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University of Pennsylvania Health System

Department of Ophthalmology

 

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Ophthalmology Education

 

 

Penn Vision Clinical Scientist Program

Mentors

Mentors include:


Jean Bennett, MD, PhD
Artur Cideciyan, PhD
Samuel Jacobson, MD, PhD
Maureen Maguire, PhD

Jean Bennett, MD, PhD

Dr. Bennett is leading several major research efforts in retinal disease and has effectively incorporated medical students, graduate students, residents, clinical fellows, and post-doctoral fellows in both short-term (3-6 month) and long-term research projects. Her efforts continue to develop, characterize and improve viral vectors that could be used for evaluating biological mechanisms that normally occur in the retina and for gene therapy applications. Work has continued on adeno-associated virus (AAV) vectors generated with capsids of different AAV serotypes.

Dr. Bennett's laboratory has evaluated six genes for prospects for gene therapy for haploinsufficiency, PDEb, RHO (AR-RP), RPE65 (Leber Congenital Amaurosis), REP-1 (choroideremia) and MPSVI (mucopolysaccharidosis VI) and MPSVII and developed methods for delivering the viral vectors at early postnatal/fetal time points in the diseases that have a rapid onset of degeneration (AR-RP). Gene therapy studies for RPE65 mutations causing Leber Congenital Amaurosis (LCA) continue to be successful, leading to the funding of a multi-investigator, multi-center research/clinical plan to develop viral vector-based gene therapy for RPE65 Leber congenital amaurosis (LCA) and to begin phase I/II clinical testing. Dr. Bennett leads module 3, Identification of the ideal vector for human studies using the RPE65-/- mouse.

Other recent accomplishments that continue to be explored in the laboratory include:

  • Developing methods for in utero retinal gene therapy in the mouse allowing testing of gene therapy for early onset severe blinding diseases
  • Development of methods to correct single base pair mutations in somatic cells
  • Successful use of gene therapy techniques to inhibit retinal neovascularization in animal models of retinopathy of prematurity and of choroidal neovascularization.

With such an extensive research laboratory, Dr Bennett will be able to provide training/support to candidates interested in a variety of bench research projects. In the past, she has trained individuals at different levels of training on a variety of topics including: cloning, analysis of promoter function, generation of recombinant viruses, use of recombinant viruses in evaluating immune response/retinal cell differentiation, use of viral vectors for retinal gene therapy, approaches for blocking retinal neovascularization, generation of animal models for retinal disease, identification of mutations which cause retinal disease, methods with which to measure visual behavior in small and large animals, pathogenetic basis of retinal disease. Dr. Bennett would tailor a bench science-training program to accommodate the needs/desires of a trainee interested in retinal disease. In addition to the hands-on bench research training, she would advise the candidate on how to present the research findings in both manuscript format and lecture format. Dr. Bennett encourages trainees to attend local and international research meetings to share research results. On a local level, trainees attend the weekly Bennett lab meeting, the weekly research meeting at the F.M. Kirby Center for Molecular Ophthalmology, the University of Pennsylvania gene therapy trainee presentation seminar series, and numerous lectures and retreats offered by a number of institutes/ centers at Penn (including the Cell and Molecular Biology and the Neuroscience graduate groups, and the Institute of Neuroscience).

Artur Cideciyan, PhD

The Phototransduction and Visual Cycle Laboratory aims to understand the in vivo function of specific molecules expressed in the human retina. Aims are achieved through non-invasive measurement and quantitative analysis of visual function and structure in patients with hereditary retinopathies caused by known molecular defects. Knowledge obtained from such retinopathies is used to glean molecular foundations of normal human vision. Studies performed in parallel with similar experimental methods in animal models are used to determine the correspondence between the models and the patients, and potential therapeutic strategies are tested as appropriate. Research methods include state-of-the-art commercial equipment, custom developed equipment, mathematical modeling and software development. Dr. Cideciyan is available to mentor candidates in quantitative non-invasive methods as applied to patient-oriented research. His projects on specific irregularities of the visual system of patients and animals with specific mutations lend themselves well to having a K12 trainee take responsibility for a well-defined project for which the trainee would have prime responsibility while working in a laboratory environment with a number of ongoing projects in various states of development.

