B2-049A CHS

Research Description:

My laboratory focuses on understanding the pathogenic mechanisms of Flaviviridae family of viruses – Hepatitis C Virus, Zika Virus and Dengue Virus. Globally over 3 billion people are at risk of contracting these viral pathogens through mosquito vectors and contact with contaminated blood and bodily fluids. Zika virus (ZIKV), a major human pathogen, causes congenital eye disease and microcephaly. ZIKV is transmitted by Aedes species of mosquitoes and through sex. Currently, there is no vaccine or treatment available against ZIKV. Our main research focus is to develop a potent recombinant vaccine to prevent Zika virus infection. We have developed a reverse genetics system to engineer attenuating mutations in the Zika viral genome and animal models to test the safety and immunological profiles of these engineered vaccine candidates. In addition, we are investigating the differing impact of sexual (vaginal and rectal routes) and mosquito vector modes of transmission in infected adults on fetal outcome. For modeling congenital ZIKV eye disease, we are utilizing human pluripotent stem cells derived ocular progenitor cells and 3D optic cup organoids. In these human cell-based systems, we have observed differential activation of signaling pathways and long non-codling RNAs (lncRNAs) by various Zika viral pathotypes. We are evaluating the genetic and molecular basis of these specific cellular perturbations, which can allow for understanding the basic biology of eye development and identifying novel therapeutic interventions. We are further focusing on developing a recombinant Zika virus-based immuno-oncolytic therapy targeting glioblastoma (GB). Cancer immuno-therapies have been shown to be effective for hematologic cancers, but demonstrate limited efficacy for solid tumors. We propose that oncolytic virus based solid tumor cell killing can provide space and additional stimuli to recruit host T-cells as well as CAR-T cells to cancer site. Despite decades of research, patients with glioblastoma have a median survival of 12 to 15 months following diagnosis. Zika virus-based oncolytic therapy can provide additional treatment option to this destructive cancer.

Member: CTSI

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