Videos
The pulmonary disease tuberculosis (TB) is a global health problem that results from Mycobacterium tuberculosis (Mtb) infection. As parasitic helminth worms are endemic to areas with high rates of TB, helminths are thought to enhance susceptibility to Mtb. In this episode, Shabaana Khader and colleagues demonstrate that helminth coinfection exacerbates TB by promoting formation of arginase-1-expressing inflammatory granulomas, resulting in increased lung damage. Moreover, inflammatory phenotypes associated with coinfection were reversed in a murine co-infection model by treatment with anti-helminthic agents. This study provides mechanistic insight into the link between helminth coinfection and TB disease severity.
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.
Granulomatosis with polyangiitis (GPA) is a form of autoimmune vasculitis that is associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCAs) directed against proteinase 3 (PR3). In this episode, Véronique Witko-Sarsat, Nathalie Thieblemont, and Katherine Martin discuss their work, which shows that PR3 expression is enhanced on the surface of apoptotic neutrophils from GPA patients. PR3-expressing apoptotic neutrophils were found to promote pro-inflammatory responses and prevent the development of regulatory T cells. Moreover, the authors show that this immune dysregulation was also present in GPA patients. Together, the results of this study provide important insight into the pathogenesis of GPA.
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.
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