School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Dr. Le Zhang, Assistant Professor of Neurology and of Neuroscience, School of Medicine, Yale University
Talk Title: Immune network dysregulation of the central nervous system in Parkinson's disease

Date: 26 June 2025 (Thursday)
Time: 4:00 pm – 5:00 pm
Venue: Seminar Room 1B, G/F, The HKJC Bldg for Interdisciplinary Research, 5 Sassoon Road
Host: Professor Zhongjun Zhou

Biography

Dr. Le Zhang is an Assistant Professor of Neurology and of Neuroscience at the Yale University. Her research focuses on the immune responses of the central nervous system in neurodegenerative diseases, including Parkinson’s disease and Alzheimer’s disease. By integrating cutting-edge single cell technologies, human research, and mouse genetics, her lab aims to elucidate the body to brain immune axis in both health and disease.

Dr. Zhang earned her B.S. in Biological Sciences from Beijing University in 2004 and her Ph.D. in Molecular Biology and Biochemistry from the University of Hong Kong in 2010, where she studied epigenetic regulation in aging and senescence under the mentorship of Dr. Zhongjun Zhou. She continued her training in epigenetics and neuroscience as a postdoctoral fellow with Dr. Zhaolan Zhou at the University of Pennsylvania and as a research fellow with Dr. Jordan Kreidberg at Harvard Medical School. After a short journey at Pfizer in the R&D of neuroscience, Dr. Zhang joined the Yale University School of Medicine leading single cell research in neuroimmunology and neurological disorders, and started her current position as Assistant Professor in the Departments of Neurology and Department of Neuroscience in 2020. Dr. Zhang is a recipient of NIH NIDA Avenir Award for innovative research and NIH Blueprint for Neuroscience Interoception Research Initiative Early-Stage Investigator Award. Her work has been published in leading journals, including Nature, Science Translational Medicine, Nature Neuroscience, Nature Communications, and Science Immunology, among others.

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by dopaminergic neuron loss and α-synuclein aggregation. REM sleep behavior disorder (RBD), a prodromal α-synucleinopathy, offers a window into early PD pathogenesis. To investigate neuroimmune interactions in PD, we integrated single cell genomics, proteomics, and microbiome analyses across brain, CSF, blood, and gut. In postmortem brains, we observed cell type–specific transcriptional changes, including elevated brain-resident T cells and reduced neuron-astrocyte interactions. CSF and blood single cell profiling from 84 individuals revealed CSF pleocytosis in RBD, with expansion of microglia-like macrophages expressing JAK-STAT and TNFα signaling, which is distinct from autoimmune MS. These findings highlight a myeloid-driven TNFα-mediated neuroinflammatory process in prodromal PD. This integrative approach reveals early immune dysregulation as a key driver of PD pathogenesis and establishes a foundation for targeting immune responses in the central nervous system as a therapeutic strategy in prodromal and early PD.

All are welcome.