- Glioma Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Meningioma and schwannoma management
- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- Neuroblastoma Research and Treatments
- Neurofibromatosis and Schwannoma Cases
- Epigenetics and DNA Methylation
- Chronic Disease Management Strategies
- Brain Metastases and Treatment
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Health disparities and outcomes
- Intraocular Surgery and Lenses
- Health Systems, Economic Evaluations, Quality of Life
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- Neurogenesis and neuroplasticity mechanisms
- Peptidase Inhibition and Analysis
University of California, San Francisco
2016-2025
Neurological Surgery
2016-2025
Sun Yat-sen University
2023-2025
Southern Medical University
2021-2025
World Health Organization
2025
Northeast Forestry University
2025
Heilongjiang Academy of Sciences
2025
Xi'an Shiyou University
2025
University of Göttingen
2024
Chinese PLA General Hospital
2022-2024
Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages maturation and differentiation coexist in the emerging tissues. We identified discrete as well temporally spatially restricted radial glia neurogenesis developing human telencephalon. These lineage-specific reveal neurogenic transcription factors early enriched activation mammalian target rapamycin signaling outer glia. Across cortical...
A very focused function for lncRNAs The human genome generates many thousands of long noncoding RNAs (lncRNAs). small number have been shown to be functional. Liu et al. carried out a large-scale CRISPR-based screen assess the ∼17,000 in seven different cell lines. considerable (∼500) tested influenced growth, suggesting biological function. In almost all cases, though, was highly type—specific, often limited just one type. Science , this issue p. 10.1126/science.aah7111
Tumor-associated macrophages (TAMs) are abundant in gliomas and immunosuppressive TAMs a barrier to emerging immunotherapies. It is unknown what extent derived from peripheral blood adopt the phenotype of brain-resident microglia pre-treatment gliomas. The relative proportions blood-derived have been poorly quantified clinical samples due paucity markers that distinguish these cell types malignant tissue. We perform single-cell RNA-sequencing human identify phenotypic differences distinct...
Cell fate decisions are fundamental for development, but we do not know how transcriptional networks reorganize during the transition from a pluripotent to differentiated cell state. Here, asked mouse embryonic stem cells (ESCs) leave state and choose between germ layer fates. By analyzing dynamics of circuit that maintains pluripotency, found Oct4 Sox2, proteins maintain ESC identity, also orchestrate selection. suppresses neural ectodermal differentiation promotes mesendodermal...
Long non-coding RNAs (lncRNAs) comprise a diverse class of transcripts that can regulate molecular and cellular processes in brain development disease. LncRNAs exhibit cell type- tissue-specific expression, but little is known about the expression function lncRNAs developing human brain. Furthermore, it has been unclear whether are highly expressed subsets cells within tissues, despite appearing lowly bulk populations. We use strand-specific RNA-seq to deeply profile from polyadenylated...
Acute myocardial infarction (MI) involves necrotic and apoptotic loss of cardiomyocytes. One strategy to salvage ischemic cardiomyocytes is modulate gene expression promote cell survival without disturbing normal cardiac function. MicroRNAs (miRNAs) have emerged as powerful regulators multiple cellular processes, including apoptosis, suggesting that regulation miRNA function could serve a cardioprotective In this study, we report miR-24 (miRNA-24) down-regulated in the border zone murine...
Glioblastoma is a devastating form of brain cancer. To identify aspects tumor heterogeneity that may illuminate drivers invasion, we created glioblastoma cell atlas with single-cell transcriptomics cancer cells mapped onto reference framework the developing and adult human brain. We find multiple GSC subtypes exist within single tumor. Within these GSCs, an invasive population similar to outer radial glia (oRG), fetal type expands stem niche in normal cortex. Using live time-lapse imaging...
Small-cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with a high relapse rate, limited therapeutic options, and poor prognosis. We investigated the antitumor activity of AMG 757, half-life extended bispecific T-cell engager molecule targeting delta-like ligand 3 (DLL3)-a target that selectively expressed in SCLC tumors, but minimal normal tissue expression.
Autoreactive CD4 T cells that differentiate into pathogenic Th17 can trigger autoimmune diseases. Therefore, investigating the regulatory network modulates differentiation may yield important therapeutic insights. miR-146a has emerged as a critical modulator of immune reactions, but its role in regulating autoreactive and organ-specific autoimmunity remains largely unknown. Here, we have reported miR-146a-deficient mice developed more severe experimental encephalomyelitis (EAE), an animal...