Samuel Jacobson, MD, PhD

The Center for Hereditary Retinal Degenerations, directed by Dr. Jacobson, has both clinical and research activities aimed at understanding the underlying mechanisms of human genetic human retinal degenerative diseases. Patients are evaluated clinically and evaluations are complemented by psychophysical, electrophysiological and retinal imaging studies. Extensive scientific interaction with other laboratories throughout the world has led to discoveries of the molecular bases and disease expression in a host of retinal degenerations. Clarity of mechanism has occurred, for example, in Leber congenital amaurosis, retinitis pigmentosa, cone-rod dystrophy, maculopathy, the enhanced S-cone syndrome, Usher syndrome and the Bardet-Biedl syndrome. A major collaboration among three academic institutions recently led to the first human trial of gene replacement therapy for one molecular subtype of Leber congenital amaurosis and Dr. Jacobson is the clinical principal investigator of this research. At the Center, there are ongoing pilot studies of nutritional and medical intervention in certain inherited retinal degenerations. Preclinical experiments are also performed in genetically engineered and naturally occurring rodent and large animal models of the human retinal degenerative diseases with the goal of translating these results from the laboratory to the clinical population served by the Center. There are many opportunities for K12 trainees to identify and extend research projects associated with the main goals of the Center.

Maureen Maguire, PhD

The Center for Preventive Ophthalmology and Biostatistics (CPOB), directed by Dr. Maguire, leads and collaborates in clinical research through study design, protocol development, comprehensive data management, cutting-edge interpretation of fundus images, statistical analysis, and interpretation of data. The Center is actively involved in clinical research projects ranging from small, single investigator studies to large, multi-center, multi-disciplinary clinical research studies. The Complications of Age-related Macular Degeneration Prevention Trial (CAPT) is an NEI-sponsored, randomized, clinical trial involving 23 clinical centers nationwide, and 1000 patients. The trial is evaluating laser treatment among patients at high risk of developing severe loss of vision from age-related macular degeneration. Both Coordinating Center and the Fundus Photograph Reading Center are part of the CPOB. The Vision in Preschoolers Study (VIP) is an NEI-sponsored multi-center study to evaluate the accuracy of traditional and newly developed screening tests for detecting amblyopia, strabismus, and significant refractive error in preschool children. Through a series of evaluation cycles, nearly 10,000 children will be tested through five clinical centers nationwide over a period of 5 to 6 years. The Coordinating Center for VIP is part of CPOB. Through the Biostatistics Module of the Penn Core Grant for Vision Research, CPOB methodologists (statisticians and epidemiologists) and data management staff consult with clinical and basic scientists within the Department of Ophthalmology and in other Penn departments (Neurology, Neuroscience, Physiology) on study design and data analysis and interpretation.

Multicenter clinical investigations often engender ancillary research studies that would provide research topics for K12 trainees. The growing archive of color stereoscopic and fluorescein angiographic images of clinically well-characterized patients with various stages of age-related macular degeneration offer opportunities in the areas of natural history, correlations of physiologic changes with visual function, and computer-assisted analysis of images. In addition, as new instrumentation and approaches to vision screening are developed, studies of accuracy, reliability, and responsiveness to change will be needed. Dr. Maguire is currently working with investigators within the Department of Ophthalmology as well as with investigators from other institutions (Johns Hopkins University, Jefferson Medical College, Beth Israel Hospital) on plans for large scale clinical research studies in low vision rehabilitation, the interplay of loss of vision from AMD and depression, the treatment of patients with ocular myasthenia gravis, and the predictive value of features of the retinal vasculature in the progression of renal disease and development of cardiovascular events in patients with chronic renal insufficiency. Depending on the time to maturation of these plans, K12 trainees may take major roles in working with collaborators in designing the execution, analysis, and interpretation of these studies. Finally, trainees will be able to observe and participate in the data monitoring activities and administrative structures of multi-center, interdisciplinary studies.

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