University of Pennsylvania Health System

Department of Ophthalmology

Ophthalmology Faculty

Faculty Overview

Jean Bennett, MD, PhD

faculty photo
F.M. Kirby Professor of Ophthalmology
Professor, Department of Cell and Developmental Biology, University of Pennsylvania
Vice Chair for Basic Research, Department of Ophthalmology, University of Pennsylvania
Department: Ophthalmology

Contact information
310 Stellar-Chance Labs
422 Curie Blvd.
Philadelphia, PA 19104
Graduate Group Affiliations
Education:
B.S. (Honors Biology)
Yale University , 1976.
Ph.D. (Zoology; Cell and Developmental Biology)
University of California at Berkley, 1980.
M.D.
Harvard University, 1986.
Post-Graduate Training
Postdoctoral Fellow, Lab. of Radiobiology and Environmental Health, University of California, San Francisco; Mentor: Dr. Roger Pedersen., 1980-1982.
Summer Research Fellow, Laboratory of Molecular Hematology, Mentor: Dr. French Anderson., National Institutes of Health, 1983-.
National Board of Medical Examiners, Part I, (passed), National Board of Medical Examiners, 1984-.
National Board of Medical Examiners, Part II, (passed), National Board of Medicine Examiners, 1985-.
Postdoctoral Fellow, Dept. of Human Genetics, Yale University; Mentor: Dr. Leon Rosenberg., 1986-1987.
Stetler Fellow, Lab of Developmental Genetics, Dept. of Physiology, Johns Hopkins Medical School; Mentor: Dr. John Littlefield, Dr. John Gearhart., 1987-1989.
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Description of Research Expertise

Research Interests
- Molecular genetics of retinal degenerations.
- Gene therapy-mediated treatment of ocular disease.

Key words: Retina, Neovascularization, Neuronal Degeneration, Gene Therapy, Viral Vector, AAV, Lentivirus, Adenovirus, Vision, Animal Models, Eye, Immune Response.

Description of Research
Jean Bennett studies the molecular genetics of inherited retinal degenerations with the idea of using this knowledge to develop rational approaches for treatment of these diseases. Target diseases include retinitis pigmentosa and age-related macular degeneration. Studies in her laboratory range from identifying the molecular bases of retinal degenerations, generating animal models for these diseases, evaluating novel vectors for retinal gene transfer, characterizing immune responses to gene transfer, developing novel gene-based approaches for reversal of sensory loss, and rescuing vision in animal models through gene based treatments. Dr. Bennett was one of the first investigators to use viral vectors to deliver transgenes to specific cells in the retina and also led the first team to demonstrate proof-of-principle of ocular gene therapy. She has developed a number of strategies for gene therapy-mediated treatments for retinal disease. Besides the eye, projects in Dr. Bennett's laboratory target other diseases/organs suffering from mutations in cilia proteins, including the ear (cochlea) and the kidney (renal tubular epithelium). Dr. Bennett's work leads naturally to translational research. For example, a study conducted in her lab and with collaborators at UPenn, Cornell and University of Florida led to a remarkable reversal of blindness in a canine model of a blinding disease affecting infants. This treatment is currently being tested in human clinical trials at several different Centers. Dr. Bennett is Scientific Director for the Phase I/II human clinical trial evaluating the safety and efficacy of gene transfer in Leber congenital amaurosis (LCA) due to RPE65 mutations. This trial is being carried out at The Children's Hospital of PHiladelphia (CHOP). This was the first study to report the exciting efficacy results in all twelve subjects, including 5 children.

Rotation Projects for 2010-2011
Gene therapy for an inherited retinal degeneration; Gene therapy for retinal neovascularization; Generation of a mouse model for an inherited macular degeneration; Gene therapy for Leber Congenital Amaurosis, Gene Therapy for autosomal recessive Stargartd Disease; Gene Therapy for Choroideremia; Immune response to subretinal readministration of gene therapy vectors; Identification of novel genes causing retinal degeneration; Gene Therapy for Usher's Syndrome (blindness and deafness)

Lab personnel:

Aaron Black
Jeannette Bennicelli
Ik Joon Chang
Daniel Chung
Rob Collin (visiting from Rabhoud University, The Netherlands)
Therese Cronin
Arkady Lyubarsky
Jessica Morgan
Albert Maguire
William M. Maguire
Mihaela Petrova
Pyroja Sulaiman
Mohammed Toure
Zhangyong Wei

Description of Clinical Expertise

Translational research on retinal degenerations

Selected Publications

Testa Francesco, Maguire Albert M, Rossi Settimio, Marshall Kathleen, Auricchio Alberto, Melillo Paolo, Bennett Jean, Simonelli Francesca: Evaluation of Ocular Gene Therapy in an Italian Patient Affected by Congenital Leber Amaurosis Type 2 Treated in Both Eyes. Advances in experimental medicine and biology 854: 533-9, 2016.

Sochor Matthew A, Vasireddy Vidyullatha, Drivas Theodore G, Wojno Adam, Doung Thu, Shpylchak Ivan, Bennicelli Jeannette, Chung Daniel, Bennett Jean, Lewis Mitchell: An Autogenously Regulated Expression System for Gene Therapeutic Ocular Applications. Scientific reports 5: 17105, Nov 2015.

Pierce Eric A, Bennett Jean: The Status of RPE65 Gene Therapy Trials: Safety and Efficacy. Cold Spring Harbor perspectives in medicine 5(9): a017285, Sep 2015.

Ashtari Manzar, Zhang Hui, Cook Philip A, Cyckowski Laura L, Shindler Kenneth S, Marshall Kathleen A, Aravand Puya, Vossough Arastoo, Gee James C, Maguire Albert M, Baker Chris I, Bennett Jean: Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis. Science translational medicine 7(296): 296ra110, Jul 2015.

Drivas Theodore G, Wojno Adam P, Tucker Budd A, Stone Edwin M, Bennett Jean: Basal exon skipping and genetic pleiotropy: A predictive model of disease pathogenesis. Science translational medicine 7(291): 291ra97, Jun 2015.

Palfi Arpad, Chadderton Naomi, O'Reilly Mary, Nagel-Wolfrum Kerstin, Wolfrum Uwe, Bennett Jean, Humphries Peter, Kenna Paul, Millington-Ward Sophia, Farrar Jane: Efficient gene delivery to photoreceptors using AAV2/rh10 and rescue of the Rho(-/-) mouse. Molecular therapy. Methods & clinical development 2: 15016, May 2015.

Ramachandran Pavitra S, Song Ji Yun, Bennett Jean: Exploiting metabolic and antioxidant pathways to maintain vision in blinding disease. The Journal of clinical investigation 125(4): 1390-2, Apr 2015.

Minella A L, Mowat F M, Willett K L, Sledge D, Bartoe J T, Bennett J, Petersen-Jones S M: Differential targeting of feline photoreceptors by recombinant adeno-associated viral vectors: implications for preclinical gene therapy trials. Gene therapy 21(10): 913-20, Oct 2014.

Bennett Johan, De Cock Dries, Hiltrop Nick, Adriaenssens Tom: Unusual stent fracture: diagnosis with optical coherence tomography. Journal of cardiovascular medicine (Hagerstown, Md.) Sep 2014.

Morgan Jessica I W, Han Grace, Klinman Eva, Maguire William M, Chung Daniel C, Maguire Albert M, Bennett Jean: High-resolution adaptive optics retinal imaging of cellular structure in choroideremia. Investigative ophthalmology & visual science 55(10): 6381-97, Sep 2014.

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Last updated: 12/07/2015
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