Medicine

José-Alain Sahel

Botond Roska

Jose-Alain Sahel (born in 1955, Algeria) is the chair and Distinguished Professor of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, director of the UPMC Vision Institute, and the Eye and Ear Foundation Endowed Chair of Ophthalmology and Exceptional Class Professor of Ophthalmology – Sorbonne Université.

Professor Sahel’s journey is a testament to the power of passion and dedication. He was deeply influenced by his parents, both educators, who instilled in him humanist principles and fostered a broad intellectual curiosity. Excelling across various subjects at school, Sahel displayed a natural aptitude for mathematics and physics, guided by his teachers toward the most advanced scientific pursuits. Alongside his scientific acumen, he harbored a profound appreciation for poetry and philosophy. It was this unique blend of interests that led him to choose a career in medicine.

Dr. Sahel studied medicine at the University Denis Diderot, Paris VII, and Ophthalmology at Louis Pasteur Strasbourg University. He received his medical degree with a Medal of the Faculty of Paris and obtained his specialty certification in ophthalmology. He completed a residency in Ophthalmology at the Louis Pasteur University Hospital in Strasbourg. He also was a research fellow at the Massachusetts Eye and Ear Infirmary and a visiting scholar in the Department of Molecular and Cellular Biology at Harvard University.  Dr. Sahel founded and directed the Vision Institute in Paris (2008- 2020) and is currently chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and professor at the Sorbonne’s Medical School.

Botond Roska (born in 1969, Hungary), professor at the University of Basel and director at the Institute of Molecular and Clinical Ophthalmology Basel (IOB), is a world-renowned expert in the structure and function of retinal circuits in health and disease.

Roska is the son of a musician and a computer scientist. Initially, he pursued a musical path, learning the cello and enrolling at the Franz Liszt Academy of Music from 1985 to 1989. However, an unfortunate hand injury disrupted his cello career, leading him to redirect his focus toward medicine and mathematics.

Roska earned his M.D. degree from the Semmelweis University Medical School. He pursued a Ph.D. in neurobiology at the University of California, Berkeley, and furthered his studies in genetics and virology at Harvard University Medical School. In 2005, he established a research group at the Friedrich Miescher Institute in Basel. By 2010, Roska became a Professor at the Medical Faculty of the University of Basel. Currently, he serves as a founding director at the Institute of Molecular and Clinical Ophthalmology Basel (IOB).

The global scale of visual impairment is staggering, with 217 million people having moderate to severe vision impairment and 36 million are blind. When light hits the retina (a layer of light-sensitive cells at the back of the eye), special cells in the retina known as photoreceptors, convert the light into electrical signals. These electrical signals travel from the retina through the optic nerve to the brain, where they are transformed into the images we see. Most visual disorders can be traced back to inherited and age-dependent defects in the retina. Retinitis pigmentosa (RP) is a genetic eye disease where loss of photoreceptors can lead to complete blindness. It can be triggered by defects in approximately 70 different genes and has been considered incurable until now. It is possible that the illness can be treated at an early stage by employing virus-based gene replacement therapy or by gene editing. However, this is no longer possible once blindness has become complete. Blind people lost their eye photoreceptors making the search for a solution a complex task.

Dr. Sahel is renowned for his studies on retinal genetic and complex age-related diseases leading to photoreceptor cell death and irreversible vision loss, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD). His team demonstrated the feasibility of using the photoactivatable optogene halorhodopsin delivered by a viral vector for partial vision restoration in animal and human models of retinal degeneration.

Roska developed a robust technology for cell-type targeted gene therapy and vision restoration in retinas. His laboratory generated the first single-cell transcriptome-based gene expression atlas for the human retina and choroid and then created human retinal organoids from induced pluripotent stem cells, establishing methods to generate large quantities of functional human retinal cells for optimizing gene therapy approaches ex vivo. In 2008, Roska—using gene ferries—succeeded in injecting light-sensitive channel proteins from green algae into the retinal cells of blind mice, thus giving the rodents a rudimentary form of sight.  He customized a technology to sensitize specific cell types in the eye to near-infrared light using the photoactivatable optogene channelrhodopsin ChrimsonR and demonstrated restoration of light responses in blind mice.

The two scientists met in 2001 while Roska was studying for a Ph.D. in cell and molecular biology in Berkeley, US. He had come to Strasbourg, France, to spend a month at Louis Pasteur University, where Sahel was then a laboratory director. This meeting began a long and complementary collaboration trying to reactivate photoreceptor cells in blind human retina and restore their functionality.

