Understanding Cellular Vulnerability and Adaptation in the Brain

• How do cells choose their identities during development, and why do some cells remain resilient while others become vulnerable during disease?

• The Kim Group investigates how neuronal and immune cell states emerge, adapt, and fail in the brain. Our work focuses on the regulatory logic that governs cellular identity, metabolic adaptation, and vulnerability across development, ageing, and neurodegenerative disease.

• By combining large-scale single-cell genomics, spatial molecular imaging, and functional perturbation in mouse models, we aim to understand how gene regulatory programs and metabolic constraints shape brain cell behaviour in both healthy and diseased states.

Research Themes

• Microglial Metabolism and Immune Control in Neurodegeneration

Microglia are the brain’s resident immune cells and play a central role in determining whether neural circuits remain stable or deteriorate during ageing and Alzheimer’s disease. Our research investigates how metabolic rewiring, lipid handling, and inflammatory signalling shape microglial states during disease progression. In particular, we study how disruptions in cellular metabolism and lysosomal function alter immune responses and contribute to neuronal vulnerability. By mapping microglial trajectories across disease models and human datasets, we aim to identify molecular pathways that regulate immune restraint and may represent new therapeutic targets.

• Developmental Programming of Hypothalamic Circuits

The hypothalamus regulates fundamental physiological and behavioural processes, including metabolism, stress responses, and energy balance. Despite its importance, the molecular mechanisms that generate its diverse neuronal populations remain poorly understood. We study how transcriptional and chromatin regulatory networks guide hypothalamic cell fate specification during development and how these programs influence long-term cellular vulnerability. By integrating developmental atlases with disease models, our work seeks to uncover how early regulatory programs shape the resilience or susceptibility of specific neuronal populations later in life.

Methodological Platforms

Our research integrates computational biology, molecular neurobiology, and advanced spatial imaging to investigate cell states across scales.

• Single-Cell and Multi-omic Analysis

  • We generate and analyse large-scale datasets using:

    • single-cell RNA-sequencing

    • single-cell chromatin accessibility profiling (scATAC-seq)

    • gene regulatory network inference

    • spatial transcriptomic integration

  • These approaches allow us to reconstruct developmental trajectories and disease-associated cellular states across hundreds of thousands of cells.

• Spatial Molecular Imaging

  • To resolve cellular states within intact tissue, we develop and apply multiplexed RNA imaging methods, including our platform for whole-brain 3D transcriptomic mapping.

    • These methods enable spatially resolved analysis of gene expression across large cleared tissues and allow us to link molecular programs to anatomical circuits.

• Functional Perturbation in Model Systems

  • To test causal mechanisms, we combine molecular imaging and genomics with experimental manipulation in cellular and mouse models, including:

    • CRISPR-based gene perturbation

    • transgenic disease models

    • in vitro functional assays of microglial and neuronal states

  • These approaches allow us to directly test how regulatory and metabolic programs influence cellular behaviour in the brain.

Collaboration and Opportunities

We welcome collaborations across neuroscience, genomics, metabolism, and computational biology.

Prospective PhD students, postdoctoral fellows, and collaborators interested in cellular vulnerability, neuroimmune interactions, and spatial transcriptomics are encouraged to contact us.