Research Overview
Dr. Deng's laboratory studies how mutations in the genes encoding the long- and middle-wavelength cone opsins (OPN1LW/OPN1MW) disrupt the structure and function of cone photoreceptors, and how this damage can be prevented or reversed through gene therapy. Our primary disease model is Blue Cone Monochromacy (BCM), a rare X-linked disorder caused by deletions or point mutations in this gene cluster. BCM serves both as a clinically important target for therapy and as a window into the broader biology of how cone photoreceptors are maintained and how cone opsin proteins are trafficked within the cell.
Gene Therapy for Blue Cone Monochromacy
Using two genetically distinct mouse models that together capture the two major classes of human BCM mutation — a knock-in line carrying a common missense mutation and a double-knockout line modeling large gene deletions — we have defined how these mutations damage cone cells and developed AAV-based gene therapy that restores cone structure and function across both mutation types. This body of work underlies an ongoing collaboration with Blue Cone monochromacy Families Foundation (https://www.blueconemonochromacy.org/blueconemonochromacy/) to advance AAV gene therapy program toward clinical application.
Next-Generation Gene Editing
We are also interested in applying the most advanced gene-editing tools to treat inherited retinal disorders, including cases caused by toxic, dominant-negative mutations that conventional gene supplementation therapy cannot correct. Our lab is developing compact, all-in-one AAV CRISPR platforms with the goal of directly correcting or silencing disease-causing mutations, such as our toxic cone opsin mutants. These systems are designed to fit within the tight packaging limits of a single AAV vector, a major hurdle for delivering CRISPR-based therapies.
Understanding Cone Opsin Trafficking
A newer direction in the lab in collaboration with Dr. Robichaux, investigates how cone opsin protein is trafficked from its site of synthesis to the light-sensing outer segment — a fundamental cell biology
question with direct relevance to disease. We have generated novel mouse lines that allow us to visualize
this trafficking process and identify cone opsin trafficking partners, opening a previously understudied
area of cone cell biology.