In a breakthrough study published in Nature Medicine in May 2021, Roska and Sahel reported the first blind patient who partially regained vision. They demonstrated the feasibility of partial vision restoration using optogenetic therapy and engineered goggles. A retinitis pigmentosa patient whose vision had been limited to rudimentary light perception regained the ability to recognize, count, locate, and touch different objects using the treated eye, following dedicated rehabilitation protocols.

While optogenetics has a nearly 20-year history in neuroscience, Sahel and Roska’s work marked the first proof-of-concept for optogenetics in any human disease and a milestone in the treatment of blinding conditions that affect millions of people worldwide.

Botond Roska and José-Alain Sahel are awarded the Wolf Prize for collectively pioneering a novel vision restoration approach by designing and applying optogenetic technology to render surviving neurons in the eye light-sensitive, functionally replacing photoreceptors lost to damage and genetic disease. This combination of powerful fundamental human neurobiological discovery research of Roska, with a deep knowledge of the clinical and translational ophthalmology of Sahel, has led to a major milestone in the fight against blindness and in the field of optogenetics more broadly.

Botond Roska

José-Alain Sahel

Jose-Alain Sahel (born in 1955, Algeria) is the chair and Distinguished Professor of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, director of the UPMC Vision Institute, and the Eye and Ear Foundation Endowed Chair of Ophthalmology and Exceptional Class Professor of Ophthalmology – Sorbonne Université.

Professor Sahel’s journey is a testament to the power of passion and dedication. He was deeply influenced by his parents, both educators, who instilled in him humanist principles and fostered a broad intellectual curiosity. Excelling across various subjects at school, Sahel displayed a natural aptitude for mathematics and physics, guided by his teachers toward the most advanced scientific pursuits. Alongside his scientific acumen, he harbored a profound appreciation for poetry and philosophy. It was this unique blend of interests that led him to choose a career in medicine.

Dr. Sahel studied medicine at the University Denis Diderot, Paris VII, and Ophthalmology at Louis Pasteur Strasbourg University. He received his medical degree with a Medal of the Faculty of Paris and obtained his specialty certification in ophthalmology. He completed a residency in Ophthalmology at the Louis Pasteur University Hospital in Strasbourg. He also was a research fellow at the Massachusetts Eye and Ear Infirmary and a visiting scholar in the Department of Molecular and Cellular Biology at Harvard University.  Dr. Sahel founded and directed the Vision Institute in Paris (2008- 2020) and is currently chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine and professor at the Sorbonne’s Medical School.

Botond Roska (born in 1969, Hungary), professor at the University of Basel and director at the Institute of Molecular and Clinical Ophthalmology Basel (IOB), is a world-renowned expert in the structure and function of retinal circuits in health and disease.

Roska is the son of a musician and a computer scientist. Initially, he pursued a musical path, learning the cello and enrolling at the Franz Liszt Academy of Music from 1985 to 1989. However, an unfortunate hand injury disrupted his cello career, leading him to redirect his focus toward medicine and mathematics.

Roska earned his M.D. degree from the Semmelweis University Medical School. He pursued a Ph.D. in neurobiology at the University of California, Berkeley, and furthered his studies in genetics and virology at Harvard University Medical School. In 2005, he established a research group at the Friedrich Miescher Institute in Basel. By 2010, Roska became a Professor at the Medical Faculty of the University of Basel. Currently, he serves as a founding director at the Institute of Molecular and Clinical Ophthalmology Basel (IOB).

The global scale of visual impairment is staggering, with 217 million people having moderate to severe vision impairment and 36 million are blind. When light hits the retina (a layer of light-sensitive cells at the back of the eye), special cells in the retina known as photoreceptors, convert the light into electrical signals. These electrical signals travel from the retina through the optic nerve to the brain, where they are transformed into the images we see. Most visual disorders can be traced back to inherited and age-dependent defects in the retina. Retinitis pigmentosa (RP) is a genetic eye disease where loss of photoreceptors can lead to complete blindness. It can be triggered by defects in approximately 70 different genes and has been considered incurable until now. It is possible that the illness can be treated at an early stage by employing virus-based gene replacement therapy or by gene editing. However, this is no longer possible once blindness has become complete. Blind people lost their eye photoreceptors making the search for a solution a complex task.

Dr. Sahel is renowned for his studies on retinal genetic and complex age-related diseases leading to photoreceptor cell death and irreversible vision loss, including retinitis pigmentosa (RP) and age-related macular degeneration (AMD). His team demonstrated the feasibility of using the photoactivatable optogene halorhodopsin delivered by a viral vector for partial vision restoration in animal and human models of retinal degeneration.

