The William C. Frayer Professorship of Ophthalmology
The chair was established in l995 by gifts from many patients, friends, and colleagues of Professor Emeritus William C. Frayer, MD (1921–2012). Widely respected for his concern for his patients, his advances in ophthalmic pathology, and his dedication to his students, Dr. Frayer helped to found the Scheie Eye Institute and served as Professor of Ophthalmology for more than 20 years.
Dr. Frayer began his medical career as Captain in the U.S. Army from 1946 to 1948. He found his assignment in ophthalmology to be highly satisfying and subsequently completed a dual residency in ophthalmology and pathology at the Perelman School of Medicine. He joined the faculty in 1952.
He left Penn in 1964, but returned in 1972 to help launch the Scheie Eye Institute. At Scheie, Dr. Frayer was the longtime Director of the Ophthalmic Pathology Laboratory, which now bears his name. On two separate occasions, he served as interim Chair of the Institute. Dr. Frayer was awarded emeritus status in 1991. During his retirement, he wrote the memoir An Ophthalmic Journey: 50 Years at the University of Pennsylvania and continued to mentor faculty and residents at the Scheie Eye Institute.
Current Chairholder:
Dwight E. Stambolian, MD, PhD
Dr. Stambolian earned his BA from Lycoming College and his MD from SUNY Downstate. He subsequently pursued a PhD in genetics at the University of Pennsylvania. He is currently a standing faculty member at the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center, as well as a member of Penn's Institute for Human Gene Therapy. Dr. Stambolian's research is concentrated on genome-wide association studies of age-related macular degeneration (AMD), targeted sequencing and genetics for AMD in African Americans and Amish populations, and other glaucoma, refractive error, and microphthalmia topics.
Dr. Stambolian's laboratory employs cutting-edge DNA sequencing technology to determine the reasons for the reduced severity of AMD in African Americans. His current research involves the use of targeted next-generation sequencing to identify protective haplotypes that may account for the resistance to AMD development in African Americans. He has compiled a substantial cohort of African American cases and controls. These protective single nucleotide polymorphisms (SNP) could potentially serve as new drug targets if they are identified.
Dr. Stambolian has achieved significant success in the identification of susceptibility genes for AMD through genome-wide association studies (GWAS). Understanding the expression disparities between eyes with AMD and eyes that are normal is the subsequent objective. Dr. Stambolian has compiled a collection of postmortem eyes with and without AMD in order to identify differential expression between normal and AMD eyes. RNA and DNA have been extracted from these eyes for the purpose of genotyping and RNA sequencing. His underlying hypothesis is that AMD is predisposed to a defect in alternative splicing or a difference in normal transcript expression between normal and AMD eyes. The SplicePL algorithm, which was developed in the laboratory, is being used to analyze the RNA-Sequencing data for alternative splicing defects and expression differences. Expression will also be correlated with known AMD risk SNPs to evaluate the potential of SNPs to influence expression.
The genetics of AMD have been extensively investigated in unrelated Caucasian case-control cohorts. Nevertheless, there has been a dearth of research on the identification of genes within families. Dr. Stambolian has conducted screenings for a variety of eye diseases, including AMD, on 3000 Amish individuals over the age of 50 residing in Lancaster County, PA. In addition to the donation of a blood sample, each participant who visited the Amish clinic underwent a comprehensive eye examination, completed an epidemiology questionnaire, and had their fundus photographed. Currently, his Amish cohort is comprised of over 750 nuclear families and possesses an immense capacity to detect rare variants. He is currently in the process of preparing to conduct whole exome sequencing in specific families to identify rare variants in AMD. The general population will potentially be impacted by the discovery of rare AMD variants with a significant effect.
Dr. Stambolian's laboratory is currently leading an international consortium to identify the genes responsible for refractive error through next-generation sequencing and GWAS. They are currently in the process of elucidating the mechanisms by which these significant GWAS SNPs contribute to the development of refractive error, having completed GWAS on 7000 individuals. His team employs bioinformatic tools to characterize the function of these SNPS and will transition to functional studies in zebrafish once bioinformatic tools have been exhausted. Furthermore, he has amassed DNA from vast families that transmit myopia and is in the process of conducting whole exome sequencing to identify rare variants in these families.
Dr. Stambolian has also developed a system to evaluate the refractive error phenotype in zebrafish embryos. As a validation of the GWAS hits he has identified, current experiments involve the overexpression and knockdown of a variety of potential refractive error genes. The mutants will be subjected to RNA-Sequencing following the validation of their results in a zebrafish model. This will establish a foundation for a systems biology approach to the understanding of refractive error.
Dr. Stambolian work has been critical to the development of mouse models for microphthalmia. The causative locus was refined to a 1.3Mb region on mouse Chromosome 4, which contains five genes, through genetic mapping. His laboratory is currently conducting additional molecular characterization to identify the founder mutation that is responsible for the microphthalmic phenotype.
Previous Chairholders:
- Richard A. Stone, MD
- Samuel Jacobson, MD, PhD