Personal Statement:
The primary focus of my laboratory and clinical investigations is to understand the mechanisms associated with retinal degeneration to develop vision restoration therapies. Together with my collaborators, I have been working on i) understanding the pathobiology of retinal conditions to further the conception, development, and evaluation of innovative treatments for retinal diseases, with a particular focus on genetic rod-cone dystrophies and age-related retinal degenerations; ii) translation to the clinic of sight-saving approaches, including neuroprotection, stem cells, gene therapy and optogenetics, pharmacology, and visual prostheses.
I founded and directed (from 2008 to 2020) the Institut de la Vision in Paris, a site for translational research on treatments for currently untreatable inherited and age-related ocular diseases that comprises 18 principal investigators and more than 300 members, functioning in synergy with the Quinze-Vingts National Eye Hospital and the Clinical Investigation Center, overseeing more than 80 clinical trials, some of them within the most advanced areas of biomedical technologies worldwide, such as retinal implants, gene therapy and optogenetics including several first-in-human trials. In 2016, I was appointed Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh Medical School and The Eye and Ear Foundation Endowed Chair. I am actively expanding the Department of Ophthalmology at the University of Pittsburgh (now more than 40 PIs), launching breakthrough trials and developing new models of care around a new translational Vision Institute (400,000 square feet, opened in May 2023) with a strong focus on vision restoration (optic nerve regeneration, prosthetics, neuroprotection, optogenetics, cortical vision). I published more than 700 peer-reviewed articles and co-authored more than 90 patents. I co-founded a dozen start-up companies: Fovea Pharmaceuticals, GenSight Biologics, Pixium Vision, Sparing Vision, SharpEye, VegaVect, Avista, Tilak, Tenpoint, SharEye, Cilensee, NetraMind. I am a Director of the Foundation Fighting Blindness Retinal Degeneration Fund and an Advisor for UPMC Enterprises and LightStone Ventures.
I serve on several editorial boards of prestigious journals such as Science Translational Medicine, the Journal of Clinical Investigation, Translational Vision Science and Technology (Associate Editor 2012-), Ophthalmology and Therapy, and Progress in Retinal and Eye Research.
I was appointed in 2023 to the newly formed Conseil Présidentiel de la Science, advising Président Emmanuel Macron and to the Conseil de l’Ordre National du Mérite.
POSITIONS, SCIENTIFIC APPOINTMENTS AND HONORS
University Positions
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2016-Present Professor and Chairman of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, The Eye and Ear Foundation Endowed Chair (Distinguished Professorship since 2019), Pittsburgh, Pennsylvania
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2023-Present Emeritus Professor of Ophthalmology, Sorbonne Université, Paris, France
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2019-Present Adjunct Professor of Ophthalmology, Hebrew University of Jerusalem, Israel
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2017-Present Adjunct Professor of Robotics and Bioengineering, Carnegie Mellon University, Pittsburgh, Pennsylvania
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2017-Present Honorary Professor, University College London, England
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2015-2016 Invited Professor at Collège de France : Chaire « Innovation Technologique», Paris, France
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2012 Visiting Professor: Hebrew University of Jerusalem, Israel
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1993-1995 Visiting Professor - Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin
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1987-1992 Visiting Lecturer in Ophthalmology - Department of Ophthalmology - Harvard Medical School, Boston, Massachusetts
Hospital Positions
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2016-Present Chairman Department of Ophthalmology, University of Pittsburgh Medical Center
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2001-Present Attending, Ophthalmology–Quinze-Vingts National Ophthalmology Hospital, Paris, France
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2001-2020 Chairman Department of Ophthalmology–Quinze-Vingts National Ophthalmology Hospital, Paris, France
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2001-2020 Chairman Department of Ophthalmology and Vitreo-Retinal Diseases–Foundation A. de Rothschild
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2005-2019 Director National Reference Centre REFERET for Inherited Retinal Dystrophies
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1988-2001 Ophthalmology-Ophthalmological Clinic–Strasbourg University Hospital, Strasbourg, France
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1994-2001 Head of the Functional Unit "Retina and Oncology" at Ophthalmology Clinic – Strasbourg University Hospital, Strasbourg, France
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1988-2002 Director of the Eye Pathology Laboratory, Louis Pasteur University, Strasbourg, France
Research Activities
