Jonathan Barasch, MD PhD


Barasch

Jonathan Barasch MD PhD is a Professor of Medicine, Pathology and Cell Biology. He has been studying the trafficking of iron in kidney development, kidney ischemic damage, and kidney infections.

Dr. Barasch’s lab discovered a switch in iron utilization during late gestation, a receptor for ferritin called Scara5 (Developmental Cell, 2009), a new transmembrane conductance (Unpublished), and with Roland Strong (FHCRC) a siderophore/iron chelator called Siderocalin or Ngal (Molecular CelI, Lancet, Nature Chemical Biology, Nature Medicine).

The mechanisms of iron transport by Siderocalin-Ngal has been a major focus resulting in the identification of a mammalian siderophore (Nature Chemical Biology), an iron chelator therapeutic (a mutant form of Ngal; Unpublished), and a biomarker of tubular damage distinct from volume depletion (Letter to NEJM, Journal Clin Invest, Annals of Internal Medicine, JASN, JACC) now approved for clinical use.

These studies pointed to an unexpected finding, the α-intercalated cell was the critical cellular source of Siderocalin-Ngal. In fact, LPS and Bacteria bound directly to these cells, initiating a cascade that included expression of Siderocalin-Ngal and a myriad of inflammatory cytokines, as well as urinary acidification. Deletion of either Siderocalin-Ngal or the intercalated cells themselves by the deletion of the new transcription factor discovered by Barasch, prolonged bacterial colonization. These data cast a new light on iron trafficking and iron chelation by the kidney as a coordinate program of antimicrobial defense centered on intercalated cells which we propose are new members of the innate immune pathway. Further, we propose that dysfunction of the intercalated cell is a common phenomenon in reflux and obstructive uropathy accounting for changes in urine composition and urine infection.

Dr. Barasch’s current work is focused on modeling iron traffic in kidney damage and kidney infection and on identifying the full functions of intercalated cells. In addition to research, Dr. Barasch sees renal damage patients and teaches molecular sciences at Columbia Physicians and Surgeons, New York.