Roska developed a robust technology for cell-type targeted gene therapy and vision restoration in retinas. His laboratory generated the first single-cell transcriptome-based gene expression atlas for the human retina and choroid and then created human retinal organoids from induced pluripotent stem cells, establishing methods to generate large quantities of functional human retinal cells for optimizing gene therapy approaches ex vivo. In 2008, Roska—using gene ferries—succeeded in injecting light-sensitive channel proteins from green algae into the retinal cells of blind mice, thus giving the rodents a rudimentary form of sight.  He customized a technology to sensitize specific cell types in the eye to near-infrared light using the photoactivatable optogene channelrhodopsin ChrimsonR and demonstrated restoration of light responses in blind mice.

The two scientists met in 2001 while Roska was studying for a Ph.D. in cell and molecular biology in Berkeley, US. He had come to Strasbourg, France, to spend a month at Louis Pasteur University, where Sahel was then a laboratory director. This meeting began a long and complementary collaboration trying to reactivate photoreceptor cells in blind human retina and restore their functionality.

In a breakthrough study published in Nature Medicine in May 2021, Roska and Sahel reported the first blind patient who partially regained vision. They demonstrated the feasibility of partial vision restoration using optogenetic therapy and engineered goggles. A retinitis pigmentosa patient whose vision had been limited to rudimentary light perception regained the ability to recognize, count, locate, and touch different objects using the treated eye, following dedicated rehabilitation protocols.

While optogenetics has a nearly 20-year history in neuroscience, Sahel and Roska’s work marked the first proof-of-concept for optogenetics in any human disease and a milestone in the treatment of blinding conditions that affect millions of people worldwide.

Botond Roska and José-Alain Sahel are awarded the Wolf Prize for collectively pioneering a novel vision restoration approach by designing and applying optogenetic technology to render surviving neurons in the eye light-sensitive, functionally replacing photoreceptors lost to damage and genetic disease. This combination of powerful fundamental human neurobiological discovery research of Roska, with a deep knowledge of the clinical and translational ophthalmology of Sahel, has led to a major milestone in the fight against blindness and in the field of optogenetics more broadly.

Adrian Krainer

Joan Steitz

Lynne Maquat

“for fundamental discoveries in RNA biology that have the potential to better human lives. They have made ground-breaking discoveries in RNA regulatory mechanisms demonstrating that RNA is not a passive template between DNA and protein, but rather plays a dominant role in regulating and diversifying gene expression”.

Adrian Krainer is a professor of biochemistry and molecular genetics. Krainer’s research focuses on how splicing normally works, how it is altered in genetic diseases and cancer, and how we can correct these defects for therapy. Krainer and his team focused on finding a way to treat SMA, a neuromuscular disease that is the leading genetic cause of death in infants, by RNA therapy.

Adrian Krainer is awarded the Wolf Prize for his major contributions have advanced our understanding of the molecular mechanisms and regulation of RNA splicing.  He identified and purified the first human protein splicing factor and demonstrated its roles in constitutive and alternative splicing.  Krainer used this knowledge to study two genes, SMN1 and SMN2, associated with spinal muscular atrophy. Krainer devised an ingenious strategy to rescue the protein deficit caused by SMN1 mutations by promoting the appropriate splicing of the sister gene SMN2. This treatment received accelerated approval for use in humans and has dramatically improved the lives of thousands of children born with SMA.

Lynne Maquat

Joan Steitz

Adrian Krainer

“for fundamental discoveries in RNA biology that have the potential to better human lives. They have made ground-breaking discoveries in RNA regulatory mechanisms demonstrating that RNA is not a passive template between DNA and protein, but rather plays a dominant role in regulating and diversifying gene expression”.

Lynne Elizabeth Maquat is a professor of biochemistry and molecular biology at the University of Rochester, whose research focuses on the cellular mechanisms of human disease.

Messenger RNA (mRNA) takes genetic instructions from DNA and uses them to create proteins that carry out multiple cellular functions. NMD is a quality control mechanism that removes flawed messenger RNA molecules that, if left intact, would lead to the production of abnormal proteins that could be toxic to cells and initiate disease. Cells also use this pathway (NMD) to better respond to changing environmental conditions. NMD functions in one-third of inherited disorders, such as cystic fibrosis, and in one-third of acquired diseases, including many forms of cancer.  Her work has furthered our understanding of the molecular basis of human disease and provides valuable information to help physicians implement “personalized” or “precision” medicine by treating the disease mutation that is specific to each individual patient.

