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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.

Hiroaki Suga

Jeffery W. Kelly

Chuan He

“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. Suga received his Bachelor of Engineering (1986) and Master of Engineering (1989) from Okayama University, Ph.D. in Chemistry (1994) from MIT, and was a post-doctoral fellow at the Massachusetts General Hospital. Suga began his independent career at New York State University at Buffalo (1997-2003). In 2003 he moved to the Research Center for Advanced Science and Technology at the  University of Tokyo. Since 2010 Suga has been a full Professor in the department of chemistry at the University of Tokyo. Currently, he serves as the President of the Chemical Society of Japan.

Prof. Suga’s research interests include bioorganic chemistry, chemical biology, and biotechnology related to RNA, translation, and peptides. As a young researcher, he made significant advances in using RNA-based enzymes, or ribozymes, to incorporate unnatural amino acids into tRNA. This technology, known as the “Flexizyme,” greatly expanded the potential for reprogramming the genetic code. Through additional research on in vitro translation of proteins using reconstituted ribosomes, Prof. Suga could incorporate various unnatural amino acids into expressed peptides to spontaneously produce molecules that form macrocyclic peptides. Prof. Suga used oligonucleotide display and directed evolution to create the RaPID system, a platform for producing and selecting billions of macrocyclic peptides as high-affinity binders to protein targets, including many that had previously been considered undruggable.

In 2006, Prof. Suga co-founded PeptiDream to advance and apply the RaPID system, which quickly became a widely used technology for finding small molecule protein binders, particularly disrupting protein-protein interactions. His discoveries have enabled the construction of complex molecules on a large scale, not possible using conventional methods alone. Suga’s work has produced more unique non-natural molecules than other approachs, which possess the unique stereochemistry, rich functional group density, and 3D-architecture necessary for interrogating and controlling biological processes. This paved the way for a new generation of drugs. PeptiDream became a publicly traded company on the Tokyo Stock Exchange and is one of Japan’s most successful startup companies.

Hiroaki Suga is awarded the Wolf prize for developing an exceptionally innovative in-vitro selection system for cyclic peptides as inhibitors of protein-protein interactions. He invented an RNA-based catalyst, flexizyme, that transcends natural mechanisms and vastly expands the range of amino acids that can be incorporated with ribosomal machinery. Suga’s strategy enables rapid construction and screening of enormous cyclic peptide libraries. His unique discovery has established a new approach to medicinal chemistry and generated new tools for drug discovery.

Chuan He

Jeffery W. Kelly

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”.

Chuan He is a Chinese-American chemical biologist, the John T. Wilson Distinguished Service Professor at the University of Chicago, and an Investigator at the Howard Hughes Medical Institute. He graduated from the University of Science and Technology of China with a B.S. in Chemistry (1994), Ph.D. at MIT, and postdoctoral research at Harvard University. He joined the Department of Chemistry at the University of Chicago in 2002 and served as the Director of the Institute for Biophysical Dynamics (2012 -2017).

More than 150 structurally distinct post-transcriptional modifications of cellular RNA molecules occur at thousands of sites. Some of these modifications are dynamic and may have critical regulatory roles analogous to protein and DNA modifications. Therefore, understanding the scope and mechanisms of dynamic RNA modifications represents an emerging research frontier in biology and medicine.

Prof. Chuan He is a world-class expert studying RNA’s post-transcriptional modifications, the role these modifications play in cellular processes, and their broad impact on mammalian development and human diseases. His research, spanning a wide range of chemical biology, nucleic acid chemistry, biology, epigenetics, and bioinorganic chemistry, focuses on understanding both RNA and DNA’s modifications and their roles in regulating gene expression.
He was the first to champion the idea that RNA modifications are reversible and can control gene expression. His work is fundamental in developing potential therapies that target RNA methylation effectors against human diseases such as cancer. His research group was the first to identify proteins that can erase, and undo changes made to RNA molecules, which sparked the emergence of the epitranscriptome field. Prof. He explained how RNA methylation functions through characterizing reader proteins—processes that play critical roles in many types of cancer, including endometrial cancer, acute myelogenous leukemia, and glioblastoma.

Chuan He is awarded the Wolf prize for his pioneering work elucidating the chemistry and functional consequences of RNA modification. He discovered reversible RNA methylation, leading to a conceptual breakthrough regarding the functional roles of RNA modifications in the regulation of gene expression. The He laboratory discovered the first RNA demethylase, an enzyme that removes the methyl group from N6-methyladenosine, the most prevalent mRNA modification in eukaryotes.