The epigenetic mechanisms that enable lifelong neurogenesis from neural stem cells (NSCs) in the adult mammalian brain are poorly understood. Here, we show JMJD3, a histone H3 lysine 27 (H3K27) demethylase, acts as critical activator of subventricular zone (SVZ) NSCs. JMJD3 is upregulated neuroblasts, and Jmjd3 deletion targeted to SVZ NSCs both developing mice impairs neuronal differentiation. regulates neurogenic gene expression via interaction at not only promoter regions but also...
Article25 November 2016Open Access Transparent process Single-cell sequencing maps gene expression to mutational phylogenies in PDGF- and EGF-driven gliomas Sören Müller Department of Neurological Surgery, University California San Francisco, CA, USA Eli Edythe Broad Center Regeneration Medicine Stem Cell Research, Search for more papers by this author Siyuan John Liu Elizabeth Di Lullo Neurology, Martina Malatesta Alex A Pollen Tomasz J Nowakowski Gary Kohanbash Manish Aghi Arnold R...
Abstract Background Long non-coding RNAs (lncRNAs) exhibit highly cell type-specific expression and function, making this class of transcript attractive for targeted cancer therapy. However, the vast majority lncRNAs have not been tested as potential therapeutic targets, particularly in context currently used treatments. Malignant glioma is rapidly fatal, ionizing radiation part current standard-of-care to slow tumor growth both adult pediatric patients. Results We use CRISPR interference...
Since the outbreak of COVID-19, a variety vaccine platforms have been developed. Amongst these, inactivated vaccines authorized for emergency use or conditional marketing in many countries. To further enhance protective immune responses populations that completed vaccination regimen, we investigated immunogenic characteristics different and tried homologous heterologous boost strategy post two doses mouse model. Our results showed humoral cellular induced by when administered individually...
Abstract Meningiomas are the most common primary intracranial tumors, but molecular drivers of meningioma tumorigenesis poorly understood. We hypothesized that investigating intratumor heterogeneity in meningiomas would elucidate biologic and reveal new targets for therapy. To test this hypothesis, here we perform multiplatform profiling 86 spatially-distinct samples from 13 human meningiomas. Our data regional alterations chromosome structure underlie clonal transcriptomic, epigenomic,...
Abstract Migrasomes are organelles that generated by migrating cells. Here we report the key role of neutrophil-derived migrasomes in haemostasis. We found a large number exist blood mice and humans. Compared with neutrophil cell bodies platelets, these adsorb enrich coagulation factors on surface. Moreover, they highly enriched adhesion molecules, which enable them to preferentially accumulate at sites injury, where trigger platelet activation clot formation. Depletion neutrophils, or...
Abstract Mechanisms specifying cancer cell states and response to therapy are incompletely understood. Here we show epigenetic reprogramming shapes the cellular landscape of schwannomas, most common tumors peripheral nervous system. We find schwannomas comprised 2 molecular groups that distinguished by activation neural crest or nerve injury pathways specify tumor architecture immune microenvironment. Moreover, radiotherapy is sufficient for interconversion immune-enriched through metabolic...
Long noncoding RNAs (lncRNAs) account for the largest portion of RNA from transcriptome, yet most their functions remain unknown. Here, we performed two independent high-throughput CRISPRi screens to understand role lncRNAs in monocyte function and differentiation. The first was a reporter-based screen identify that regulate TLR4-NFkB signaling human monocytes second identified involved macrophage We successfully numerous protein-coding genes can positively or negatively inflammation To...
Abstract Background Glioblastoma (GBM) carries a poor prognosis, and new therapeutic strategies are necessary to improve outcomes for patients with this disease. Alkylating chemotherapies including temozolomide (TMZ) lomustine (CCNU) critical treating GBM, but resistance mechanisms, hypomethylation of O6-methylguanine-DNA methyltransferase (MGMT) promoter, undermine treatment. CRISPRoff is programmable epigenetic memory editor that can induce stable heritable gene silencing after transient...
Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate family, plays role glycolytic enzyme in glucose metabolism. It also functions protein cell proliferation, signaling, immunity, and gene transcription. In this study, the PKM2 neuropathic pain induced by chronic constriction injury (CCI) was investigated.Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated kinases (EKR), p-ERK, signal transducers activators transcription (STAT3), p-STAT3, phosphoinositide...