The Balachandran lab is interested in how cells die during host innate-immune responses to viruses and bacteria, and in exploiting these mechanisms for the treatment of human disease, whether infectious, inflammatory or malignant.  In particular, the lab is interested in a form of programmed cell death termed necroptosis, driven by the kinase RIPK3. Unlike apoptosis, which proceeds via a caspase cascade that results in the ordered disassembly of the cell, necroptosis is caspase independent and driven by the RIPK3 substrate MLKL. Once activated by RIPK3, MLKL translocates to cellular membranes and induces their disruption, resulting in a form of necrotic cell death. Necroptosis is activated by several classes of innate-immune receptor (e.g., TLRs and cytokines such as TNF-α and interferons) and pathogen (e.g., RNA viruses, DNA viruses, certain gram-negative bacteria). The Balachandran lab is interested in how viruses (particularly RNA viruses), gram-negative bacteria, cytokines, and cellular stresses activate the necroptosis machinery, how necroptosis functions during acute viral and microbial infections to control pathogen spread, and how this death modality can be leveraged for immunotherapy.