Dr. Zhao Sun

Seminar Details

Host: Dr. Bo Zhou

Time: 4:00pm-5:00pm

Location: BICH Rm108

Seminar Abstract

Modeling sporadic neurodegenerative diseases, such as late-onset Alzheimer’s disease (LOAD), which accounts for more than 95% of Alzheimer’s disease (AD) cases, remains a major challenge due to their heterogeneity, complexity, and strong association with aging. Although induced pluripotent stem cell (iPSC)-based models have transformed regenerative medicine and disease modeling, reprogramming to pluripotency erases age-associated molecular signatures and resets cells to an embryonic-like state, limiting their ability to model late-onset disorders. Direct neuronal reprogramming overcomes this limitation by converting patient somatic cells directly into neurons while preserving both the donor’s genetic background and age information. Using this approach, we have successfully modeled Huntington’s disease (HD), familial frontotemporal dementia with tau pathology (FTD-tau), and AD. Directly reprogrammed neurons derived from patient fibroblasts spontaneously recapitulate key disease hallmarks, including huntingtin aggregation (in HD modeling), amyloid-β accumulation (in AD modeling), insoluble seed-competent tau (in AD and FTD-tau modeling), and neurodegeneration (in HD, AD, and FTD-tau modeling), without overexpression of disease-causing gene mutations. Building on this foundation, our lab is currently pursuing three directions: 1) dissecting the age-associated mechanisms linked to AD onset; 2) modeling other neurodegenerative diseases and brain aging through direct neuronal reprogramming. and 3) developing novel reprogramming strategies to generate glial cell types in the brain.