A5004157906- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Neurogenetic and Muscular Disorders Research
- Lysosomal Storage Disorders Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Axon Guidance and Neuronal Signaling
- Nerve injury and regeneration
- Mass Spectrometry Techniques and Applications
- Microtubule and mitosis dynamics
- RNA regulation and disease
- DNA Repair Mechanisms
- Cellular transport and secretion
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Autophagy in Disease and Therapy
- Fungal and yeast genetics research
- Pancreatic function and diabetes
- Isotope Analysis in Ecology
- Neurogenesis and neuroplasticity mechanisms
- Angiogenesis and VEGF in Cancer
- interferon and immune responses
Cornell University
2016-2025
Nanjing Drum Tower Hospital
2022-2023
Jiangsu University
2023
Intel (United Kingdom)
2023
Nanjing Medical University
2022
National University of Defense Technology
2014
Peking Union Medical College Hospital
2013
Academy of Medical Sciences
2013
Chinese Academy of Medical Sciences & Peking Union Medical College
2013
Yale University
2004-2010
In response to DNA damage, cells activate checkpoint pathways that prevent cell cycle progression. fission yeast and mammals, mitotic arrest in damage requires inhibitory Cdk phosphorylation regulated by Chk1. This study indicates Chk1 is required for function of the Saccharomyces cerevisiae but acts through a distinct mechanism maintaining abundance Pds1, an anaphase inhibitor. Unlike other mutants, chk1 mutants were only mildly sensitive indicating functions besides influence sensitivity....
Hexanucleotide repeat expansion in the C9orf72 gene is a leading cause of frontotemporal lobar degeneration (FTLD) with amyotrophic lateral sclerosis (ALS). Reduced expression has been proposed as possible disease mechanism. However, cellular function remains to be characterized. Here we report identification two binding partners C9orf72: SMCR8 and WDR41. We show that WDR41 interacts C9orf72/SMCR8 heterodimer tightly associated Golgi complex. further demonstrate C9orf72/SMCR8/WDR41...
TAR DNA-binding protein-43 (TDP-43) proteinopathy has been linked to several neurodegenerative diseases, such as frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Phosphorylated ubiquitinated TDP-43 C-terminal fragments have found in cytoplasmic sclerosis patients. However, the factors pathways that regulate aggregation are still not clear. We 15 kDa fragment of is sufficient induce but phenotype modified by additional sequences....
Haploinsufficiency of Progranulin (PGRN), a gene encoding secreted glycoprotein, is major cause frontotemporal lobar degeneration with ubiquitin (FTLD-U) positive inclusions. Single nucleotide polymorphisms in the TMEM106B were recently discovered as risk factor for FTLD-U, especially patients PGRN mutations. also associated cognitive impairment amyotrophic lateral sclerosis patients. Despite these studies, little known about at molecular and cellular levels how contributes to FTLD. Here, we...
Mutations in the progranulin (PGRN) gene have been linked to two distinct neurodegenerative diseases, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests a critical role of PGRN lysosomes. However, how is trafficked lysosomes still not clear. Here we report novel pathway for lysosomal delivery PGRN. We found that prosaposin (PSAP) interacts with facilitates its targeting both biosynthetic endocytic pathways via cation-independent...
Abstract Haploinsufficiency of progranulin (PGRN) due to mutations in the granulin ( GRN ) gene causes frontotemporal lobar degeneration (FTLD), and complete loss PGRN leads a lysosomal storage disorder, neuronal ceroid lipofuscinosis (NCL). Accumulating evidence suggests that is essential for proper function, but precise mechanisms involved are not known. Here, we show facilitates uptake delivery prosaposin (PSAP), precursor saposin peptides glycosphingolipid degradation. We found reduced...
Haploinsufficiency of progranulin (PGRN) is a leading cause frontotemporal lobar degeneration (FTLD). Loss PGRN leads to lysosome dysfunction during aging. TMEM106B, gene encoding lysosomal membrane protein, the main risk factor for FTLD with haploinsufficiency. But how TMEM106B affects disease progression remains be determined. Here, we report that deficiency in mice accumulation vacuoles at distal end axon initial segment motor neurons and development FTLD-related pathology Ablation both...
The TMEM106B gene, encoding a lysosomal membrane protein, is closely linked with brain aging and neurodegeneration. has been identified as risk factor for several neurodegenerative diseases characterized by aggregation of the RNA-binding protein TDP-43, including frontotemporal lobar degeneration (FTLD) limbic-predominant age-related TDP-43 encephalopathy (LATE). To investigate role in proteinopathy, we ablated TDP-43Q331K knock-in mouse line, which expresses an ALS-linked mutation at...
Yeast defective in the checkpoint kinase Rad53 fail to recover from transient DNA replication blocks and synthesize intact chromosomes. The effectors of relevant this recovery process are unknown. Here we report that overproduction chromatin assembly factor Asf1 can suppress Ts phenotype mrc1rad53 double mutants HU sensitivity rad53 mutants. Eliminating silencing also suppresses lethality, further implicating structure function. We find exist a dynamic complex dissociates response damage....
Nogo isoforms (Nogo-A and -B) have been implicated in regulating neural cardiovascular functions, such as cell spreading chemotaxis. Unlike the loop domain (Nogo-66) found all that can interact with a neural-specific Nogo-66 receptor, receptor for amino terminus of Nogo-B mediates vascular function is unknown. Here, we identify previously uncharacterized specific show localizes ligand during VEGF wound healing angiogenesis vivo, chemotaxis heterologous expression system chemotaxis, 3D tube...
Myelin-derived Nogo-A protein limits axonal growth after CNS injury. One domain binds to the Nogo-66 receptor inhibit outgrowth, whereas a second domain, Amino-Nogo, inhibits outgrowth and cell adhesion through unknown mechanisms. Here, we show that Amino-Nogo inhibition depends strictly on composition of extracellular matrix, suggesting function certain integrins. can be partially overcome by antibodies activate integrin β1 or addition Mn 2+ , an activator. Furthermore, reduces focal kinase...
In schizophrenia, genetic predisposition has been linked to chromosome 22q11 and myelin-specific genes are misexpressed in schizophrenia. Nogo-66 receptor 1 ( NGR or RTN4R ) considered be a candidate gene for schizophrenia susceptibility because it encodes an axonal protein that mediates myelin inhibition of sprouting. Confirming previous studies, we found variation at the locus is associated with Caucasian case-control analysis, this association not attributed population stratification....
Progranulin haplo-insufficiency is a main cause of frontotemporal lobar degeneration (FTLD) with TDP-43 aggregates. Previous studies have shown that sortilin regulates progranulin trafficking and determinant level in the brain. In this study, we mapped binding site between sortilin. binds to beta-propeller region through its C-terminal tail. The fragment fully sufficient for peptide displaces Deletion last 3 residues (QLL) abolishes also dependent regulation trafficking. Since results FTLD,...
Mutations resulting in progranulin (PGRN) haploinsufficiency cause frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), a devastating neurodegenerative disease. PGRN is localized to the lysosome and important for proper function. However, metabolism of still unclear.Here, we report that processed into ~10 kDa peptides intracellularly multiple cell types tissues this processing dependent on lysosomal activities. endocytosed from extracellular space also similar...
Mutation in the GRN gene, encoding progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results frontotemporal lobar degeneration (FTLD) and complete loss neuronal ceroid lipofuscinosis (NCL). Although exact function of PGRN is unknown, it has been increasingly implicated lysosomal physiology. Here we report that interacts with enzyme, glucocerebrosidase (GCase), essential for proper GCase activity. activity significantly reduced tissue lysates...