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2016-Present Chairman of the University of Pittsburgh School of Medicine Ophthalmology Research Center (Vision Institute of Pittsburgh), Pittsburgh, Pennsylvania
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2024- Vice-President of the Paris Region Neuroscience BioCluster “Brain and Mind”
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2019-2024 Director Institut Hospitalo-Universitaire FOReSIGHT (50M€ Grant)
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2011-2019 Director of the Laboratory of Excellence "LIFESENSES: senses for a lifetime" (22M€ Grant)
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2009-2020 Director of the Research Centre: Vision Institute, UMR S 968 Inserm, UM80 Sorbonne Univ./ UMR 7210 CNRS
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2005-2021 Director of the Clinical Investigation Centre –503 INSERM/ Quinze-Vingts National, Paris
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2007-2017 Coordinator of the Foundation Fighting Blindness Paris Research Centre
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2006-Present Director of the “Seeing and Hearing” Institut Carnot (Vision Institute with Pasteur Institute)
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2006-2018 Director of the “Seeing and Hearing” Scientific Cooperation Foundation
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2003. Co-founder of European Vision Institute, EEIG, Brussels, Belgium
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2002-2008 Director of UMR INSERM-UPMC 592: Cellular and Molecular Physiopathology of the Retina, Paris, France
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1999-2002 Director of INSERM EMI 99-18 – UPRES EA 24-10: Cellular and Molecular Physiopathology of the retina -Louis Pasteur University, Strasbourg, France
Other Experience and Professional Memberships
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Director, The Foundation Fighting Blindness Retinal Degeneration Fund; Advisor, UPMC Enterprises, LightStone Ventures
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Journal editorial boards: Journal of Clinical Investigation; Science Translational Medicine; Progress in Retinal and Eye Research; Translational Vision Science and Technology (Associate Editor 2012-present); Ophthalmology and Therapy
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Member of Conseil Présidentiel de la Science, advising Président Emmanuel Macron (2023-present)
- 1976-1980 Medical School - Paris University Medical School, Paris, France
- 1979-1980 Ophthalmology Residency - Rothschild Ophthalmology Foundation, Paris, France
- 1980-1984 Neurosurgery Residency - Louis Pasteur University Hospital, Strasbourg, France
- 1984-1988 Clinical Fellowship - Louis Pasteur University Hospital, Strasbourg, France
- 1986-1987 Research Fellowship - Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts
- 1987 Visiting Scholar - Harvard Biological Laboratories, Department of Cellular and Developmental Biology, Harvard University, Cambridge, Massachusetts
Education & Training
Awards & Memberships
Dr. José Sahel has received numerous awards, including the 2024 Wolf Prize in Medicine and the EURORDIS 2024 Black Pearl Scientific Awards, the 2024 Michaelson Award from the Macula Society, the 2023 International Prize for Translational Neuroscience from the Max Planck Society, Germany (with Botond Roska), the 2022 Chica and Heinz Schaller Foundation Award for Translational Neuroscience, the 2021 Breakthrough in the Life Sciences - Falling Walls Foundation, Berlin, Germany, the 2015 Llora and Gordon Gund Award from Foundation Fighting Blindness, the 2012 Innovation Medal of Centre National de la Recherche Scientifique, The 2006 NRJ Grand Prix Scientifique de Neurosciences-Académie des Sciences-Institut de France and the 2006 Alcon Award for Excellence in Ophthalmology, among others.
He was was elected to The Académie des Sciences-Institut de France (2007), the Academia Ophthalmologia Internationalis (2007), The German National Academy of Sciences Leopoldina (2015), the Association of Americal Physicians (2018), and a Fellow of the National Academy of Inventors (2023).
(Please see attached NIH biosketch below for a full list of Dr. Sahel’s awards and memberships.)
RESEARCH INTEREST SUMMARY:
Retinal disease treatments including Rod-derived-Cone-Viability-Factor, translation/research on molecular and genetic factors in retinal disease progression and treatment/regenerative therapeutic treatments for retinal disease/research on retinal cell types for optogenetic treatments.
José-Alain Sahel is a clinician-scientist conducting research on vision restoration focusing on cellular and molecular mechanisms underlying retinal degeneration, and development of treatments for currently untreatable retinal diseases. José-Alain Sahel’s work has contributed to understanding and preventing vision loss from photoreceptor cell degeneration and developing several novel vision restoration strategies. His clinical research is closely entangled with experimental research (information processing, genetic therapeutic research including modeling), evidence of pre-clinical concepts, technological developments in imaging and surgery, and forming integrated site research on diseases of vision. He conducted dozens of clinical trials on retinal conditions and led several first-in-human vision restoration clinical trials in gene therapy, retinal prosthesis and optogenetics.
