Jeffery W. Kelly
Wolf Prize Laureate in Chemistry 2023
Jeffery W. Kelly
Affiliation at the time of the award:
Scripps Research Institute, USA
Award citation:
“for developing a clinical strategy to ameliorate pathological protein aggregation”.
Prize share:
Jeffery W. Kelly
Chuan He
Hiroaki Suga
“for pioneering discoveries that illuminate the functions and pathological dysfunctions of RNA and proteins and for creating strategies to harness the capabilities of these biopolymers in new ways to ameliorate human diseases”.
Prof. Jeffery W. Kelly is the Lita Annenberg Hazen Professor of Chemistry at The Scripps Research Institute. Kelly received his BS in chemistry from the State University of New York at Fredonia, his Ph.D. in organic chemistry from the University of North Carolina at Chapel Hill (1986), and performed postdoctoral research in bio-organic chemistry at Rockefeller University (1989).
Most protein molecules must fold into defined three-dimensional structures to acquire their functional activity. However, some proteins can adopt several folding states, and their biologically active state may be only marginally stable. Misfolded proteins can form toxic aggregates, such as soluble oligomers and fibrillar amyloid deposits, which may lead to neurodegeneration in Alzheimer’s disease and many other pathologies. All cells contain an extensive protein homeostasis network of protein folding devices, such as molecular chaperones and other factors that prevent or regulate protein aggregation. These defense networks tend to decline during aging, facilitating the manifestation of aggregate deposition diseases.
Prof. Kelly’s research focuses on understanding protein folding, misfolding, and aggregation and using chemical and biological approaches to develop novel therapeutic strategies to combat diseases caused by protein misfolding and aggregation. He contributed significantly to the fight against neurodegenerative diseases by discovering the mechanism of protein aggregation in amyloid diseases that affect the heart and nervous system. He showed the mechanism by which a protein, transthyretin, unravels and agglomerates into clusters that kill cells, tissues, and ultimately patients and developed a molecular approach to stabilize this protein.
Kelly successfully synthesized the first regulatory-agency-approved drug, “tafamidis vyndaqel”. This pioneering drug, marketed worldwide, significantly slows the progression of Familial Amyloid Polyneuropathy, a neurodegenerative disease, and Familial and Sporadic TTR Cardiomyopathy disease, which causes heart failure.
Jeffery W. Kelly is awarded the Wolf prize for developing a new and clinically impactful strategy to ameliorate disease caused by pathological protein aggregation. His seminal contributions revealed fundamental features of protein homeostasis (proteostasis) at the molecular level, including the interplay among protein folding, misfolding, and aggregation. Dysregulation of proteostasis is associated with a spectrum of human diseases. Kelly’s laboratory used these fundamental insights to develop the drug “tafamidis”, which halts or slows disease progression in patients suffering from transthyretin amyloidosis. This approach may be applicable to other proteostasis-based disorders.
