Scientific Initiatives / Genomic Medicine

The Need for a Genomic Medicine Initiative

The Salk Institute for Biological Studies received a $42 million gift—the largest in the Institute's history—to establish the Helmsley Center for Genomic Medicine (HCGM), a research center dedicated to decoding the common genetic factors underlying many complex chronic human diseases.

Broadly defined, genomic medicine is the science of using maps of human DNA—the genome—to understand how cells operate and generate new therapies for human disease. The Helmsley Center for Genomic Medicine (HCGM) will allow Salk researchers to use genomic data and powerful new technologies to decipher the molecular and genetic mechanisms that go awry in chronic disease.

The center will include scientists who are leaders in a range of biomedical research fields, including stem cell biology, endocrinology, cancer biology, metabolism, neurobiology, developmental biology, inflammation, and gene therapy. They will combine their efforts to understand how certain cellular pathways serve as lynchpins for chronic diseases such as cancer, diabetes and neurodegenerative disorders. Their findings suggest that developing therapies that address inflammation could help prevent and treat a broad range of disorders.

In addition to charting the common genomic basis for chronic conditions and uncovering new potential targets for therapies, the center's researchers will explore how genomic networks control stem cell development. This will allow researchers to manipulate genes to make stem cells useful for studying disease and regenerative medicine. The center will also explore how disease alters the epigenome, chemical switches on the DNA molecule that influence genetic activity, which may explain why patients with similar genetic profiles respond differently to treatment.

Genomic Medicine Initiative

Chronic diseases are painful, devastating and potentially fatal, and they represent billions of dollars in medical treatment costs. As the population of the United States ages, the costs to treat age-related epidemics like Alzheimer’s disease, diabetes and cancer are expected to climb into the trillions of dollars per year. At the same time, we are experiencing a biological renaissance driven primarily by new discoveries in genomics, epigenomics and regenerative medicine, and there are now real opportunities to develop novel treatments and therapeutics for chronic diseases at the molecular level.

Our understanding of all aspects of human health and disease, from genomics, stem cells, aging and personalized medicine to cancer, diabetes, inflammation and neurodegeneration, depends on a deeper knowledge of the genome and its products. Our genomes are dynamic in nature, responding in real time to environmental cues such as nutrient levels and circadian rhythms to influence neurotransmitters, growth factors and hormones throughout the body. The Salk Institute, through the Helmsley Center for Genomic Medicine, will revolutionize the life sciences and emerge as the leader in genomic medicine by defining how the human genome is regulated and altered during chronic illnesses, one of the fundamental challenges facing us now that the human genome has been sequenced. This undertaking requires knowledge of the regulatory code and the molecules and molecular activities that direct this complex process.

To deliver the next major breakthroughs in genomic medicine, the Salk Institute needs philanthropic support in four critical areas:

Five core research facilities will provide investigators with the resources and technical expertise to address the challenges laid out in the Genomic Medicine Initiative. Specifically, cores will provide investigators with the latest technology and state-of-the-art equipment, as well as highly skilled support staff, enabling them to effectively and efficiently perform experiments to ensure the maximal impact of this program on human health.

One of the founding principles of the Salk Institute has been to train the next generation of scientific leaders capable of thinking “outside the box.” The Helmsley Fellows program will build on this tradition by providing formalized postdoctoral training in genomic medicine research, producing the next generation of highly effective scientists.

The Helmsley Center for Genomic Medicine will recruit outstanding scientists working at the cutting-edge of genomic medicine, in areas such as metabolism, cancer, inflammation and stem cell research. These new faculty will integrate our existing areas of expertise and enhance our understanding of the links between chronic diseases.

The center will provide an extensive framework of scientific and technical services to facilitate the process of scientific discoveries that advance our understanding of human biology and lead to new therapeutic routes for the treatment of human diseases. This program provides an enhanced research environment to address the specific projects of the Helmsley Center for Genomic Medicine by offering expert consultations on a broad array of Institute-supported technologies to ensure that experiments are designed, executed and analyzed in optimal fashion.

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. Salk scientists will use genomic, metabolic, proteomic and pharmacologic approaches to understand how metabolic homeostasis is achieved and the impact of its dysregulation in chronic diseases.

Stem Cells
The stem cell program will conduct comprehensive studies aimed at discovering new approaches for the therapeutic treatment of chronic human diseases. These approaches will involve cell transplantation and/or the identification and development of compounds with therapeutic activities. Our approaches will take advantage of reprogramming technologies to generate transplantable human cell populations, as well as models of human diseases enabling newfound opportunities for the discovery of mechanisms of action, early interventions, and disease prevention. We will focus on the safety and potential clinical application of reprogramming and regenerative approaches, including induced pluripotent stem cell (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 Helmsley investigators at the Salk Institute, will contribute to bringing stem cell and regenerative therapies to the clinic.

Cancer Metabolism and Inflammation
The re-emergence of cancer metabolism as an important area of study stems in part from discoveries that a number of common oncogenes and tumor suppressor genes more directly control cell metabolism than previously thought. In addition, a number of metabolic enzymes are often mutated in a variety of human cancers. Ultimately, the hope is that detailed knowledge of oncogene and tumor suppressor gene functions and their effects on metabolism will lead to drug combinations that will be far more effective in treating cancers. Salk scientists will use genetic mouse models to decipher the roles of both metabolic dysregulation and inflammation in several of the deadliest cancers of man: glioblastoma, colorectal cancer, pancreatic cancer, and lung cancer.