The Genetics of Health and Disease

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Illustration of person pulling down a segment of DNA

 

Our researchers have long been trailblazers in genetics and genomics, making the largest private-institution contribution to the Human Genome Project; discovering the first oncogene and the first tumor suppressor gene; and continuing to make major discoveries. They are advancing knowledge on how genetic instructions are decoded and carried out; how those processes go awry to cause conditions ranging from autism and Alzheimer’s to multiple sclerosis and cancer; and how female and male biologies “read” genomes differently, leading to significant differences in health and disease.

When Robert Weinberg discovered the first oncogene and the first tumor suppressor gene, the field of genetics was still in its infancy. Today, genetics is a key to research on most medical and developmental conditions. And gene-based approaches—such CRISPR gene editing—are increasingly central to studies on the cause and treatment of many diseases. But major questions remain about how our genome—our biological instruction manual—actually functions. Our researchers are pursuing answers and offering powerful new ways of thinking about how our genome works.

For example, David Page, who is already renowned for discoveries on sex chromosomes, is doing trailblazing work in the field of sex-based differences in biology: seeking to understand why some diseases affect more women than men (and vice versa) and why disease symptoms are often strikingly different according to sex. His ambitious program of research aims to define the molecular-level differences between sexes and explain how they contribute to health and disease. The work could change the practice of medicine, and it holds particular promise for improving health care for women.

Richard Young developed technology for mapping human genome regulatory circuitry and discovered the core regulatory circuitry of human embryonic stems cells. Today he is helping to pioneer the quickly developing field of phase-separated condensates, where cellular proteins form membrane-less droplets that may regulate gene expression. This new paradigm for how genes are transcribed offers a potentially powerful strategy for identifying therapeutic targets for cancer, Parkinson’s, and other diseases. Jonathan Weissman, who has created important tools for understanding how genetic instructions are translated into proteins, helped develop “CRISPR interference,” a method for precisely regulating gene expression that could underpin a new way to develop therapeutics. And Olivia Corradin is developing new ways to identify and assess the genetic risk factors and disease pathways associated with specific gene variants; a such study found, for example, that variants in the brain cells that produce myelin appear to contribute to multiple sclerosis, a fact which was previously unknown.

Learn more about our work on Genetics & Genomics—as well as related research in the realms of CancerInfectious Disease, Metabolism, Nervous System Development & Function, and Protein Form & Function.