Videos
Damage to the glomerulus, which mediates the kidney's filtering function, causes plasma protein to spill into the urine, a sign of kidney failure and cardiovascular disease. Calcium influx into the podocytes, the cells that form the filtration barrier of the glomerulus, is known to damage the glomerulus, but the ion channel that mediates this influx was unknown. In this episode, Anna Greka and colleagues discuss their recent work demonstrating that inhibition of the TRPC5 ion channel protects mice from kidney damage by preventing calcium influx into the podocytes, and blocks the cytoskeletal alterations in the podocytes that disrupts the filtration barrier in the glomerulus.
Results from early-phase clinical trials have indicated that recombinant adeno-associated viruses (rAAV) could potentially be used for gene therapy. In each trial, however, patients have developed T cell-mediated immune responses that may interfere with therapeutic gene expression. In this episode, Terence Flotte and Christian Mueller discuss their recent study investigating T cell responses to intramuscular injection of a rAAV encoding M-type a1-antitrypsin (AAT) in patients with AAT-deficiency. Their results demonstrate that AAT expression persists for up to 12 months and suggest that immunomodulation of T cell populations may not be necessary for long-term, rAAV-mediated transgene expression.
Much of our current understanding of calcium metabolism rests in large part on a series of discoveries made by John T. Potts Jr. of the Massachusetts General Hospital. Potts is an internationally recognized authority on calcium metabolism and parathyroid hormone (PTH) in particular. In addition to his research, he carried an enormous leadership role, serving as both Chairman of Medicine and Physician in Chief of the MGH between 1981 and 1996. Watch the full interview for stories about working with Berson and Yalow, his approach to leading the MGH, and what has changed over his 56 years there.
In order to mount an effective immune response, T cells must be primed with the appropriate antigens to help them recognize malignant or pathogen-infected cells. Tim Greten and colleagues examined how necrotic cell death influences T cell cross-priming. Here they report on a molecular mechanism that blocks antigen cross-presentation by necrotic cells. Moreover, they found that this mechanism could be circumvented to promote immunogenicity of tumor cells.
For decades, the attention of the scientific community was focused on the central dogma of biology — the decoding of the genetic information embedded in DNA. Little research was dedicated to how proteins are degraded and removed from cells. Enter onto the scene a young graduate student, Aaron Ciechanover, who with his mentor Avram Hershko, uncovered the complex and elegant ubiquitin proteolytic system. For his discovery, Dr. Ciechanover shared in the 2004 Nobel Prize in Chemistry with Hershko and Irwin Rose. Watch the complete interview for more stories about being a member of the Pontifical Academy of Sciences, the magic of “A-ha” moments, and the conflict between religion and Darwinism.
Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)