluate compound antiviral activity against HBV cccDNA.

Negotiate and implement licensing of SARS-CoV-2 (COVID-19) systems that can be safely used in BSL-2 lab for antiviral discovery/development.Develop SARS-CoV-2 high throughput screening (HTS) platform and oversee screening of over 200,000 compounds leading to identification of novel classes of SARS-CoV-2 inhibitors.Lead mechanism of action (MOA) studies that combine classic virology techniques and next generation sequencing (NGS), leading to successful identification of novel viral targets.Work closely with medicinal chemistry group on structure-activity relationship (SAR) studies to optimize SARS-CoV-2 inhibitors, achieving a breakthrough of antiviral activity and improved stability.

Lead projects in preclinical development of self-amplifying mRNA (SAM) vaccines with broad applications in vaccination of viral infections, therapeutic intervention of allergy and virus-associated chronic diseases.Serve as a lead scientist in GSK Vaccines COVID-19 task force for developing rapid vaccine response to emerging virus outbreaks.Design, generate and in vitro characterize self-amplifying mRNA vaccines and investigate innate immune response (Molecular Therapy, 2022).Develop innovative RNA virus reverse genetics and nanoparticle technology platform. Implement innate immune reporter system and next-generation human in vitro tissue culture models for vaccine development.

Laboratory of Dr. Mary EstesHuman norovirus replication, innate immune response, and antiviral drug developmentHuman norovirus replication and innate immune response in a novel stem-cell-derived human intestinal enteroid culture system (Science, 2016; PNAS, 2020).Host Interferon response to human norovirus RNA replication in cultured mammalian cells (Journal of Virology, 2016).Development of NoroGLuc, a Gaussia luciferase-based human norovirus protease reporter system for the profiling of viral protease precursors and evaluation of inhibitors (Journal of Virology, 2014).

Laboratory of Dr. Stan Lemon Evasion of RIG-I/MDA5- and TLR3-dependent innate immunity by hepatitis A virus (HAV)HAV disruption of host RIG-I/MDA5 interferon signaling pathway through cleavage of signaling protein MAVS by the virus-encoded protease precursor 3ABC (PNAS, 2007).HAV inhibition of host TLR3-dependent interferon signaling pathway through cleavage of signaling protein TRIF by the viral protease-polymerase precursor 3CD (PLoS Pathogens, 2011).HAV and HCV: Similar induction and evasion of interferon responses, different disease outcomes (Seminar in Liver Diseases, 2010).

Antiviral development of small molecule inhibitors of hepatitis C virus (HCV).Develop cell-based and virus-based assays for screening of HCV nucleotide inhibitors.Conduct mechanism of action studies of lead HCV inhibitors by selection of drug-resistant mutant viruses and reverse genetics.Participate in IND submission for a nucleotide inhibitor of HCV that progressed to Phase II clinical trial.

Laboratory of Dr. Charlie RiceMolecular mechanism of bovine viral diarrhea virus (BVDV) cytopathic effectIsolation and characterization of non-cytopathic mutant viruses of BVDV: An unexpected role of viral nonstructural protein NS4B in viral cytopathic effect (Journal of Virology, 2001).The uncleaved BVDV nonstructural protein precursor NS2-NS3: A role in production of infectious virus particles (Journal of Virology, 2004).