Epigenetic Regulation in the Nervous System and Brain Disorders
Welcome to the Yao lab in the Department of Human Genetics at Emory University School of Medicine!
Ongoing research directions:
(1) We are fascinated by the pivotal roles that epigenetic marks, such as DNA 5-hydroxymethylcytosine (5hmC), play in mammalian neurodevelopment and neuronal function, as well as by how the dysregulation of these marks contributes to neurodegenerative (Kuehner et al., 2021) and neuropsychiatric disorders (Ma et al., 2023; Kuehner et al., 2023).
(2) We study the nuclear RNA–DNA hybrid structure, termed R-loop, focusing on its crosstalk with DNA modifications. R-loops have recently gained attention for their essential roles in cellular processes, such as regulating gene expression, maintaining genomic stability, and facilitating DNA repair. Our recent findings reveal previously uncharacterized genomic functions of the nuclear RNA-binding protein TDP-43 in modulating R-loop/5hmC coordination across coding genes, distal regulatory elements, and transposable elements (TEs). This work presents a generalizable molecular mechanism underlying the contribution of proteinopathies to the etiology of neurodegenerative disorders (Hou et al., 2023). We are also investigating the crosstalk between DNA modifications and R-loops in human early brain developmental disorders, including Aicardi–Goutières syndrome (AGS) (unpublished) and ataxia-telangiectasia (AT) (Westover et al., 2026), using iPSC-derived neurons from human patients.
(3) We developed two novel computational algorithms, circMeta (Chen et al., 2020; Zhao et al., 2024) and CARP (CircRNA identification using A-tailing RNase R approach and Pseudoreference alignment) (Li et al., 2022) to identify and accurately quantify the genome-wide landscape of a class of non-coding RNAs known as circular RNAs (circRNAs) in mammals. We are investigating the molecular mechanisms underlying the biogenesis and downstream functions of circRNAs in neural and glial development and functions, as well as their unique contributions to Alzheimer’s disease (Wang et al., 2024). We are also interested in other types of non-coding RNAs implicated in human brain diseases (Teng et al., 2023).
Welcome to the Yao lab in the Department of Human Genetics at Emory University School of Medicine!
Ongoing research directions:
(1) We are fascinated by the pivotal roles that epigenetic marks, such as DNA 5-hydroxymethylcytosine (5hmC), play in mammalian neurodevelopment and neuronal function, as well as by how the dysregulation of these marks contributes to neurodegenerative (Kuehner et al., 2021) and neuropsychiatric disorders (Ma et al., 2023; Kuehner et al., 2023).
(2) We study the nuclear RNA–DNA hybrid structure, termed R-loop, focusing on its crosstalk with DNA modifications. R-loops have recently gained attention for their essential roles in cellular processes, such as regulating gene expression, maintaining genomic stability, and facilitating DNA repair. Our recent findings reveal previously uncharacterized genomic functions of the nuclear RNA-binding protein TDP-43 in modulating R-loop/5hmC coordination across coding genes, distal regulatory elements, and transposable elements (TEs). This work presents a generalizable molecular mechanism underlying the contribution of proteinopathies to the etiology of neurodegenerative disorders (Hou et al., 2023). We are also investigating the crosstalk between DNA modifications and R-loops in human early brain developmental disorders, including Aicardi–Goutières syndrome (AGS) (unpublished) and ataxia-telangiectasia (AT) (Westover et al., 2026), using iPSC-derived neurons from human patients.
(3) We developed two novel computational algorithms, circMeta (Chen et al., 2020; Zhao et al., 2024) and CARP (CircRNA identification using A-tailing RNase R approach and Pseudoreference alignment) (Li et al., 2022) to identify and accurately quantify the genome-wide landscape of a class of non-coding RNAs known as circular RNAs (circRNAs) in mammals. We are investigating the molecular mechanisms underlying the biogenesis and downstream functions of circRNAs in neural and glial development and functions, as well as their unique contributions to Alzheimer’s disease (Wang et al., 2024). We are also interested in other types of non-coding RNAs implicated in human brain diseases (Teng et al., 2023).
Yao et al, Nat Rev Neurosci. 2016