The goal is to determine the roles of metabolic dysregulation and inflammation in the initiation and progression of human cancers, including glioblastoma, colorectal, lung, pancreatic, and prostate cancers. We will test our underlying hypothesis that inflammatory and metabolic cues are regulated by therapeutically accessible signaling pathways in genetic mouse models, as well as in biopsied tissues from human tumors. These studies will involve not only the expertise of the Shaw (cancer metabolism) and Verma (cancer and inflammation) labs, but also will incorporate research from the Evans, Montminy, Gage, and Belmonte laboratories.
Diabetes and Metabolism
Metabolism is arguably not only the most fundamental of biological processes but also the most complex. For the multicellular organism, metabolism must be constantly controlled and tightly communicated across a wide variety of tissues and organs. It must respond to dramatically fluctuating environmental conditions. In its dysfunction, even small imbalances between energetic intake and expenditure can cumulatively result in drastic perturbations, which in turn influence organismal health. It is not surprising, then, that a large and complex network of genetic switches composed of hormones and receptors has evolved to monitor and signal metabolic changes across the organism, and that the appropriate activation of this metabolic network has proven critical for survival. We will use genomic, metabolic, proteomic and pharmacologic approaches to understand how metabolic homeostasis is achieved and the impact of its dysregulation in chronic diseases.
The overall goal is to discover new therapeutic treatments for chronic human diseases involving cell transplantation and/or the identification and development of compounds with therapeutic activities. Our approaches will leverage reprogramming technologies to generate transplantable human cell populations, as well as novel models of human diseases crucial in deciphering the mechanisms of disease pathology and evaluating early intervention and disease prevention options. We will focus on the safety and potential clinical application of reprogramming and regenerative approaches involving iPSC generation and differentiation, lineage conversion, mobilization of endogenous progenitor cells, application of adult stem cells, and in vivo reprogramming leading to endogenous regeneration. We believe that these approaches, alongside the targeted gene-editing technologies based on homologous recombination developed by the HCGM Investigators at the Salk Institute, will aid the progression of stem cell and regenerative therapies to the clinic.