Dr. Zhao

Dr. Zhao’s project will study the important role of RNA m6A modification on the regulation of Mapt (Tau) mRNA metabolism in Pick’s disease and tauopathy. In this project, Dr. Zhao will study how the neuronal m6A reduction in Pick’s disease brains contributes to abnormal Tau splicing and accumulation and explore the pathological consequences of dysregulated m6A modification in Tau-related neurodegeneration in AD and related dementia.

This new R03 was awarded shortly after Dr. Zhao received a 2-year R21 grant with $442k funding from NIA (2024-2026), which actively investigates how reduced neuronal m6A modification leads to abnormal amyloid-β accumulation and AD pathology by modulating abnormal APP metabolism.

Why is this important? Alzheimer’s disease (AD) is one of the major public health problems without a cure. Current treatments are limited and mainly provide symptomatic relief because they are non-specific about the cause of disease. It is believed that a combination of genetics, environmental, and lifestyle factors affects the risk of developing AD through complex transcriptional and translational changes in the gene expression in AD brains. An understanding of these changes will help shift the treatment from symptomatic relief to disease-modifying novel therapies.

We will test how neuronal m6A dysregulation leads to the abnormal mRNA metabolism and disease onset with a focus on the most important disease risk factors, including amyloid-β and Tau in AD; thus, our work could lay the foundation for therapeutic targeting of disease-modifying genes/pathways to cure AD.