Research Areas

Translational

We are focused on developing a stem cell-based therapy for regenerating hepatitis C damaged liver. HCV is a major world health issue infecting over 170 million individuals. The infection becomes chronic in approximately 80% of cases, with grave medical consequences. Most will develop cirrhosis of the liver and/or liver cancer as a consequence. Currently there is no vaccine available for preventing HCV infection. HCV is the leading indicator of liver transplants, and 29% of transplants performed are due to hep C. Liver transplantation ranks second in frequency (after kidney) among major organ transplantation in the Unites States. Recurrence of HCV in newly transplanted liver is a grave concern and often requires repeated liver transplantation. Shortage of liver donors, limited treatment response rate and recurring HCV infection warrant the development of novel therapeutic strategies. Utilizing autologous hepatocytes, rendered resistant to HCV, for repopulating the HCV infected/decompensated liver is a promising therapeutic option. Our research effort includes developing a genetic circuitry based on pathogen-induced therapeutic gene expression systems in patient-specific iPSC lines. These cell lines are engineered with HCV therapeutic cassettes using zinc-finger nucleases and TALENs. The engineered stem cells are subjected to derivation of functional liver lineage cells for HCV infection studies. A humanized mouse model is used for investigating engraftment efficiency of the engineered hepatic lineage cells. In addition, our group focuses on developing strategies for whole-liver organ engineering utilizing natural liver scaffolds and micro-fluidic bioreactors.

Humanized mouse model for liver engraftment study. The mice were xenografted with luciferase-labeled human pluripotent stem cell-derived liver progenitors. One week post-engraftment the animals were imaged using Xenogen In Vivo Imaging System.

 

Basic

This effort involves the systematic characterization of cis-acting replication elements (CRE) in the protein encoding region of the HCV genome. Viral genomic RNA sequences, coding for polypeptide, form secondary and tertiary structures, which can play a critical role in viral genome replication and genome packaging. We have generated a library of mutant viruses having silent mutations that are being evaluated in cell culture and in vivo conditions. Understanding the structural and functional aspects of CRE can provide better insights for designing vaccine candidates and developing additional therapeutic strategies.

Android app on Google Play