James Allison of the MD Anderson Cancer Center has made key discoveries on the regulation of T cell activation and modulation, including identification and characterization of the T cell antigen receptor and the T cell coreceptors CD28 and cytotoxic T lymphocyte antigen-4 (CTLA-4). He was awarded the 2015 Lasker~DeBakey Clinical Medical Research Award in honor of his discovery and subsequent development of CTLA-4–targeted monoclonal antibody therapy to unleash the immune response to cancer. In an interview with JCI Editor at Large Ushma Neill, Allison discusses his decision to pursue a PhD instead of an MD and his early experiences in applying biochemical techniques to immunological questions. Additionally, Allison talks about the process of moving anti–CTLA-4 therapy into the clinic.
Oliver Smithies of the University of North Carolina at Chapel Hill was awarded the 2007 Nobel Prize in Physiology or Medicine for pioneering homologous recombination of transgenic DNA, which allowed for the creation of knockout and transgenic mice. Smithies’ lab created the first murine models of cystic fibrosis. He has also identified genetic factors involved in heart disease, atherosclerosis, and other disorders. In an interview with JCI Editor-at-large Ushma Neill, Dr. Smithies discusses his early interest in science, including his propensity for tinkering, the invention of starch gel electrophoresis, and his first molecular genetic studies of haptoglobin. Smithies also describes the three year development of his protocol for genetic transformation of human cells, his feelings on winning the Nobel Prize, and his admiration for Johann Sebastian Bach.
Helen Hobbs is an investigator of the Howard Hughes Medical Institute and a professor of Internal Medicine and Molecular Genetics at the University of Texas Southwestern Medical Center. Additionally, she is the director of the Dallas Heart Study, a longitudinal, multiethnic population-based study of over 6,000 adults that aims to identify genetic, protein, and imaging biomarkers for early detection of cardiovascular disease as well as social, behavioral, and environmental factors that contribute to cardiovascular disease risk. By studying outliers in this population, Dr. Hobbs identified a genetic defect in PCSK9 that is responsible for low plasma LDL levels. In an interview with JCI Editor-at-Large Ushma Neill, Dr. Hobbs discusses her early scientific training at Parkland Memorial Hospital in Dallas under the direction of Donald Seldin, who guided her to scientific bench training. She also discusses the initiation of the Dallas Heart Study and the development of a therapeutic inhibitor of PCSK9 for lowering LDL.
Editor-at-Large Ushma Neill interviews Rudolf Jaenisch of MIT’s Whitehead Institute. Dr. Jaenisch created the first transgenic mice and conducted the first experiment demonstrating that therapeutic cloning could correct a genetic defect. Additionally, Jaenisch has been at the forefront of research on induced pluripotent stem cells and has shown that these cells can correct sickle cell anemia and Parkinson disease in rodents. In this interview, Jaenisch discusses his work as a postdoctoral fellow in Arnold Levine’s lab studying DNA replication with the tumor virus SV40, which led to his collaboration with developmental geneticist Beatrice Mintz. Additionally, Jaenisch discusses adoption of new methods and technologies to address interesting questions in genetics as well as the application of these technologies to humans.
Dr. Stuart Kornfeld is the David C. and Betty Farrell Distinguished Professor of Medicine at Washington University in St. Louis. He is best known for his work elucidating the processes governing lysosome biogenesis. His research continues to uncover roles for oligosaccharide biosynthesis, processing, and maturation in mediating proper folding and transport of proteins. In an interview with JCI Editor-at-Large Ushma Neill, Kornfeld discusses how his first biochemistry course, taught by Carl and Gerty Cori, and his work as a postdoctoral researcher in Luis Glaser’s lab led to his interest in the role of sugar moieties in cellular physiology. Kornfeld also discusses his early work with postdoctoral fellows Ira Tabas and Ajit Varki and graduate student Marc Reitman in characterizing the trafficking of lysosomal proteins. Finally, Kornfeld addresses the importance of mentors in the development of physician-scientists.