Yiqiao Zheng

Program: Molecular Genetics and Genomics

Current advisor: Shiming Chen, PhD

Undergraduate university: Hong Kong Polytechnic University, 2017

Enrollment year: 2017

Research summary
Investigating the molecular mechanisms that regulate photoreceptor development and degeneration.

The Cone-rod homeobox gene (CRX) encodes an otd/Otx paired-like homeodomain (HD) transcription factor (TF), essential for photoreceptor development and survival. CRX regulates the expression of both rod and cone genes. Its regulatory activity depends on HD-DNA interactions as well as interactions with other transcription factors.
Mutations in human CRX are often associated with autosomal dominant blinding diseases. My thesis project aims to decipher how missense mutations in the CRX HD cause severe, early-onset, dominant pathological phenotypes.
I am employing an integrated approach – utilizing high-throughput biochemistry assays to establish quantitative in vitro molecular models which are then applied in understanding the molecular, cellular, and functional deficits in human mutation knock-in mouse models. I envision our findings would not only shed light on the regulatory mechanisms of CRX in photoreceptor biology, but also on other important HD proteins and associated diseases.

Graduate publications
Shepherdson JL, Friedman RZ, Zheng Y, Sun C, Oh IY, Granas DM, Cohen BA, Chen S, White MA. 2024 Pathogenic variants in CRX have distinct cis-regulatory effects on enhancers and silencers in photoreceptors. Genome Res, 34(2):243-55. PMCID: PMC10984388

Zheng Y, Chen S.. 2024 Transcriptional precision in photoreceptor development and diseases – Lessons from 25 years of CRX research. Front Cell Neurosci, 18():1347436. PMCID: PMC10896975

Wang J, Cheng X, Liang Q, Owen LA, Lu J, Zheng Y, Wang M, Chen S, DeAngelis MM, Li Y, Chen R. 2023 Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation. Genome Res, 24(1):269. PMCID: PMC10680294

Zheng Y, Sun C, Zhang X, Ruzycki PA, Chen S. 2023 Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms. Elife, 12():RP87147. PMCID: PMC10645426