Gary (Hin-Fai) Yam, PhD

  • Research Associate Professor of Ophthalmology
  • Corneal Regeneration Laboratory
  • University of Pittsburgh School of Medicine

A Conversation With Dr. Yam

Dr. Gary Yam obtained his Ph.D. from The Chinese University of Hong Kong (CUHK), where he studied viral gene integration to nuclear protein scaffold during carcinogenesis. He started his vision research during his post-doctoral training under Prof. Dennis Lam and Prof. C.P. Pang at the Department of Ophthalmology & Visual Sciences, CUHK. He then joined Roth Lab, University of Zurich, Switzerland, as a research scientist and studied chaperone-mediated protein rescue for Fabry’s disease and myocilin-caused primary open-angle glaucoma. His scientific contribution was acknowledged through the prestigious Alfred Vogt Prize presented by the Swiss Ophthalmology Society and a patented method and medication. In 2006, he returned to CUHK as an Assistant Professor, and further explored chaperone-mediated rescue of protein misfolding and mis-trafficking and epigenetic regulation in corneal epithelial differentiation. He received Best Research Awards from Actions For Vision in 2007 and 2009. From 2012 to 2019, he was a Principal Investigator in the Singapore Eye Research Institute. He worked with Prof. Jodhbir S. Mehta to study stromal cell therapy for corneal scarring, scaffold-based tissue engineering, and novel biomaterials as substitutes to rebuild corneas.

Dr. Yam joined the Department of Ophthalmology at the University of Pittsburgh in 2020. His lab (Corneal Regeneration Lab) focuses on developing innovative therapeutic methods to reduce corneal fibrosis and scarring. His pre-clinical work has identified the anti-scarring effects of corneal stromal stem cells (CSSC) mediated by anti-fibrotic cytokines and microRNAs delivered via nanosized microvesicles. He secured funding from the Hillman Foundation and NIH Regenerative Medicine Innovative Project U01 to advance this CSSC approach from bench to bedside for corneal scar management. His lab also developed quality control assays and methods to predict the healing potency of CSSC. Currently, his team is conducting pharmacological-toxicology and GLP validation studies to prepare for FDA-IND applications and clinical trials. Besides, his research has discovered corneal endothelial progenitors that open the avenue of regenerative therapy for corneal endothelial dystrophies.

Personnel in Yam Lab (Corneal Regeneration Lab) (https://ophthalmology.pitt.edu/research/research-laboratories/corneal-re...)
Moira L Geary Lab manager and Senior Research Associate (animal modelling)
Mithun Santra, Ph.D. Post-doctoral Associate
Elizabeth Rubin Student Researcher
Christine Chandran Student Researcher

Academic Appointments

  • 2020-Present Research Associate Professor, Ophthalmology, University of Pittsburgh School of Medicine
  • 2021-Present Scientist, McGowan Institute for Regenerative Medicine, Pittsburgh
  • 2012-2019 Principal Investigator, Singapore Eye Research Institute
  • 2006-2012 Assistant Professor, Ophthalmology & Visual Sciences, Chinese University of Hong Kong
     

Education & Training

  • Postdoctoral Fellow – Ophthalmology & Visual Sciences, CUHK, Hong Kong SAR
  • Postdoctoral Fellow – Div Cell & Molecular Pathology, Department of Pathology, University of Zurich, Switzerland

