Bert Vogelstein, MD, and Kenneth Kinzler, PhD, are codirectors of the Ludwig Center at the Sidney Kimmel Comprehensive Cancer Center of the Johns Hopkins University School of Medicine. Vogelstein and Kinzler demonstrated that colorectal cancer results from the sequential accumulation of mutations in oncogenes and tumor suppressor genes, establishing a paradigm for modern cancer genomics. Additionally, they discovered the tumor suppressors APC and TP53; they were the first to perform exomic sequencing in tumors; and they developed digital PCR. In an interview with JCI’s Editor-at-Large Ushma Neill, Vogelstein and Kinzler reflect on their career trajectories and past discoveries and discuss their goals as scientists.
Dr. Huda Zoghbi is a pediatric neurologist, a Howard Hughes Medical Institute investigator; a professor in the departments of Pediatrics, Molecular and Human Genetics, and Neurology and Neuroscience at Baylor College of Medicine; and the founding director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. Her work has focused on elucidating the mechanisms underlying Rett syndrome and spinocerebellar ataxia. In an interview with JCI Editor-at-Large Ushma Neill, Dr. Zoghbi describes her childhood in Beirut, Lebanon. After her medical studies were interrupted by Lebanon’s civil war, Dr. Zoghbi enrolled at Meharry Medical College. She became interested in pediatric neurological disorders during her residency, when she observed many patients with devastating disorders that appeared to have underlying genetic causes. Dr. Zoghbi also describes her discovery of a genetic cause of Rett syndrome, a null mutation in the methyl-CpG binding protein 2 (MeCP2), which researchers are now trying to target therapeutically.
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.