The Knights Templar Eye Foundation is dedicated to funding research into the prevention and treatment of sight threatening diseases in children. Each year, the foundation invites proposals for funding of research related to pediatric ocular disorders. Dr. Sumanth Manohar, a postdoctoral research scholar working in the lab of Dr. Ann Morris in UK’s Department of Biology, was one of 25 scientists selected to receive this funding in 2023-2024.
Manohar will be investigating the function of the CHD7 gene during retinal development and how mutations in CHD7 cause the ocular complications associated with CHARGE syndrome. Manohar hopes to elucidate the mechanisms of action of CHD7 in the retina using the zebrafish model; the results of this work could eventually lead to better therapeutic approaches for the vision problems of individuals with CHARGE syndrome.
“Dr. Manohar is an outstanding scientist, who approaches his research with an impressive level of rigor and scholarship," Morris said. "Dr. Manohar’s research will address an important gap in our understanding of CHD7 function and how it contributes to pathogenesis of CHARGE syndrome. I am thrilled that Dr. Manohar has received funding from the Knights Templar Eye Foundation to pursue this important work.”
A summary of the proposed project is described below.
CHARGE syndrome is a multi-syndromic disorder that is a significant cause of pediatric vision impairment. Mutations in the chromatin remodeling factor CHD7 are the major cause of this disease. Although pathogenic variants of CHD7 are strongly associated with ocular complications, the pathogenetic mechanisms underlying vision loss are not thoroughly understood. Our lab has been investigating the function of CHD7 during retinal development using chd7 mutant zebrafish, which demonstrate similar phenotypes to those observed in individuals with CHARGE syndrome. We observed that loss of CHD7 causes a reduction in the number of retinal cone photoreceptors as well as abnormal photoreceptor outer segments. Other studies have also shown a reduction in the number of ganglion cells in chd7 morphant zebrafish embryos. These results suggest that CHD7 plays a critical role in retinal cell type differentiation, particularly of the ganglion and photoreceptor cells. The goal of this proposal is to determine how CHD7 functions to regulate cell type differentiation in the retina, by utilizing single cell transcriptomic and chromatin binding assays in the zebrafish model. Results of these experiments will provide critical information on how CHD7 regulates retinal development, which could lead to development of new therapeutic approaches for the vision impairment associated with CHARGE syndrome.