Research Interests
1. Together with my team, I worked on the conception, development, and evaluation of innovative treatments for retinal diseases -with a special focus on genetic rod-cone dystrophies- including neuroprotection, stem cells, gene therapy, pharmacology, and artificial retina. I was the first to hypothesize and demonstrate that rod photoreceptors produce a protein that rescues cone photoreceptors, thereby maintaining light-adapted and high-resolution vision. We (with S. Mohand-Said and Thierry Leveillard) identified the underlying signal: Rod-derived Cone Viability Factor (RdCVF) and determined its mechanisms of action (stimulation of aerobic glycolysis, and antioxidant).
a. Mohand-Said S, Deudon-Combe A, Hicks D, Simonutti M, Forster V, Fintz AC, Léveillard T, Dreyfus H, Sahel JA. Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse. Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8357-62
b. Mohand-Saïd S, Hicks D, Léveillard T, Picaud S, Porto F, Sahel JA. Rod-cone interactions: development and clinical significance. Prog Retin Eye Res 2001; 20: 451-67.
c. Léveillard T, Mohand-Saïd S, Lorentz O, Hicks D, Fintz AC, Clérin E, Simonutti M, Forster V, Cavusoglu N, Chalmel F, Dollé P, Poch O, Lambrou G, Sahel JA. Identification and characterization of rod-derived cone viability factor. Nat Genet. 2004 Jul;36(7):755-9.
d. Aït-Ali N, Fridlich R, Millet-Puel G, Clérin E, Delalande F, Jaillard C, Blond F, Perrocheau L, Reichman S, Byrne LC, Olivier-Bandini A, Bellalou J, Moyse E, Bouillaud F, Nicol X, Dalkara D, van Dorsselaer A, Sahel JA, Léveillard T. Rod-derived Cone Viability Factor acts by stimulating aerobic glycolysis. Cell, 2015 May 7;161(4):817-32.
2. RdCVF use is now in translation as a possible therapeutic agent to save cones and treat a spectrum of retinal degenerative diseases as a mutation independent strategy.
a. Yang Y, Mohand-Said S, Danan A, Simonutti M, Fontaine V, Clerin E, Picaud S, Léveillard T, Sahel JA. Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa. Mol Ther. 2009 May;17(5):787-95.
b. Léveillard T, Sahel JA. Rod-derived cone viability factor for treating blinding diseases: from clinic to redox signaling. Science Translational Medicine. 2010 Apr 7;2(26):26ps16.
c. Byrne LC, Dalkara D, Luna G, Fisher SK, Clérin E, Sahel JA, Léveillard T, Flannery JG. Viral-mediated RdCVF and RdCVFL expression protects cone and rod photoreceptors in retinal degeneration. J Clin Invest. 2015;125(1):105-16.
d .Sahel JA, Bennett J, Roska B. Depicting brighter possibilities for treating blindness. Sci Transl Med. 2019 May 29;11(494). pii: eaax2324. The IND for the clinical trial has been granted in 2022.
3. Utilizing a variety of molecular and functional genomics approaches, my group aims to identify novel disease causing genes for retinal degenerations. Besides research on developmental biology, functional genomics, physiology and therapeutics, my team (with M.Paques, S. Mohand-Said and I. Audo) conducts research on genotype-phenotype correlations with high resolution in vivo non-invasive high-resolution retinal imaging techniques (optical coherence tomography and adaptive optics) aiming at identifying patients eligible for clinical application of innovative therapies. Together with M. Fink (Institut Langevin), I led a very competitive, large, ERC-Synergy grant (2014-2021) aiming at developing novel technologies for morpho-functional imaging of the visual system.
a.Roska B, Sahel JA. Restoring vision. Nature. 2018 May;557(7705):359-367
b.Blaize K, Arcizet F, Gesnik M, Ahnine H, Ferrari U, Deffieux T, Pouget P, Chavane F, Fink M, Sahel JA, Tanter M, Picaud S Functional ultrasound imaging of deep visual cortex in awake nonhuman primates. Proc Natl Acad Sci U S A. 2020 Jun 23;117(25):14453-14463
c.Sahel JA, Grieve K, Pagot C, Authié C, Mohand-Said S, Paques M, Audo I, Becker K, Chaumet-Riffaud AE, Azoulay L, Gutman E, Léveillard T, Zeitz C, Picaud S, Dalkara D, Marazova K. Assessing photoreceptor status in retinal dystrophies: from high resolution imaging to functional vision. Am J Ophthalmol. 2021 : S0002-9394(21)00212-9
d.Verschueren A., Boucherit L., Ferrari U., Fouquet S., Nouvel-Jaillard C., Paques M., Picaud S., Sahel JA. Planar polarity in primate cone photoreceptors: a potential role in Stiles Crawford effect phototropism, Commun Biol 5, 89 (2022)
4. We’ve developed a number of regenerative therapeutic approaches to restore vision such as gene therapy (including the first advanced trials on mitochondrial diseases) leading to the first demonstration in several large scale randomized trials of the efficacy of Gene Therapy in Leber Hereditary Optic Neuropathy.
