Research
Retinal Degeneration & Gene Therapy
Retinitis Pigmentosa (RP) is a wide array of progressive debilitating visual disorders caused by one of many possible genetic mutations, which leads to photoreceptor degeneration and ultimately loss of vision. While AAV-mediated gene replacement therapies have recently ameliorated a small subset of patients with a specific genetic mutation, a comprehensive, mutation-independent treatment is currently unavailable. Most genes mutated in RP are expressed solely in rods, and the mutations lead to rod degeneration and night blindness. Unfortunately, rod death is followed by secondary cone degeneration, which is ultimately responsible for decreased quality of life. Our lab’s goal is to develop novel gene therapies to prolong cone survival that can be used for all patients with RP.
Technology Development
Our lab aims to develop new molecular tools and technologies to facilitate the dissection of molecular mechanisms underlying retinal degeneration and beyond. The retina is a great testing ground for novel molecular tools, especially in vivo, because of its accessibility and comprehensive classification of known cell classes and subtypes. Previously, we developed Probe-Seq and FIN-Seq, which allow easy transcriptional profiling of specific cell types without the need for a promoter. As we extend Probe-Seq beyond transcriptional profiling, we will concurrently explore new ways to manipulate and profile the retina.
Photoreceptor Outer Segment Development & Regeneration
The outer segment is a unique and crucial structural component of photoreceptors that house the machinery to detect light. Therefore, proper functioning of rod and cone photoreceptors rely on working outer segments. During retinal degeneration, cones lose their outer segments even though the cell bodies and downstream connections remain. In addition to pursuing strategies to prolong cone survival (see above), we believe that regenerating cone outer segments will be necessary for functional gene therapy. We hope that, by understanding how the outer segments develop, we can understand the molecular logic to induce regeneration of outer segments.