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Dr. Jimmy Tze Hang LEE
Postdoctoral Fellow & Senior Data Scientist,
Wellcome Sanger Institute,
United Kingdom
Abstract:
Amyotrophic lateral sclerosis (ALS) is a rapidly fatal neurodegenerative disorder characterized by motor impairment. Recent studies have found that cellular vulnerabilities to ALS extend beyond motor neurons to various neuronal and glial populations across the central nervous system. However, whether these cell types exhibit shared or distinct molecular vulnerabilities remains unknown.
In this study, we characterized C9ORF72-related ALS-vulnerable cell types in the human primary motor cortex using single nucleus transcriptomics. First, we created a fine-grained cell atlas of 72 neuronal and glial subtypes, spanning 360,392 single-nucleus transcriptomes from 20 patients with C9HRE ALS and 8 control donors. Second, we applied multicellular factor analysis to characterize cellular and molecular vulnerabilities. We identified a shared ALS gene expression program across multiple excitatory neuronal populations, including layer 5 motor and upper layer intratelencephalic subtypes, as well as PVALB+ and VIP+ interneurons. This vulnerability signature included stress/death and synaptic dysregulation and was validated with spatial transcriptomics data, showing upregulation of genes involved in neuronal apoptotic pathways, while vesicle transport genes were downregulated.
Finally, we examined whether this neuronal vulnerability signature is specific to ALS among neurodegenerative diseases by extending the analysis to an Alzheimer's Disease (AD) dataset. By integrating the SEA-AD dataset, we created a Comprehensive Neurodegenerative Atlas with 1,729,267 single nuclei and identified distinct cellular and molecular patterns specific to ALS.
Bio:
Dr. Jimmy Lee obtained his PhD at the University of Hong Kong. His doctoral research focused on utilizing high-throughput proteomics assays to identify molecular targets that regulate glucose and lipid metabolism in the fat-liver crosstalk. This work led to the discovery of a novel lipocalin, LCN14, in a diabetic mouse model.
Dr. Lee then made a significant career transition into bioinformatics. He joined the Wellcome Sanger Institute in the UK, where he worked with Dr. Martin Hemberg to develop SCfind, a computational platform for multi-omics single-cell data analysis as part of the Human Cell Atlas Project.
In 2021, he joined Dr. Omer Bayraktar’s lab at the Wellcome Sanger Institute as a computational postdoctoral fellow and now serves as a Senior Data Scientist. His research lies at the intersection of machine learning, molecular biology, cellular neuroscience, genetics, and genomics. He focuses on advancing spatial genomics to enhance the understanding of human neurodevelopment and neurological diseases.
Details
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| Venue: |
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Seminar Room 608,
6/F, William MW Mong Block,
LKS Faculty of Medicine,
21 Sassoon Road, Pokfulam,
The University of Hong Kong
All are welcome
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