Xian-Jie Yang Laboratory
Retinal Development and Gene Therapy
Uncovering the mechanisms of retinal development and finding new therapeutic approaches
Xian-Jie Yang, Ph.D.
Professor
Department of Ophthalmology
Director, Molecular Biology and Gene Delivery Core
Jules Stein Eye Institute
Regulatory Mechanisms Involved in Retinal Development and Repair
Research of the Yang laboratory aims at understanding mechanisms regulating retinal development and maintenance. We study how intrinsic cell signaling events influence progenitor cell proliferation and neuronal fate commitment during retinal neurogenesis, and how exogenously applied growth factors affect neuronal survival under disease conditions. We also use human pluripotent stem cell-derived retinal organoids and neurons to establish disease models for inherited optic neuropathy and to facilitate treatment development.
I. We are using molecular genetic approaches to addresses mechanisms of neuroprotection:
- Which cellular metabolic pathways contribute to neuronal maintenance?
- How does retinal degeneration alter mitochondrial morphology and function?
- What cellular signaling events are triggered by trophic factors to enhance neuronal viability?
- How to elicit retinal intrinsic neuroprotective potential?
Outcomes of the research will provide much needed insight for ongoing clinical trials aimed at treating retinal degenerative diseases.
II. We are using stem cell technology and virus-mediated gene delivery to study human retinal development, elucidate disease mechanism of inherited optic neuropathy, and develop effective therapies:
- How does neurogenic transcription factors regulate early retinal neuronal fates?
- Does mitochondrial deficiency affect human retinogenesis?
- What are the disease phenotypes of optic neuropathy in stem cell-based models?
- Can viral vector-mediated gene therapy or metabolic modulation attenuate inherited retinal degeneration?
These studies will provide more efficient methodology to produce human retinal neurons and new knowledge regarding human retinal development. Furthermore, stem cell-based human optic neuropathy disease models will be a valuable testing platform to evaluate the efficacy of novel treatment strategy prior to clinical trials.
Recent Publications
Derivation and Characterization of Isogenic OPA1 Mutant and Control Human Pluripotent Stem Cell Lines
Katherine A. Pohl, Xiangmei Zhang, Johnny Jeonghyun Ji, Linsey Stiles, Alfredo A. Sadun, Xian-Jie Yang
Cells (2025)
View Publication