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Vaithilingaraja Arumugaswami, MVSc., PhD.
Director, Viral Vector Core Facility, Regenerative Medicine Institute
|Regenerative Medicine Institute|
|Assistant Professor, Surgery|
Understanding the molecular mechanisms of cancer-causing Hepatitis C Virus (HCV) replication and developing a human pluripotent stem cell based ex-vivo gene therapy strategy for regenerating hepatitis C damaged liver. The lab also focuses on disease modeling HCV and HIV pathogen-host interactions using human induced pluripotent stem cell (iPSC)-derived primary cells.
Developed a high-throughput functional profiling system for viral pathogens using next generation sequencing platform.
Current investigations include:
Translational: The focus of the lab is to develop a stem cell based therapy for regenerating Hepatitis C damaged liver. This effort includes, developing a genetic circuitry based on pathogen induced therapeutic gene expression system in patient-specific iPSC lines. These cell lines are engineered with therapeutic cassette 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. Besides, our group focuses on developing strategies for whole liver organ engineering utilizing natural liver scaffolds and micro-fluidic bioreactors.
Basic: This effort involves the systematic characterization of cis-acting replication elements (CRE) in the protein encoding region of HCV genome. Viral genomic RNA sequences, coding for polypeptide, form secondary and tertiary structures, which can play 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.
- Khachatoorian R, Arumugaswami V, Ruchala P, Raychaudhuri S, Maloney EM, Miao E, Dasgupta A, French SW: A cell-permeable hairpin peptide inhibits hepatitis C viral nonstructural protein 5A-mediated translation and virus production. Hepatology, 55(6): 1662-72, 2012
- Gonzalez O, Fontanes V, Raychaudhuri S, Loo R, Loo J, Arumugaswami V, Sun R, Dasgupta A, French SW: The heat shock protein inhibitor Quercetin attenuates hepatitis C virus production. Hepatology, 50(6): 1756-64, 2009
- Arumugaswami V, Sitapara R, Hwang S, Song MJ, Ho TN, Su NQ, Sue EY, Kanagavel V, Xing F, Zhang X, Zhao M, Deng H, Wu TT, Kanagavel S, Zhang L, Dandekar S, Papp J, Sun R: High-resolution functional profiling of a gammaherpesvirus RTA locus in the context of the viral genome. J. Virol., 83(4): 1811-22, 2008
- Arumugaswami V, Remenyi R, Kanagavel V, Sue EY, Ngoc Ho T, Liu C, Fontanes V, Dasgupta A, Sun R: High-resolution functional profiling of hepatitis C virus genome. PLoS Pathog., 4(10): e1000182, 2008
- Sanchez DJ, Miranda Jr, Arumugaswami V, Hwang S, Singer AE, Senaati A, Shahangian A, Song MJ, Sun R, Cheng G: A repetitive region of gammaherpesvirus genomic DNA is a ligand for induction of type I interferon. J. Virol., 82(5): 2208-17, 2007
- Arumugaswami V, Wu TT, Martinez-Guzman D, Jia Q, Deng H, Reyes N, Sun R: ORF18 is a transfactor that is essential for late gene transcription of a gammaherpesvirus. J. Virol., 80(19): 9730-40, 2006