Guoyan Zhao, PhD
Assistant Professor, WashU Genetics/WashU Neurology
- Phone: 314-273-9045
- Email: gzhao@nospam.wustl.edu
Transcriptional Regulation and Neurological Disease
Transcriptional regulation largely determines the spatiotemporal specificity and dynamic patterns of gene expression during development and in response to environmental stimuli. We are interested in understanding the molecular mechanisms underlying the precise control of gene expression in the nervous system and how changes in the regulation contribute to neurological diseases. We integrate multiple cutting-edge computational and experimental approaches to study gene transcriptional regulation in the nervous system and how changes in the regulation contribute to chronic pain and neurodegenerative diseases such as Alzheimer disease (AD), Huntington disease (HD), and Parkinson disease (PD). We take snapshots of the regulatory systems using single-cell omics such as single-nucleus RNA sequencing (snRNA-seq) and single-nucleus ATAC sequencing (snATAC-seq). We investigate gene expression and cell-cell interaction in relation with their spatial distributions using single-cell based spatial transcriptomics and spatial proteomics assays such as MERSCOPE and Imaging Mass Cytometry. We analyze postmortem tissues from various disease conditions to identify biomarkers for disease diagnosis and candidate targets for treatment development. We develop computational algorithms to integrate data and generate testable models of gene regulatory pathways to guide our experimental design and test our predictions in model systems. We achieve these goals through collaborations with many laboratories that have already been members of the Hope Center. Our long-term goal is to provide novel insights into the mechanism of disease pathogenesis and new biomarkers and targets for disease diagnosis, prevention and treatment development. Our research will contribute to the mission of the Hope Center in improving the lives of people living with neurological disorders, through collaborative research that aims to discover fundamental mechanisms of neurodegeneration and repair, and translate that new understanding into cures and treatments.