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 Cohen 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.
Dr. Masashi Yanagisawa // 2023
Dr. Yanagisawa received the 2023 Breakthrough Prize in Life Sciences for his discovery of the cause of narcolepsy in work that has led to new treatments for this condition that results in dangerous daytime sleepiness. Dr. Yanagisawa was honored along with Emmanuel Mignot, M.D., Ph.D., of Stanford University, who made the same discovery independently. Drs. Yanagisawa and Mignot showed that central to the disease of narcolepsy is the protein orexin, which ordinarily regulates wakefulness. In some animals, such as dogs, narcolepsy is caused by a mutation affecting the neural receptor to which orexin binds; but in humans, the disease is triggered by the immune system attacking the cells that produce orexin – probably “mistaking” it for a viral particle. Drs. Yanagisawa and Mignot’s discoveries have led to treatments shown to relieve the symptoms of narcolepsy, as well as to the design of sleep-inducing drugs. Dr. Yanagisawa discovered orexin in 1998. More than a decade ago, he launched an ambitious two-continent, large-scale forward genetics program to screen for sleep/wake abnormalities in mice. That ongoing project has led to the identification of several new genes considered of great importance in the regulation of sleep.