The Wolf Prize laureates

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.

Fujiko Nakaya

Sir Richard Julian Long

Fujiko Nakaya was born in Sapporo, Japan. Her early interest in the connections between art and science was inspired by her father’s work and his belief that the realization of scientific truths depended on collaboration between human beings and nature. Like her father, a physicist renowned for his work in glaciology and snow crystal photography, Nakaya’s lifelong artistic investigation engages the element of water and instills a sense of wonder in everyday weather phenomena.

Fujiko Nakaya studied at the High School of Japan Women’s University in Tokyo and at Northwestern University in Evanston, Illinois. Her first solo exhibition was held at the Tokyo Gallery in 1962. Her work took a significant turn when she joined the Experiments in Art and Technology collective of artists and engineers (E.A.T.).

A bridge between the metaphysical and physical world, the fog has fascinated by its ability to blur the boundaries between reality and imagination. For Nakaya, it “makes visible things become invisible and invisible things—like wind—become visible.”
Working as part of the collective, she enshrouded the Pepsi Pavilion at the 1970 World Exposition in Osaka in vaporous fog, becoming the first artist to create a sculptural fog environment. Nakaya has worked with artificial fog extensively since, creating fog sculptures, and developing immersive and unstable environments, making her a pioneer of the genre. Nakaya is widely known for her early experiments in art and technology, as well as her work in video art. She co-founded the collective Video Hiroba and opened Japan’s first video art gallery. She has collaborated with many international artists and has participated in many international exhibitions.

Fujiko Nakaya, one of Japan’s leading artists, is awarded the Wolf Prize for being a longtime pioneer of work that intermingles the realms of art, nature, science, and technology. Her sculptures, films and videos, installations, and paintings, produced over a seven-decade career, engage fundamental subjects such as the environment, perception, and communication. Nakaya’s early concern with the artistic potential of natural resources, her embrace of nascent technologies, and her exploration of human interaction with our planet, have proven remarkably prescient. Half a century after she first developed the concept of fog sculptures, she continues to astonish audiences with the magic of work made at the junction of art and nature, poetry and science. At heart Nakaya is an experimentalist who disregards predetermined categories and, in so doing, expands the definition and experience of art.

Sir Richard Julian Long

Fujiko Nakaya

Sir Richard Julian Long is an English sculptor and one of the best-known British land artists. He lives and works in Bristol, the city in which he was born. Long studied at the West of England College of Art (1962-1965) and continued his studies at the St. Martin’s School of Art and Design, London (1966-1968). Considered one of the most influential artists, Richard Long’s works have extended the possibilities of sculpture beyond traditional materials and methods. Long’s works engage with the landscape, investigating nature and his experience within nature. His work is typically displayed with materials or through documentary photographs of his performances and experiences.

When Richard Long was 18, he walked on the downs near his native Bristol. He began rolling a snowball through the snow, and when it became too big to push further, he took out his camera – then, instead of snapshotting the giant snowball, he photographed the dark meandering track it had left in the snow. This image, one of his earliest works of land art, was named “Snowball Track”. He was then a student at the West of England College of Art in Bristol, but he was dismissed from the course because his work was considered too provocative and perhaps ahead of its time.

Walking is central to Long’s work as a way of perceiving and recording landscape; early in his career, he established the precedent that art could be a journey and that a sculpture could be deconstructed over the distance of a journey. Walking as a medium has enabled him to articulate ideas about time and space. He seeks freedom of movement and expression and a balance with the natural world through a physical and personal engagement with the land, working with nature to reflect its impermanence and the changing processes of time. His beguilingly simple works commonly take the form of geometric shapes-circles, lines, ellipses, and spirals and use raw materials,
such as stones and driftwood, found along the way. These works are often simple interventions, marks of passage, and leave little or no trace, and are documented through photographs or text works that record his ideas, observations, and experiences.

Richard Long is awarded the Wolf Prize for being a pioneer of conceptual art centered on personal interaction with the natural world. In 1967, his work A Line Made by Walking introduced a contemporary reimagining of human experience in nature as a subject for art. Over the course of nearly six decades, his solitary walks throughout the world have generated a complex body of work comprising sculptures, photographs, drawings, and texts. The materials for these artworks, echoing the walks themselves, are nature-based: rocks and stones, logs and twigs, mud and soil. The tools of time-marking and map-making, place-naming and record-keeping all figure together to create works that commingle factual observation and artistic invention. Long’s deep engagement with the natural environment as process, subject, material, and vocabulary has established him as a key figure of his generation and one whose work resonates powerfully with present-day concerns.

Benjamin F. Cravatt

Carolyn Bertozzi

Bonnie Bassler

“for their seminal contributions to understanding the chemistry of cellular communication and inventing chemical methodologies to study the role of carbohydrates, lipids, and proteins in such biological processes”.

Cravatt, the Gilula Chair of Chemical Biology and Professor in the Department of Chemistry at The Scripps Research Institute. His research aims to understand proteins’ roles in human physiological and pathological processes and use this knowledge to identify novel therapeutic targets and drugs to treat diseases.

Cravatt was inspired to think about biology by his parents and credits his high school mathematics teachers for nurturing his interest in the quantitative sciences. Cravatt obtained his undergraduate education at Stanford University, receiving a B.Sc in Biology and a B.A. in History. He then received a Ph.D. from The Scripps Research
Institute (TSRI) in 1996 and joined the faculty at TSRI in 1997.

Bridging the fields of chemistry and biology, Cravatt and his research group have developed and applied technologies to discover biochemical pathways in mammalian biology and disease. Cravatt pioneered an approach to identify protein classes based on their activity. His multidisciplinary approach generates all tools and models required to assign molecular, cellular, and physiological functions to enzymes and, as an essential corollary, assess their suitability as therapeutic targets. He achieves a unique balance that cultivates the creation and rapid implementation of cutting-edge technologies to advance basic and translational science.

Cravatt’s work on the endocannabinoid system has radically changed the landscape of proteome analysis by demonstrating how innovative chemical methods can be used to broadly and deeply investigate protein function directly in native biological systems.

The chemical proteomic technology Activity-Based Protein Profiling (ABPP), pioneered by Cravatt employs chemical probes to directly measure enzyme function. For example, a fluorescent label may be used to tag enzymes with certain chemical properties, allowing scientists to survey all active enzymes in a cell at once, and to determine
the targets of drugs in a global manner directly in living systems.

Cravatt has used this and related chemical proteomic technologies to conduct global analyses of protein activities and to elucidate the functions of several enzymes, including those linked to human cancers, neurological disorders, and the endocannabinoid system, which consists of lipid transmitters involved in appetite regulation, pain sensation, mood, memory, and other physiological processes.

Benjamin Cravatt is awarded the Wolf prize for developing activity-based protein profiling, which has emerged as a powerful and widely used chemical proteomic strategy to characterize enzyme function in native biological systems. He used this approach to characterize numerous enzymes which play critical roles in human biology and disease, including the endocannabinoid hydrolases whose lipid products regulate communication between cells.