a. Vignal C, Uretsky S, Fitoussi S, Galy A, Blouin L, Girmens JF, Bidot S, Thomasson N, Bouquet C, Valero S, Meunier S, Combal JP, Gilly B, Katz B, Sahel JA. Safety of rAAV2/2-ND4 Gene Therapy for Leber Hereditary Optic Neuropathy. Ophthalmology. 2018 Jun;125(6):945-947.
b. Newman NJ, Yu-Wai-Man P, Carelli V, Moster ML, Biousse V, Vignal-Clermont C, Sergott RC, Klopstock T, Sadun AA, Barboni P, DeBusk AA, Girmens JF, Rudolph G, Karanjia R, Taiel M, Blouin L, Smits G, Katz B, Sahel JA. Efficacy and Safety of Intravitreal Gene Therapy for Leber Hereditary Optic Neuropathy Treated within 6 Months of Disease Onset. LHON Study Group. Ophthalmology. 2021 May;128(5):649-660.
c. Yu-Wai-Man P, Newman NJ, Carelli V, Moster ML, Biousse V, Sadun AA, Klopstock T, Vignal-Clermont C, Sergott RC, Rudolph G, La Morgia C, Karanjia R, Taiel M, Blouin L, Burguière P, Smits G, Chevalier C, Masonson H, Salermo Y, Katz B, Picaud S, Calkins DJ, Sahel JA. Bilateral Visual Improvement with Unilateral Gene Therapy Injection for Leber Hereditary Optic Neuropathy. Science Translational Medicine Dec 9; 12 (573) 2021: eaaz7423.
d. Nancy J Newman, Patrick Yu-Wai-Man, Prem S Subramanian, Mark L Moster, An-Guor Wang, Sean P Donahue, Bart P Leroy, Valerio Carelli, Valerie Biousse, Catherine Vignal-Clermont, Robert C Sergott, Alfredo A Sadun, Gema Rebolleda Fernández, Bart K Chwalisz, Rudrani Banik, Fabienne Bazin, Michel Roux, Eric D Cox, Magali Taiel, José-Alain Sahel, the LHON REFLECT Study Group, Randomized trial of bilateral gene therapy injection for m.11778G>A MT-ND4 Leber optic neuropathy, Brain, 2022;, awac421, https://doi.org/10.1093/brain/awac421
5. With B. Roska at the Institute of Ophthalmology of Basel, S.Picaud and Deniz Dalkara at Institut de la Vision in Paris, we demonstrated that different retinal cell types such as "dormant cones" and Ganglion Cells can be converted into “artificial photoreceptors” by targeting the expression of genetically encoded light sensors enabling mice with retinal degeneration to perform visually guided behaviors. I led the first demonstration of the efficacy of Optogenetics in partial function restoration in humans. I also led (with Dr. Palanker) the first in-human wireless artificial retina trial.
a. Busskamp V, Duebel J, Balya D, Fradot M, Viney TJ, Siegert S, Groner AC, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Paques M, Mohand-Said S, Trono D, Deisseroth K, Sahel JA, Picaud S, Roska B. Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis pigmentosa. Science. 2010 329(5990):413-7.
b. Palanker D, Le Mer Y, Mohand-Said S, Muqit M, Sahel JA. Photovoltaic Restoration of Central Vision in Atrophic Age-Related Macular Degeneration. Ophthalmology. 2020 Feb 25: S0161-6420(20)30189-5.
c. Sahel JA, Boulanger-Scemama E, Pagot C, Arleo A, Galuppi F, Martel JN, Degli Esposti S, Delaux A, de Saint Aubert JB, de Montleau C, Gutman E, Audo I, Duebel J, Picaud S, Dalkara D, Blouin L, Taiel M, Roska B. Partial recovery of visual function in a blind patient after optogenetic therapy. Nature Medicine 2021 Jul;27(7):1223-1229.
d. Palanker D, Le Mer Y, Mohand-Said S, Sahel JA. Simultaneous Perception of Prosthetic and Natural Vision in AMD Patients, Nature Communications, (2022) 13:513