A5044619237- Circadian rhythm and melatonin
- Cancer Immunotherapy and Biomarkers
- MicroRNA in disease regulation
- Photoreceptor and optogenetics research
- Immunotherapy and Immune Responses
- Genetics, Aging, and Longevity in Model Organisms
- Light effects on plants
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Circular RNAs in diseases
- Plant Molecular Biology Research
- Vasculitis and related conditions
- Sleep and Wakefulness Research
- Hippo pathway signaling and YAP/TAZ
- Extracellular vesicles in disease
- Cellular Mechanics and Interactions
- Ecosystem dynamics and resilience
- Spaceflight effects on biology
- Mineral Processing and Grinding
- Cellular transport and secretion
- Neural dynamics and brain function
- Immune responses and vaccinations
- Gene Regulatory Network Analysis
- Traditional Chinese Medicine Studies
The University of Texas Southwestern Medical Center
2012-2024
Bristol-Myers Squibb (United States)
2023
University of Occupational and Environmental Health Japan
2023
Chinese Academy of Sciences
2008-2021
Crown College
2019
Crown Bioscience (China)
2019
Howard Hughes Medical Institute
2019
Center for Excellence in Molecular Cell Science
2008-2009
Shanghai Institutes for Biological Sciences
2008-2009
The circadian clock in mammals is driven by an autoregulatory transcriptional feedback mechanism that takes approximately 24 hours to complete. A key component of this a heterodimeric activator consisting two basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) domain protein subunits, CLOCK and BMAL1. Here, we report the crystal structure complex containing mouse CLOCK:BMAL1 bHLH-PAS domains at 2.3 Å resolution. reveals unusual asymmetric heterodimer with three each subunits--bHLH, PAS-A,...
Mammalian circadian clocks are driven by a transcription/translation feedback loop composed of positive regulators (CLOCK/BMAL1) and repressors (CRYPTOCHROME 1/2 (CRY1/2) PER1/2). To understand the structural principles regulation, we used evolutionary sequence analysis to identify co-evolving residues within CRY/PHL protein family. Here report identification an ancestral secondary cofactor-binding pocket as interface in repressive CRYs, mediating regulation through direct interaction with...
Cancers are immunologically heterogeneous. A range of immunotherapies target abnormal tumor immunity via different mechanisms actions (MOAs), particularly various tumor-infiltrate leukocytes (TILs). We modeled loss function (LOF) in four common anti-PD-1 antibody-responsive syngeneic tumors, MC38, Hepa1-6, CT-26 and EMT-6, by systematical depleting a series TIL lineages to explore the treatment. CD8+-T-cells, CD4+-T-cells, Treg, NK cells macrophages were individually depleted through either...
Nongenetic cellular heterogeneity is associated with aging and disease. However, the origins of cell-to-cell variability are complex individual contributions different factors to total phenotypic variance still unclear. Here, we took advantage clear circadian oscillations in clonal cell populations investigate underlying mechanisms variability. Using a fully automated tracking analysis pipeline, examined period length thousands single cells hundreds lines found that longer increased...
Programmed cell death protein 1 (PD-1) immune checkpoint blockade therapy has revolutionized cancer treatment. Although PD-1 is effective in a subset of patients with cancer, many fail to respond because either primary or acquired resistance. Thus, next-generation strategies are needed expand the depth and breadth clinical responses. Toward this end, we designed human T phenotypic high-throughput screening strategy identify small molecules distinct complementary mechanisms action blockade....
Adhesion and detachment are coordinated critical steps during cell migration. Conceptually, efficient migration requires both effective stabilization of membrane protrusions at the leading edge via nascent adhesions their successful persistence retraction trailing side disruption focal adhesions. As much smaller in size than adhesions, they expected to exhibit a stronger adhesivity order achieve coordination between front back. Here, we show that Nudel knockdown by interference RNA (RNAi)...
Circadian oscillations are generated via transcriptional-translational negative feedback loops. However, individual cells from fibroblast cell lines have heterogeneous rhythms, oscillating independently and with different period lengths. Here we showed that heterogeneity in circadian is heritable used a multi-omics approach to investigate underlying mechanisms. By examining large-scale phenotype-associated gene expression profiles hundreds of mouse clonal lines, identified validated multiple...
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Li et al., 2015), that described how intended to replicate selected experiments from paper ‘The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44’ (Liu 2011). Here report results. We found microRNA, miR-34a, was expressed at twice level in CD44+ purified xenograft tumors (LAPC4 cells) compared CD44- LAPC4 cells, whereas original study reported underexpressed...
The hypothalamic suprachiasmatic nucleus (SCN) is the central pacemaker for mammalian circadian rhythms. As such, this ensemble of cell-autonomous neuronal oscillators with divergent periods must maintain coordinated oscillations. To investigate ultrastructural features enabling such synchronization, 805 coronal ultrathin sections mouse SCN tissue were imaged electron microscopy and aligned into a volumetric stack, from which selected neurons within core reconstructed in silico. We found...
<h3>Background</h3> Immunoglobulin A associated vasculitis (IgAV), also known as Henoch-Schonlein purpura, is a common systemic vascular inflammatory disease that chiefly manifests skin arthritis, abdominal pain, gastrointestinal bleeding, and kidney involvement [1]. It characterized by immunoglobulin A-dominant immune deposition in small blood vessels, the excessive production of various molecules [2]. Although etiology pathogenesis IgAV are not fully understood, there increasing evidence...
Mammalian circadian rhythms are regulated by a master clock located in the suprachiasmatic nucleus (SCN) of hypothalamus. SCN neurons display self-sustained oscillations that maintained molecular transcriptional-translational feedback loop. Communicative processes between synchronize noisy at single neuron level to generate coherent output tissue selective robustness and plasticity entrain peripheral clocks throughout brain body. The aim this study was digitally reconstruct mouse using...
Abstract Immunological checkpoint inhibitors, i.e., PD1 or PD-L1 antibodies, reverse cancer immunosuppression and promote antitumor immune responses in several types. However, targeting PD-1/PD-L1 axis is only effective ~20% of patients, while some the initial responders also develop resistance to treatment. It critical fully understand which lineages cells play major roles mediating a given tumor microenvironment. While it’s well-known that antibody works through activating cytotoxic T...