Email: czou@mail.sioc.ac.cn
Phone: 86-21-68582516
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Principal Investigator, Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
Postdoctoral Fellow, Harvard Medical School, Boston, Massachusetts, US
Ph.D., Ludwig Maximilian University of Munich, Germany
B.S., Southwest University, China
The research in Zou’s lab focuses on understanding the molecular mechanisms underlying pathogenic events of neurodegenerative diseases and developing corresponding treatment strategies in cell-type specific manner. We are mainly focusing on exploring molecular regulators of cell death and neuroinflammation in different types of central nervous system cells and peripheral immune cells.
We have uncovered a novel state of inflammatory microglia in amyotrophic lateral sclerosis, the prevalence of which could be prevented by inhibiting RIPK1 and thus termed as RIPK1-Regulated Inflammatory microglia (RRIMs). The finding of RRIMs helps to elucidate a mechanism by which inhibiting RIPK1 provides therapeutic benefits in ALS.
We have previously shown the selective vulnerability of venular and capillary cerebral endothelial cells to necroptosis in Alzheimer’s disease and identified reduced cerebral endothelial expression of murine N-acetyltransferase 1 that could promote endothelial necroptosis and cause blood brain barrier damage. Our study suggests that targeting peripherally facing cerebral endothelial cells that do not require BBB penetrant therapeutics may provide a strategic target for AD therapies.
One of the keys to successfully treat AD is to identify pathophysiological events in its preclinical stages. We have previously observed impaired dendric spine structural plasticity in preclinical AD and identified multiple underlying molecular mechanisms, including elevated neuroinflammatory cytokines, disturbed extracellular D-serine homeostasis and increased intraneuronal amyloid precursor protein. These studies have provided valuable insights into the biology of dendritic spines and may open avenues for discovery of novel therapeutic targets for AD.
Publications (Updated in July 2022):
1-13
1 Shi, Y. et al. Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO). Nature Neuroscience 25, 317-329 (2022).
2 Li, W. et al. Nuclear RIPK1 promotes chromatin remodeling to mediate inflammatory response. Cell Research, 1-17 (2022).
3 Xu, D., Zou, C. & Yuan, J. Genetic Regulation of RIPK1 and Necroptosis. Annual Review of Genetics 55, 235-263 (2021).
4 Wang, H. et al. NEK1-mediated retromer trafficking promotes blood–brain barrier integrity by regulating glucose metabolism and RIPK1 activation. Nature communications 12, 1-19 (2021).
5 Mifflin, L. et al. A RIPK1-regulated inflammatory microglial state in amyotrophic lateral sclerosis. Proceedings of the National Academy of Sciences 118, e2025102118 (2021).
6 Zou, C. et al. Reduction of mNAT1/hNAT2 Contributes to Cerebral Endothelial Necroptosis and Aβ Accumulation in Alzheimer’s Disease. Cell Reports 33, 108447 (2020).
7 Xu, D. et al. TBK1 suppresses RIPK1-driven apoptosis and inflammation during development and in aging. Cell 174, 1477-1491. e1419 (2018).
8 Ofengeim, D. et al. RIPK1 mediates a disease-associated microglial response in Alzheimer’s disease. Proceedings of the National Academy of Sciences 114, E8788-E8797 (2017).
9 Ofengeim, D., Giagtzoglou, N., Huh, D., Zou, C. & Yuan, J. Single-cell RNA sequencing: unraveling the brain one cell at a time. Trends in molecular medicine 23, 563-576 (2017).
10 Zou, C. et al. Neuroinflammation impairs adaptive structural plasticity of dendritic spines in a preclinical model of Alzheimer’s disease. Acta neuropathologica 131, 235-246 (2016).
11 Zou, C. et al. Amyloid precursor protein maintains constitutive and adaptive plasticity of dendritic spines in adult brain by regulating D‐serine homeostasis. The EMBO journal 35, 2213-2222 (2016).
12 Zou, C. et al. Intraneuronal APP and extracellular Aβ independently cause dendritic spine pathology in transgenic mouse models of Alzheimer’s disease. Acta neuropathologica 129, 909-920 (2015).
13 Dorostkar, M. M., Zou, C., Blazquez-Llorca, L. & Herms, J. Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities. Acta neuropathologica 130, 1-19 (2015).