Lynne Maquat is awarded the wolf prize for discovering a mechanism that destroys mutant messenger RNA in cells, nonsense-mediated mRNA decay. Maquat studied patients with B-thalassemia and discovered that the disease-causing mutation results in pre-mature termination of B-globin mRNA translation. Maquat and colleagues demonstrated the dependence of NMD on the position of the pre-mature stop codon within the mRNA transcript, leading to the discovery of the exon junction complex. Maquat also discovered that NMD works on normal (nonmutant) transcripts and thus plays an important role in regulating on-going gene expression.

Joan Steitz

Lynne Maquat

Adrian Krainer

“for fundamental discoveries in RNA biology that have the potential to better human lives. They have made ground-breaking discoveries in RNA regulatory mechanisms demonstrating that RNA is not a passive template between DNA and protein, but rather plays a dominant role in regulating and diversifying gene expression”.

Joan Steitz is a Sterling Professor of molecular biophysics and biochemistry at Yale University and Investigator at the Howard Hughes Medical Institute.

Our DNA carries the instructions to manufacture all the proteins needed by a cell. After each gene is copied from DNA into RNA, the RNA message is “spliced” – a process involving precise cutting and pasting. Steitz has studied RNA since the 1960s and was the first to describe the translation initiation sites of prokaryotic RNA in 1969. She turned her attention to eukaryotic cells, focusing on why eukaryotic cells produce an excess of RNA in the nucleus that is not found in cytoplasm in the form of mRNA. Steitz demonstrated that ribosomes use complementary base pairing to start translating mRNA. She discovered snRNPs )small nuclear ribonucleoproteins(- small non-coding RNAs that are crucial for splicing of mRNA. Teaching and mentoring young scientists and advocating for women in science has also been a hallmark of Steitz’s career.

Joan Steitz is awarded the Wolf Prize for her many fundamental contributions to the field of RNA biology. In particular, she discovered the critical roles of small non-coding RNAs in the splicing of pre-mRNAs and the biogenesis of ribosomal RNA, and elucidated biochemical mechanisms that regulate RNA stability in eukaryotic cells. Her pioneering discoveries have laid the foundations to much of the subsequent research on RNA splicing.  

Emmanuelle Charpentier

Jennifer Doudna

Emmanuelle Charpentier (Born 1968) is a French biochemist, microbiologist and geneticist that is recognized as a world-leading expert in regulatory mechanisms underlying processes of infection and immunity in bacterial pathogens.

Together with Jennifer Doudna, led the discovery of the revolutionary gene-editing tool, CRISPR. They used this existing defense mechanism in bacteria to turn CRISPR-Cas9 into a real tool for cleaving the DNA of bacterial and also human cells. These “genetic scissors” can be used for targeting any gene in a cell in order to modify it. With this revolutionary technology, it is much easier to modify gene expression, to switch a gene “on” or “off,” or to change, repair, or remove genes. This new tool is now used in molecular biology laboratories around the world and has the potential to revolutionize medicine by paving the way to finding new forms of treatment for currently incurable diseases.

Charpentier studied biochemistry, microbiology and genetics at the University Pierre and Marie Curie, Paris, France and obtained her Ph.D. in Microbiology for her research performed at the Pasteur Institute, Paris, France. She then continued her work in the US, at The Rockefeller University, New York University Langone Medical Center and the Skirball Institute of Biomolecular Medicine (all in New York) and at St. Jude Children’s Research Hospital (in Memphis). Charpentier returned to Europe to establish her own research group as Associate Professor at The University of Vienna in Austria. She was then appointed Associate Professor at The Laboratory for Molecular Infection Medicine Sweden at Umeå University in Sweden where she habilitated in the field of Medical Microbiology. Between 2013 -2015, Charpentier was Head of the Department of Regulation in Infection Biology at the Helmholtz Centre for Infection Research, Braunschweig, and Professor at the Medical School of Hannover in Germany. In 2013, she was awarded an Alexander von Humboldt Professorship. In 2015, she was appointed Scientific Member of the Max Planck Society. From 2015 to 2018, Charpentier was Director of the Department of Regulation in Infection Biology at the Max Planck Institute for Infection Biology in Berlin, Germany. Since 2018, she is Scientific and Managing Director of the Max Planck Unit for the Science of Pathogens in Berlin, an institute that she founded together with the Max Planck Society.

