A5035887405- T-cell and B-cell Immunology
- Neuroscience and Neuropharmacology Research
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- DNA Repair Mechanisms
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Immune Cell Function and Interaction
- Cellular transport and secretion
- Neuroinflammation and Neurodegeneration Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Ion channel regulation and function
- High voltage insulation and dielectric phenomena
- Tryptophan and brain disorders
- Alzheimer's disease research and treatments
- Force Microscopy Techniques and Applications
- Cell death mechanisms and regulation
- PI3K/AKT/mTOR signaling in cancer
- Geotechnical Engineering and Underground Structures
- Endoplasmic Reticulum Stress and Disease
- Nerve injury and regeneration
- Axon Guidance and Neuronal Signaling
- PARP inhibition in cancer therapy
South China University of Technology
2023-2025
Hong Kong University of Science and Technology
2012-2024
University of Hong Kong
2012-2024
Harvard University
2018-2023
Boston Children's Hospital
2018-2023
Boston Children's Museum
2021-2023
Howard Hughes Medical Institute
2018-2021
Life University
2015
Abnormal deposition of brain amyloid is a major hallmark Alzheimer's disease (AD). The toxic extracellular plaques originating from the aberrant aggregation beta-amyloid (Aβ) protein are considered to be cause clinical deficits such as memory loss and cognitive impairment. Two-photon excited fluorescence (TPEF) microscopy provides high spatial resolution, minimal invasiveness, long-term monitoring capability. TPEF imaging in AD transgenic mice models has greatly facilitated studies...
Abstract Dendritic spine stabilization depends on afferent synaptic input and requires changes in actin cytoskeleton dynamics protein synthesis. However, the underlying molecular mechanism remains unclear. Here we report identification of ‘calmodulin kinase-like vesicle-associated’ (CaMKv), a pseudokinase CaMK family with unknown function, as crucial for dendritic maintenance. CaMKv mRNA localizes at dendrites, its synthesis is regulated by neuronal activity. function inhibited upon...
Immunoglobulin heavy chain variable region exons are assembled in progenitor-B cells, from V
The proper growth and arborization of dendrites in response to sensory experience are essential for neural connectivity information processing the brain. Although neuronal activity is important sculpting dendrite morphology, underlying molecular mechanisms not well understood. Here, we report that cyclin-dependent kinase 5 (Cdk5)-mediated transcriptional regulation a key mechanism controls activity-dependent development cultured rat neurons. During membrane depolarization, Cdk5 accumulates...
Significance Alternative end joining (A-EJ) is implicated in oncogenic translocations and mediating DNA double-strand-break (DSB) repair cycling cells when classical nonhomologous end-joining (C-NHEJ) factors of the C-NHEJ ligase complex are absent. However, V(D)J recombination-associated DSBs that occur G1 cell cycle-phase progenitor lymphocytes joined exclusively by pathway. Until now, however, overall mechanisms join general G1-phase B had not been fully elucidated. Here, we report Ku, a...
The maturation and maintenance of dendritic spines depends on neuronal activity protein synthesis. One potential mechanism involves mammalian target rapamycin, which promotes synthesis through phosphorylation eIF4E-binding p70 ribosomal S6 kinase 1 (S6K). Upon extracellular stimulation, rapamycin phosphorylates S6K at Thr-389. also undergoes other sites, including four serine residues in the autoinhibitory domain. Despite extensive biochemical studies, importance domain function remains...
During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin ("axis inhibitor") is a key protein in canonical Wnt interacts with specific synaptic proteins. However, the cellular functions of these protein–protein interactions regulation are unclear. Here, we report enriched fractions, colocalizes postsynaptic marker PSD-95...
The experience-dependent modulation of brain circuitry depends on dynamic changes in synaptic connections that are guided by neuronal activity. In particular, postsynaptic maturation requires dendritic spine morphology, the targeting proteins, and insertion neurotransmitter receptors. Thus, it is critical to understand how activity controls maturation. Here we report scaffold protein liprinα1 its phosphorylation cyclin-dependent kinase 5 (Cdk5) for excitatory synapses through regulation...
The B-cell antigen receptor (BCR) is composed of a membrane-bound immunoglobulin (mIg) class M, D, G, A or E for recognition and disulfide-linked heterodimer between Igα Igβ (Igα/β, also known as CD79A CD79B) that functions the signalling entity. organizing principle BCR assembly remains elusive. Here we report cryo-electron microscopy structures intact IgM at 8.2 Å resolution its Fab-deleted form (IgM BCRΔFab) 3.6 resolution. At ectodomain (ECD), position their respective Ig folds roughly...
Amyloid depositions in the brain represent characteristic hallmarks of Alzheimer's disease (AD) pathology. The abnormal accumulation extracellular amyloid-beta (Aβ) and resulting toxic amyloid plaques are considered to be responsible for clinical deficits including cognitive decline memory loss. In vivo two-photon fluorescence imaging live AD mouse model through a chronic window (thinned skull or craniotomy) provides mean greatly facilitate study pathological mechanism owing its high spatial...
We provide a protocol for neural blastocyst complementation \(NBC), method we have developed studying development and function of speci c forebrain regions.We describe all experimental steps from genetically modifying locus interest, via CRISPR/Cas9 editing in mouse embryonic stem cells \ (ESCs), to generating chimeric mice with ESC-reconstituted regions that can be directly analyzed.Our _in vivo_ brain organogenesis approach is e cient, allowing functional systematic analysis genes \(or...
Abstract Classical nonhomologous end-joining (C-NHEJ) repairs DNA double-stranded breaks (DSBs) throughout interphase but predominates in G1-phase when homologous recombination is unavailable. Complexes containing the Ku70/80 (“Ku”) and XRCC4/Ligase IV (Lig4) core C-NHEJ factors are required, respectively, for sensing joining DSBs. While absolutely required RAG1/2-endonucease (“RAG”)-initiated DSBs during V(D)J progenitor lymphocytes, cycling cells deficient also can join chromosomal by...