Project Overview

• Focus 1: Decoding Microglial States Across Disease

  • Specific Focus: Investigate lipid homeostasis and inflammatory responses in microglia in the context of Alzheimer's Disease and Aging.

• Focus 2: Decoding Neuronal Diversification in the Hypothalamus

  • Specific Focus: Identify intrinsic and extrinsic mechanisms driving selective neuronal vulnerability in Alzheimer's Disease and Aging.

• Focus 3: Turning lead into gold

  • Specific Focus: Understand gene regulatory networks driving the onset of neuropeptides and neurotransmitters.

Methodological Approaches

• Approach 1: Computational Dry Lab

  • Bioinformatics: Employ single-cell RNA and ATAC analysis, along with spatial transcriptomic.

  • Imaging Analysis: Utilize live imaging and multiple single-molecule in situ hybridization techniques.

• Approach 2: In Vitro Experiments

  • Target gene regulatory networks using CRISPR-RNP.

  • Implement live imaging and an in-house multiplex single-molecule in situ hybridization method.

• Approach 3: In Vivo Studies

  • Use transgenic mouse models of Alzheimer's disease.

  • Apply viral targeting, single-cell sequencing, and brain clearing with multiplex single-molecule in situ hybridization.

  • Conduct behavioral analysis to assess impacts.