Influenza activated cell death: DAI if you want to live!

Abstract: Influenza A viruses (IAV) kill most of the cell types in which they replicate, both in cell culture and in infected lungs in vivo. We have recently discovered a mechanism of cell death that appears to account for almost all IAV-activated death in infected cells. This pathway is initiated when the protein DAI senses IAV genomic RNA and nucleates the kinase RIPK3. RIPK3 then activates parallel pathways of programmed necrosis (necroptosis), as well as apoptosis. Necroptosis downstream of RIPK3 relies on MLKL and apoptosis on FADD, such that deletion of DAI, RIPK3, or MLKL+FADD renders mice extraordinarily susceptible to respiratory IAV replication and lethality. In my talk, I will summarize these published findings, as well as present unpublished results outlining how DAI is activated by IAV, as well as how selectively targeting necroptosis may have therapeutic benefit in lethal IAV disease.

Biography: Dr. Balachandran obtained by B.S. In Chemistry from Angelo State University, San Angelo, Texas, USA, in 1995, and his Ph.D. in Immunology and Molecular Pathogenesis from Emory University, Atlanta, Georgia, USA, in 2001. Following a postdoc in the laboratory of Glen Barber at the University of Miami, He started by independent lab at the Fox Chase Cancer Center in 2007.  In 2014, he was promoted to Associate Professor with tenure. His laboratory is interested in mechanisms of cell death activated by innate-immune signaling pathways, and exploiting these pathways for the treatment of disease, whether infectious, inflammatory, or malignant.