Research conducted by Yichen Ge, PhD, left, and Xiuqian Mu, MD, PhD, is attempting to identify the proteins that interact with the transcription factor Atoh7 during retinal ganglion cell development.
Research Focuses on Retinal Ganglion Cell Development
By Dirk Hoffman
Published May 12, 2026
Xiuqian Mu, MD, PhD, professor of ophthalmology at the Jacobs School of Medicine and Biomedical Sciences, has received additional funding from the National Eye Institute for his research on retinal development, which could help develop strategies to treat degenerative retinal diseases such as glaucoma.
The National Institutes of Health R21 grant, titled “Atoh7 Interacting Proteins Involved in Retinal Ganglion Cell Genesis,” provides $440,275 in funding over two years.
“This study falls into the general field of my lab’s research on the molecular and genetic mechanisms controlling retina development, but this is a completely new direction using a recently developed technology called proximity-dependent labeling,” Mu says. “This is an exploratory project, which fits the R21 funding mechanism perfectly.”
Utilizing Powerful New Biochemical Technique
Proximity-dependent labeling is a powerful biochemical technique used to identify biomolecules, typically proteins or RNA, that are physically close to a specific “bait” protein within a living cell.
This project aims to understand how Atoh7, a key regulator controlling the developmental genesis of retinal ganglion cells, interacts with other protein partners to carry out its function.
Mu’s lab studies transcription factors, which are proteins that control which genes are activated at specific biological processes. Mu conducts his research at the Ross Eye Institute.
The transcription factor being studied in this project — Atoh7 — controls the activation of genes required for the generation of a kind of retinal cells, retinal ganglion cells, during retinal development, Mu explains.
“Retinal ganglion cells (RGCs) are critical for vision since they relay the visual signals to the brain via the optic nerve so that we can perceive what we see,” Mu adds. “Although the importance of Atoh7 in retinal ganglion cell generation is well established, how it carries out its function is still not completely known.”
One possibility is that it does so by interacting with other proteins.
“This is our central hypothesis,” Mu says. “Our objective is to identify the proteins that interact with Atoh7 using a recently developed technique called proximity dependent biotinylation.”
Seeking Treatments for Retinal Diseases
The study’s specific aims are:
- to identify proteins interacting with Atoh7 in the developing retina and characterize the specificity of the interactions
- to investigate the function of Atoh7 interacting proteins in RGC genesis
“The first aim, which is the foundation of the project, would traditionally be achieved through genetic or biochemical techniques, but we cannot use those techniques because they are either not sensitive enough or require a large amount of material which we cannot obtain,” Mu says.
To overcome this, the researchers are proposing to use proximity dependent biotinylation. In this technique, the protein of interest, Atoh7 in this case, is fused to a modified bacterial enzyme named BioID2 which is a biotin ligase.
“This fusion protein is capable of tagging the proteins in its close proximity with a small molecule called biotin. So, proteins interacting with Atoh7 will be tagged with biotin by the Atoh7-BioID2 protein,” Mu says.
“This biotin tag will enable these proteins to be purified using a standard affinity purification procedure,” he adds. “The purified proteins can then be identified by mass spectrometry.”
Once that is achieved, the researchers in the second aim will further characterize the nature of these proteins’ interactions with Atoh7 and their functions in collaborating with Atoh7 to promote retinal ganglion cell genesis. Mu says this will be accomplished through a combined approach of biochemistry, molecular biology and genetics.
“In our proposal, we provided very strong preliminary data to demonstrate the feasibility of this approach and obtained very favorable critiques from the review panel,” Mu says.
Mu says the study will lead to a better understanding of the developmental process of RGCs, which are implicated in multiple retinal diseases, and help develop therapeutic strategies to treat relevant retinal diseases such as glaucoma.
Yichen Ge, PhD, a research scientist in Mu’s lab, is a major participant in the project.
“He is the major person who has generated all the preliminary data,” Mu says. “He will continue to work on the project to achieve the proposed aims.”