Jonathan S. Stamler, MD
Photo: Jonathan S. Stamler
Elected 1995
Jonathan Stamler is recognized for discovering protein S-nitrosylation, a ubiquitous and conserved mechanism for controlling protein function. His work has changed the understanding of cellular signaling by small gaseous messengers and broadly influenced the biological sciences. Classic tenets held that nitric oxide (NO) diffuses freely to elicit cellular signaling by binding heme in guanylate cyclase. However, S-nitrosylation (the redox reaction of NO with cysteine thiols to form S-nitrosothiols) has emerged as a unifying mechanism of NO-based signaling across scientific disciplines, regulating all main classes of proteins and serving as a prototypic redox-based signal. S-nitrosylation is thus recognized as central to the understanding of the role of NO (and redox signaling molecules) in physiology and medicine. Dr. Stamler’s insights into novel redox-based chemical biology helped create the conceptual framework of contemporary NO biology. He described the first endogenous peptide and protein S-nitrosothiols, which provided the basis for stabilization and regulation of NO bioactivity, and his work has demonstrated roles for S-nitrosylation in regulating a broad spectrum of proteins including ion channels, receptors, trafficking proteins, transcription factors and enzymes. Aberrant S-nitrosylation is causally implicated in multiple cardiovascular, respiratory, inflammatory and neurodegenerative diseases, as well as cancer. His research is notable for new insights into physiology, including the discovery of red blood cell-mediated vasodilation, which involves the S-nitrosylation of hemoglobin within the respiratory cycle (consequently re-conceptualized as a triune system: NO/O2/CO2). He has also discovered novel enzymatic machinery that regulates NO-based signaling across phylogeny (nitrosylases and denitrosylases) as well as new enzymatic functions of non-mammalian hemoglobins that process NO. Dr. Stamler’s laboratory is also known for discovering the enzymatic basis of nitroglycerin bioactivation and tolerance. His research has thus contributed fundamentally to NO/redox biology, and his elucidation in particular of S-nitrosothiol-based physiological signaling—where S-nitrosylation serves as a general mechanism for controlling protein function—has broadly impacted the biomedical sciences. Dr. Stamler attended Brandeis University, received his MD from Mount Sinai School of Medicine, and completed his internship, residency and fellowships in both Cardiovascular and Pulmonary Medicine at Harvard Medical School and Brigham and Women’s Hospital. He joined the faculty at Harvard University before spending 16 years on the faculty of Duke University. He moved to Case Western Reserve University and University Hospitals in 2010, where he holds the Reitman Family Distinguished Chair of Cardiovascular Innovation, and serves as Professor of Medicine and of Biochemistry as well as Director of the Institute for Transformative Molecular Medicine and Director of the Harrington Discovery Institute. Dr. Stamler has published more than 275 original articles and two books, co-founded five companies, licensed technology to two major pharmaceutical companies, and serves on multiple editorial and scientific advisory boards. He is the author of more than 125 patents and patent applications, and has been recognized by several prizes and awards, including recognition by the Ewing Marion Kauffman Foundation for being among the “Top Innovators in America” and by the American Heart Association as a “Distinguished Scientist.”

Honors / awards

ASCI | Stanley J. Korsmeyer Award (2000) Finalist. For elucidating the fundamental role of redox systems in the control of complex physiological responses, using NO-based modification of proteins-in particular S-nitrosylation. More