Sangeetha Kandoi, PhD, Awarded All May See Fellowship

Congratulations to Sangeetha Kandoi, PhD, a Postdoctoral Fellow in the Lamba Lab, Department of Ophthalmology, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research on her award of a $50,000 fellowship from All May See Foundation.

Dr. Kandoi’s project entitled – Retinal organoid-based modeling and gene editing for GUCY2D-associated Cone Rod dystrophy – was selected from multiple competitive applications submitted for consideration. Her project was chosen as the most promising proposal.

Significance:
Cone Rod Dystrophy (CRD) is an inherited retinal disease leading to permanent blindness in 1/40,000 individuals globally. Post-mitotic, light-sensing cells in the mammalian retina including cone photoreceptors, providing fine detail and color vision degenerate primarily, followed by the secondary death of rod photoreceptors which provides dim-light vision. Despite the significant advances in clinical and molecular diagnosis of CRD, there is no approved therapy to halt the degeneration or prevent the blindness. Mutations in GUCY2D, the gene encoding retinal guanylate cyclase-1 (RetGC1) is present in the outer segments of photoreceptors and account for 35% of autosomal dominant CRD (CORD6). Under normal circumstances, the RetGC1 restores the light induced photoreceptors (Hyperpolarized) to the dark-adapted (Depolarized) state by replenishing cGMP and allowing the influx of Ca (2+) ions through the opening of the cation channels. This unique biochemical activity of RetGC1 is essential to maintain the physiological function and survival of photoreceptors. However, the missense mutation at the ‘hot-spot’ codon (838) of GUCY2D variants are associated with pathogenic forms of CORD6 via critically altering the RetGC1 activity. Hence, there is a vital need to specifically uncover cone-rod pathophysiology in human CORD6, which, incidentally, can now be assessed using the patient-specific induced pluripotent stem cell (iPSC)-derived retinal organoids. The overall goal of the study is to develop a comprehensively characterized in vitro retinal organoid model of human GUCY2D-CORD6 for understanding the various cone-rod degenerative retinal phenotypes and to correct the associated mutation using the CRISPR/Cas9-gene editing, as a reliable treatment option to restore the catastrophic vision loss. After successful accomplishment of these specific aims, I will have novel GUCY2D-CORD6 variants model-in-a-dish, and a gene edited counterpart cell line that can form the basis for the development of future clinical therapies.

The foundation is excited to support this most worthwhile project and the work of Sangeetha Kandoi, PhD.