My research interest focuses on the molecular action of ribosome inactivating proteins (RIPs), including ricin and Shiga toxins. Ricin is one of the most toxic substances in nature. It can be easily extracted from the seeds of Ricinus communis or from the byproduct of castor oil, which are processed worldwide on an industrial scale. The Shiga toxin-producing Escherichia coli infections are associated with severe gastrointestinal disease in humans and are responsible for significant morbidity and mortality world-wide. There are no vaccines or therapeutics against ricin or Shiga toxin. Using Saccharomyces cerevisiae as a model system, combing the molecular, genetic, biochemical, and biophysical methods I examine the catalytic activity of ricin and Shiga toxins and their relation with the ribosome interaction. I have showed that ricin A chain (RTA) using ribosomal P protein stalk to access its target, the α-sarcin/ricin loop (SRL) of the large rRNA. On RTA, the ribosome binding side and the active site are located on the opposite surfaces of the protein. We also found both Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2) interact with ribosomal P protein stalk to depurinate ribosome. But Stx2 interact with ribosome much better than Stx1 and the A1 subunit of Stx2 has higher catalytic activity than the A1 subunit of Stx1. Our current working model for RTA and Shiga toxins is that the active subunits of both toxins use the sides that is opposite to their active sites to interact with the ribosomal P protein stalk. By a conformational change, the P protein stalk delivers the toxin to SRL in the right orientation to stimulate the depurination reaction. My current research focuses on understanding the structural features of RTA and Stxs critical for their interaction with ribosomes to develop mechanistic approaches to control toxin-mediated disease. The long term goal of my research is to develop effective antidotes based on understanding of the mechanism of action of ricin and Shiga toxins.
I am also in charge of the Biacore instrument in the SEBS Core Facility (http://sebs.rutgers.edu/core-facility/) and providing assistants of using Biacore to measure the kinetic interaction of molecules.
Title and Address:
Associate Research Scientist
Department of Plant Biology
School of Environmental and Biological Sciences,
Rutgers, The State University of New Jersey
Primary Focus Area: The mechanisms of cellular toxicity of ricin and Shiga toxins
Secondary Focus Area: Fragment based antidotes development against ricin and Shiga toxins