Research Description

One of the fundamental questions common to all of the neurodegenerative diseases is why a particular disease targets specific neuronal populations? The Fu laboratory research focuses on understanding which subtypes of neurons are vulnerable to tau pathology in early Alzheimer’s disease (AD) and other tauopathies as well as the molecular and cellular mechanisms underlying the selective neuronal vulnerability. In particular, they are interested in investigating the role of cell-autonomous (neurons) versus cell non-autonomous (microglia, astrocytes and oligodendrocytes) effects in selective vulnerability to proteinopathies in neurodegenerative diseases.

Utilizing AD-like mouse models, human postmortem brains, and human iPSC-derived neural organoid model with AD or FTD risk genes, the team reveals cell-type-specific gene signatures and biological pathways are correlated with AD pathology, and cell-cell communications (i.e., neuron-glia) are altered in AD. Several hub genes have been found to regulate tau degradation and clearance in tau mouse models. The long-term vision of the Fu lab research is to identify and manipulate molecular determinants underpinning selective cellular vulnerability as therapeutic targets that will complement existing strategies for the treatment of AD and other neurodegenerative diseases.