The programmed cell death network is comprised of several inter-connected pathways, including apoptosis, programmed necrosis and autophagy.
We wish to understand how non-canonical protein translation regulates cell fate decisions involving cell death and differentiation, specifically by studying the cap-independent translation factor DAP5.
We have conducted extensive structure-function and mechanistic analysis to map specific nodes within the PCD network. Here, as an example, we provide our annotation of the DAPK family of protein kinases.
We have generated PCD-specific platforms that monitor protein-protein interactions in cells to discover novel interactions among the PCD proteins. We are applying whole genome siRNA screens to uncover novel pathways mediating inter-modular cross-talk and alternative death pathways. The physiological implications of the various mechanisms are being investigated in early embryonic differentiation.
We have applied our new insights into the PCD network to understand cancer progression, response to standard treatment, and to develop precision therapy based on the integrity of the PCD network and its composite nodes in individual tumors.