UT Southwestern Breakthrough Prize Recipients:
Dr. Helen Hobbs // 2016
Lipid Metabolism and Fatty Liver Disease
Dr. Hobbs won the 2016 Breakthrough Prize in Life Sciences in recognition of transformative genetics research techniques she developed and used to identify key genes involved in lipid metabolism and fatty liver disease. In 2000, Dr. Hobbs co-launched the Dallas Heart Study, a multiethnic population-based study of several thousand individuals in Dallas County. While other genetics researchers were focused on finding common differences in the genome that contribute to particular traits, Dr. Hobbs and her colleague, Dr. Jonathan focused on rare genetic variants, believing that understanding these “exceptions” could more quickly lead to biomedical breakthroughs. Together, they showed that individuals with inactivating mutations in the PCSK9 gene have a markedly reduced incidence of heart disease, a discovery that led to the development by drug companies of a stunningly effective class of drugs for lowering LDL cholesterol. Using data from the Dallas Heart Study, the two also discovered that certain variants of two genes are both strongly associated with fat accumulation in the liver. Subsequently, it has been shown that the same sequence variations are also associated with liver inflammation, cirrhosis, and liver cancer. Dr. Hobbs’ rare-variant or low-variant approach is now emulated by researchers worldwide.
Dr. Zhijian “James” Chen // 2019
Immune System Defenses
Dr. Chen was selected to receive the 2019 Breakthrough Prize in Life Sciences for his achievements in explaining how DNA triggers immune and autoimmune responses from the interior of a cell through the discovery of the DNA-sensing enzyme cGAS. He discovered several molecular pathways that detect pathogens inside cells and trigger the body’s immune response. One enzyme, cGAS, detects invading or misplaced DNA and has been linked to cancer and autoimmune diseases. cGAS senses the presence of DNA outside the nucleus, which is a sign that cellular functions have gone awry, and recruits cGAMP, starting a cascade of signals that ends up triggering an immune response. Dr. Chen began his distinguished career by revealing the critical workings of the protein ubiquitin, which is fundamental to identifying proteins inside cells for destruction and recycling processes to keep cells functioning. He later revealed that ubiquitin also played a crucial role in another protein, which he called MAVS in honor of the Dallas Mavericks, that sits on the outer membrane of the mitochondria. MAVS proved crucial in immune defense against viruses like influenza and Ebola.