The bacterial CRISPR-Cas9 system is based on an immune-like defense mechanism of action that bacteria used to protect themselves from viruses. The genome editing technique resulting from their findings immediately allowed researchers to target and cut DNA with great precision and has therefore improved the speed, efficiency and flexibility of genome editing at an unprecedented speed and ease. This new understanding already enables world-wide researchers to rapidly model human disease genes in the laboratory, accelerating the search for new drug leads and opening new doors for the treatment of human genetic disorders. These same features also call for extreme care in employing this novel technology, highlighting the need for continuous exchange of information between research scientists and policy makers for avoiding the risks involved in careless use of these unprecedented research tools.

Emmanuelle Charpentier is awarded the Wolf Prize for engaging her experties in bacterial pathogens for deciphering and repurposing the bacterial CRISPR/Cas9 immune system and its pathogen defense role for genome editing which enables its use in all live organisms on earth.

Jennifer Doudna

Emmanuelle Charpentier

Jennifer Doudna, together with the French microbiologist Emmanuelle Charpentier, led the discovery of the gene-editing tool CRISPR-Cas9. This transformative technology has the potential to eradicate previously incurable diseases and revolutionizing the fields of genetics, molecular biology and medicine.

Doudna (Born 1964) grew up in rural Hawaii, where she first became interested in the chemistry of living systems. Dr Doudna is currently the Li Ka Shing Chancellor’s Chair in Biomedical and Health Sciences and she is Professor of Molecular and Cell Biology and Professor of Chemistry at UC Berkeley and an Investigator of the Howard Hughes Medical Institute.  Professor Doudna’s research seeks to understand how RNA molecules control the expression of genetic information. Early in her career, Dr Doudna’s lab determined some of the first crystal structures of RNA and RNA-protein complexes, providing unprecedented insights into molecular function of non-protein-coding RNAs.

More recently she and her collaborator Emmanuelle Charpentier determined the mechanism of RNA-guided bacterial adaptive immunity by the CRISPR-Cas9 system, enabling them to harness this system for efficient genome engineering in animals and plants. These “genetic scissors” can be used for targeting any gene in a cell in order to modify it. With this revolutionary technology, it is much easier to modify gene expression, to switch a gene “on” or “off,” or to change, repair, or remove genes. This new tool is now used in molecular biology laboratories around the world, and has the potential to revolutionize medicine by paving the way to finding new forms of treatment for currently incurable diseases.

The bacterial CRISPR-Cas9 system is based on an immune-like defense mechanism of action that bacteria use to protect themselves from viruses.

The genome editing technique resulting from their findings immediately allowed researchers to target and cut DNA with great precision and has therefore improved the speed, efficiency and flexibility of genome editing at an unprecedented speed and ease. This new understanding already enables world-wide researchers to rapidly model human disease genes in the laboratory, accelerating the search for new drug leads and opening new doors for the treatment of human genetic disorders. These same features also call for extreme care in employing this novel technology, highlighting the need for continuous exchange of information between research scientists and policy makers for avoiding the risks involved in careless use of these unprecedented research tools.

Jennifer Doudna is awarded the Wolf Prize for her continuous research excellence which has led to her leading work that has systematically revealed both the structural elements and the medicine-revolutionizing mechanism of bacterial immunity via RNA-guided genome editing in collaboration with Emanuelle Charpentier; and for her important contribution to the ethical discussion of how this technology should best be used for ensuring successful yet humane and considerate prospects for human health and well-being.

John Kappler 

Jeffrey Ravetch

Philippa Marrack

They have made major contributions to the understanding of the key antigen-specific molecules, the T cell receptor for antigen and antibodies, and how these molecules participate in immune recognition and effector function. Working together, Drs Kappler and Marrack were instrumental in documenting that the T cell receptor recognizes antigen differently from B cells, and succeeded in identifying the previously elusive T cell receptor by an ingenious use of monoclonal T cells and monoclonal antibodies. Dr Jeffrey Ravetch has studied the heterogeneous effector function of antibody molecules and has documented the importance of diverse receptors for the constant “Fc” part of antibody molecules. He cloned many of these receptors for the immunoglobulin Fc region, and showed their importance in mediating antibody function in normal and pathological states. Together this trio has contributed much to the understanding of the molecular basis of the immune response in health and disease.

Lewis Cantley

Cantley is widely recognized for his seminal contributions to understanding growth factor signaling, cellular metabolism, and tumor formation.

Indeed, genetic aberrations in this pathway are among the most common event in human cancer.