The genomic revolution is upon us, transforming basic biological research and the entire field of health care. The Helmsley Center for Genomic Medicine (HCGM) at the Salk Institute for Biological Studies in partnership with The Helmsley Charitable Trust was created to further our understanding of the deep genetic connections shared by chronic diseases. Although chronic illnesses manifest themselves in very different ways, they share similar genetic properties, suggesting closely related underlying biological processes. If we can understand the similarities between chronic illnesses at the genomic level, we can fundamentally transform the ways we study and treat these diseases. Knowledge of these key common activators will provide the framework for the development of novel therapies and regenerative tools to treat disease at the molecular level.
The Salk Institute was established to explore questions about the basic principles of life, with the goal of providing a collaborative environment that encouraged researchers to consider the wider implications of their discoveries for the future of humanity. We believe that we are at the cusp of a revolution in understanding the fine details of chronic disease and defining a new approach, a genomic approach, to its treatment. A common conviction that inflammation might be the underlying cause of many chronic diseases brought together a group of scientists with overlapping interests to tackle this problem. These researchers come from different disciplines and have different areas of expertise and different ways of looking at the problem, but they all realized that if they pooled their intellectual resources, they could collectively dissect the molecular underpinnings of this tough biological problem. It has become apparent that common genetic and metabolic pathways operate in disparate diseases such as cancer, neurological diseases and diabetes. For example, the dedifferentiation and reprogramming principles that are used to generate pluripotent stem cells are the hallmarks of many deadly cancers. To deconstruct these common genetic and metabolic pathways, Salk scientists have to identify genes, perform genetic analysis, decode the genomic changes, and unravel the epigenome, proteome and metabolome.
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.
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.