The Discovery of the Iron-Regulatory Hormone Hepcidin.

Abstract

Featured Article: Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001;276:7806–10.2 Louis Pasteur's adage “Chance favors only the prepared mind” is a romantic oversimplification of the relationship of chance to scientific discovery. Fortunately, we may get more than one chance, and aided by interactions within our scientific communities, our minds can prepare to contribute to a new finding. So it was with the serendipitous discovery of the iron-regulatory hormone hepcidin. As a postdoctoral fellow, I studied the role of endogenous peptide antibiotics in the antimicrobial activity of phagocytes. My colleagues and I discovered and characterized a family of antimicrobial peptides of phagocytes, defensins, which eventually included defensins secreted from epithelial surfaces. In the 1990s, defensins of the human urogenital tract became the focus of my research. The predominant forms were N-terminally cleaved variants of human-β-defensin-1 (HBD-1), detected in Western blots using our laboratory-developed antibody (1). Erika Valore, a staff researcher in my laboratory, noticed that a peptide not recognized by the anti-HBD-1 antibody repeatedly appeared among the HBD-1 variants. At …