Representative Publications

  • Yam GH, Pi S, Du Y, Mehta JS. Posterior Corneoscleral Limbus: Architecture, Stem Cells, and Clinical Implications. Prog Retin Eye Res 2023. doi: 10.1016/j.preteyeres.2023.101192
  • Yam GH, Yang TB, Geary ML, et al. Human corneal stromal stem cells express anti-fibrotic microRNA-29a and 381-5p – a robust cell selection tool for stem cell therapy of corneal scarring. J Adv Res 2023. doi: 10.1016/j.jare.2022.05.008.
  • Santra M, Liu YC, Jhanji V, Yam GH. Review: Human SMILE-Derived Stromal Lenticule Scaffold for Regenerative Therapy: Int J Mol Sci 2022. doi: 10.3390/ijms23147967.
  • Yam GH, Bandeira F, Liu YC, et al. Effect of corneal stromal lenticule customization on neurite distribution and excitatory property. J Adv Res 2022. doi: 10.1016/j.jare.2021.09.004.
  • Yam GHF, Riau AK, Funderburgh ML, Mehta JS, Jhanji V. Review: Keratocyte biology. Exp Eye Res 2020. doi: 10.1016/j.exer.2020.108062.
  • Yam GH, Seah XY, Yusoff NZ, et al. Characterization of human transition zone reveals a putative progenitor-enriched niche of corneal endothelium. Cells 2019. doi: 10.3390/cells8101244.
  • Yam GH, Fuest M, Yusoff NZ, et al. Safety and feasibility of intrastromal injection of cultivated human corneal stromal keratocytes as cell-based therapy for corneal opacities. Invest Ophthalmol Vis Sci 2018. doi: 10.1167/iovs.17-23575.
  • Yam GH, Peh GS, Singhal S, Goh BT, Mehta JS. Review: Dental stem cells: a future asset of ocular cell therapy. Expert Rev Mol Med 2015. doi: 10.1017/erm.2015.16. 
  • Yam GH, Gaplovska-Kysela K, Zuber Ch, Roth J. Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin and rescues cells from endoplasmic reticulum stress and apoptosis. Invest Ophthalmol Vis Sci 2007. doi: 10.1167/iovs.06-0943
  • Yam GH, Gaplovska-Kysela K, Zuber Ch, Roth J. Aggregated myocilin induces Russell bodies and causes apoptosis: implications for the pathogenesis of myocilin-caused primary open-angle glaucoma. Am J Pathol 2007. doi: 10.2353/ajpath.2007.060806

Full list https://www.ncbi.nlm.nih.gov/myncbi/gary.yam.1/bibliography/public/ 

Research Interests

Ocular cell biology and tissue engineering, corneal stem cells (epithelial, stromal and endothelial), cell-based and cell-free therapies, extracellular vesicles/exosomes, epigenetic regulation (microRNAs), ocular genetics, protein biosynthesis and trafficking, protein quality control, protein misfolding, endoplasmic reticulum stress, chaperone-assisted protein rescue.

The Corneal Regeneration laboratory 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 significant biological barrier to infection. Globally, millions of patients have corneal opacification due to disease or trauma, hence vision loss. Our work focuses on the biological processes that produce and maintain the unique tissue of corneal stroma as well as the pathological changes that occur during injury, wound healing, scarring and diseases. We explore new designs to reverse the scarring process or replace the scarred cornea with bioengineered corneal tissue. Our lab has reported the use of stromal keratocytes and stromal stem cells to restore corneal transparency. These cell-based treatments produce tissue identical to that of the transparent corneal stromal tissue in animal models of corneal injury. We are developing GMP compliant Standard Operating Procedure for clinical trials in patients with corneal scarring. We are also actively investigating the mechanism by which the stem cells induce tissue regeneration, including exosomes, cytokines, and microRNAs.

Research Grants

National Institute of Health RMIP U01 EY035252: 9/2023-9/2025  
“A Cell Therapy Program with Scale-up cGMP Manufacturing of Human Corneal Stromal Stem Cells” 
 
Hillman Foundation: 7/2021-6/2025 
“Stromal cell regeneration therapy for corneal scarring – Corneal Regeneration Project to Clinical Trials” 
 
Immune Transplant and Therapy Center, UPMC: 8/2020-5/2023 
“Epigenetic regulation to immunosenescence and inflammatory responses in aging corneas” 
 
Eye Bank Association America (High Impact Research Grant): 12/2020-5/2022 
“Cell-based therapies for corneal diseases”