Pei-Yong Shi, PhD
I. H. Kempner Professor of Human Genetics
Professor, Department of Biochemistry & Molecular Biology
Tel: (409) 772-6370
Fax: (409) 742-4298
E-mail:
peshi@utmb.edu Campus Location:5.138B T.G. Blocker Medical Research Bldg
Mail Route: 1055
Research
The Shi lab integrates both academic and industrial
expertise for basic and translational research. Our research focuses on
flaviviruses that cause significant human diseases, such as dengue,
West Nile, and Japanese encephalitis viruses. Despite their global
public health burden, there is no clinically approved therapy for
flavivirus infection. To address this huge unmet medical need, we take a
multidisciplinary approach (i) to study the molecular mechanism of
viral replication and (ii) to translate the knowledge into
antiviral/vaccine products. Many of our projects are highly
collaborative with both academic and pharmaceutical partners around the
world. We also aspire to apply the knowledge achieved from the
flavivirus research to drug discovery and vaccine development for other
viral pathogens.
- Flavivirus replication
Understanding viral replication at a molecular level is essential
for development of novel intervention. Our basic research is designed
to decipher how viral and cellular factors modulate each other during
viral infection, leading to productive viral replication and effective
immune response. Our experimental approach includes biochemistry,
structural biology, chemical biology, molecular biology, and disease
modeling in vivo. The goal of these studies is to define the mechanisms
of viral replication and host response that could be used for
therapeutics and vaccine development. Progressing at the forefront of
basic research provides a competitive edge for our translational
research. In return, the translational research poses new questions and
provides unique tools (such as inhibitors) for the viral replication
research. - Antiviral development
Four strategies have been pursued to identify flavivirus
inhibitors: (i) High-throughput screening (HTS) using viral infection
assays; (ii) HTS using viral enzyme assays; (iii) structure-based in
silico docking and rational design; (iv) repurposing clinical compounds
(that have been previously developed for other indications) for
potential treatment of flavivirus infection. New insights derived from
viral replication research (described above) have enabled us to design
new inhibitors of viral proteins or inhibitors of host factors that are
essential for viral infection. Through collaboration with medicinal
chemists and pharmacologists, we advance these inhibitors towards
preclinical and clinical development. - Vaccine development
We discovered and invented a novel vaccine approach using mutant viruses defective in 2’-O
methylation of viral RNA. Viruses that replicate in the cytoplasm
cannot access the host nuclear capping machinery. These viruses have
evolved viral methyltransferase(s) to methylate N-7 and 2’-O cap of their RNA; alternatively, they ‘snatch’ host mRNA cap to form the 5’-end of viral RNA. The function of 2’-O
methylation of viral RNA cap is to mimic cellular mRNA and to evade
host innate immune restriction. A cytoplasmic virus defective in 2’-O methylation is replicative; but its viral RNA lacks 2’-O
methylation, and is recognized and subsequently eliminated by host
immune response. We are applying this novel vaccine approach to
flaviviruses.
Publications