S+S, Fall 2023
Gary Yam, PhD, received a U01 grant from the National Institutes of Health (NIH) based on work from the Hillman-funded Funderburgh Corneal Regeneration Project.
Dr. Yam is a Research Associate Professor of Ophthalmology, Corneal Regeneration Laboratory at the University of Pittsburgh School of Medicine. The Corneal Regeneration Lab focuses on the cornea, an organ that provides a visual portal to the world. The connective tissue of cornea (stroma) is extremely tough and transparent to light. It also presents a strong focusing power to achieve a high level of visual acuity.
Corneal blindness due to corneal scarring affects millions of people worldwide, according to Dr. Yam. Corneal transplantation is effective but has limitations, including the global shortage of donor corneas. His project aims “to establish a new stem cell-based approach to reduce the need of corneal allograft transplantation,” he said. “The scope of work is to validate and confirm procedures to generate Good Manufacturing Practice (GMP) stem cells, verify cell safety, and analyze clinical data towards a cell-based therapy for corneal scarring disorders.”
The Yam Lab and the Corneal Task Force at the Department of Ophthalmology following the innovative work by the late James L. Funderburgh have confirmed the regenerative effects of human corneal stromal stem cells (CSSC) in animal models of corneal scarring. The Hsu Lab and the Immunologic Monitoring and Cellular Products Laboratory (IMCPL) at UPMC Hillman Cancer Center have immense experience in establishing Investigational New Drug Application (IND) manufacturing procedures, quality assurance systems, and documentation to support GMP cell product manufacturing and processing for FDA-registered clinical trials.
The grant will allow these groups to join forces to pave a route to stem cell-based therapy in future clinical trials and clinical applications treating corneal scarring. It supports work targeting three specific aims:
- SA-1 will establish Chemistry and Manufacturing Control (CMC) for GMP grade CSSC for allocation towards IND in FDA. The team will characterize and compare the quality of GMP-raised CSSC and lab-generated cells and establish a complete GMP production protocol.
- SA-2 will elucidate the pharmacological and toxicological effects of GMP-CSSC. The team will study cell safety and efficacy using their established mouse corneal injury model and will determine CSSC distribution, metabolism, absorption, excretion, metabolism, and tumorigenicity.
- SA-3 will run clinical data mining and analysis that will direct future clinical trial design. The team will do retrospective data analysis using corneal keratitis and scarring patient database at the UMPC Eye Centre and obtain statistical data to direct future clinical trial design on patient eligibility and treatment outcome analysis.