Jeffery W. Kelly

Wolf Prize Laureate in Chemistry 2023

The 2023 Wolf Prize in Chemistry is awarded jointly to Professors Chuan He, Jeffery W. Kelly, and 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.”

 

The Wolf Prize is awarded to Jeffery W. Kelly, Scripps Research Institute, USA, for developing a clinical strategy to ameliorate pathological protein aggregation.

 

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

Wolf Prize Laureate in Chemistry 2023

The 2023 Wolf Prize in Chemistry is awarded jointly to Professors Chuan He, Jeffery W. Kelly, and 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.”

 

The Wolf Prize is awarded to Hiroaki Suga, The University of Tokyo, Japan, for developing RNA-based catalysts that revolutionized the discovery of bioactive peptides.

 

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.

Ingrid Daubechies

Wolf Prize Laureate in Mathematics 2023

The 2023 Wolf Prize in Mathematics is awarded to Ingrid Daubechies, Duke University, USA, “for work in wavelet theory and applied harmonic analysis”.

 

Ingrid Daubechies is a Belgian mathematician and physicist at Duke University in Durham, North Carolina. She earned her bachelor’s degree in physics from the Free University of Brussels in 1975. She then continued her research at the same university, earning her doctorate in physics with a thesis on the Representation of quantum mechanical operators by kernels on Hilbert spaces of analytic functions.

Ingrid Daubechies’ love for math and science was nurtured from a young age. Her father fostered her curiosity and interest in these subjects while she was in school. As a child, she was fascinated by how things worked and how to construct them, as well as the mechanisms behind machinery and the truth behind mathematical concepts. She would even calculate large numbers in her head when she couldn’t sleep, finding it captivating to see the numbers quickly grow.

Professor Ingrid Daubechies has made significant contributions to the field of wavelet theory. Her research has revolutionized the way images and signals are processed numerically, providing standard and flexible algorithms for data compression. This has led to a wide range of innovations in various technologies, including medical imaging, wireless communication, and even digital cinema.
The Wavelet theory, as presented by the work of Professor Daubechies, has become a crucial tool in many areas of signal and image processing. For example, it has been used to enhance and reconstruct images from the early days of the Hubble Telescope, to detect forged documents and fingerprints. In addition, wavelets are a vital component of wireless communication and are used to compress sound sequences into MP3 files.

Beyond her scientific contributions, Professor Daubechies also advocates for equal opportunities in science and math education, particularly in developing countries. As President of the International Mathematical Union, she worked to promote this cause. She is aware of the barriers women face in these fields and works to mentor young women scientists and increase representation and opportunities for them.

Ingrid Daubechies is awarded the Wolf Prize for her work in the creation and development of wavelet theory and modern time-frequency analysis. Her discovery of smooth, compactly supported wavelets, and the development of biorthogonal wavelets transformed image and signal processing and filtering.
Her work is of tremendous importance in image compression, medical imaging, remote sensing, and digital photography. Daubechies has also made unparalleled contributions to developing real-world applications of harmonic analysis, introducing sophisticated image-processing techniques to fields ranging from art to evolutionary biology and beyond.
Daubechies’s most important contribution is her introduction in 1988 of smooth compactly supported orthonormal wavelet bases. These bases revolutionized signal processing, leading to highly efficient methods for digitizing, storing, compressing, and analyzing data, such as audio and video signals, computed tomography, and magnetic resonance imaging. The compact support of these wavelets made it possible to digitize a signal in time linearly dependent on the length of the signal. This was a critical ingredient for researchers and engineers in signal processing to be able to rapidly decompose a signal as a superposition of contributions at various scales.
In subsequent joint work with A. Cohen and J.C. Feauveau, Daubechies introduced symmetrical biorthogonal wavelet bases. These wavelet bases give up orthonormality in favor of symmetry. Such bases are much more suitable for treating the discontinuities arising at the boundaries of finite-length signals and improving image quality. Her biorthogonal wavelets became the basis for the JPEG 2000 image compression and coding system.

Chuan He

Wolf Prize Laureate in Chemistry 2023

The 2023 Wolf Prize in Chemistry is awarded jointly to Professors Chuan He, Jeffery W. Kelly, and 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.”

 

The Wolf Prize is awarded to Professor Chuan He, The University of Chicago, USA,  for discovering reversible RNA methylation and its role in the regulation of gene expression.

 

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.