A5042723558- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Estrogen and related hormone effects
- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Cancer Research and Treatments
- Single-cell and spatial transcriptomics
- interferon and immune responses
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Cancer Genomics and Diagnostics
- Ferroptosis and cancer prognosis
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Hippo pathway signaling and YAP/TAZ
- RNA Research and Splicing
- Cytokine Signaling Pathways and Interactions
- Epigenetics and DNA Methylation
- Adenosine and Purinergic Signaling
- Colorectal Cancer Treatments and Studies
- Computational Drug Discovery Methods
- Virus-based gene therapy research
- Innovative Microfluidic and Catalytic Techniques Innovation
Stanford University
2023-2025
California Institute for Regenerative Medicine
2023-2025
Palo Alto University
2025
Dana-Farber Cancer Institute
2020-2024
First Affiliated Hospital of Bengbu Medical College
2023-2024
Bengbu Medical College
2023-2024
Tongji University
2018-2024
Tongji Hospital
2023
Harvard University
2021-2022
Manufacturing Advocacy & Growth Network (United States)
2022
Despite growing numbers of immune checkpoint blockade (ICB) trials with available omics data, it remains challenging to evaluate the robustness ICB response and evasion mechanisms comprehensively. To address these challenges, we integrated large-scale data biomarkers on published trials, non-immunotherapy tumor profiles, CRISPR screens a web platform TIDE (http://tide.dfci.harvard.edu). We processed for over 33K samples in 188 cohorts from public databases, 998 tumors 12 clinical studies,...
Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we combined FACS-based genome-wide CRISPR screens a data-mining approach to identify drugs that can upregulate without inducing PD-L1. screening identified TRAF3, suppressor of the NFκB pathway, as negative regulator not The Traf3-knockout gene signature is associated better survival in ICB-naïve and ICB response. We then screened for similar...
Abstract Recent studies have emphasized the importance of single-cell spatial biology, yet available assays for transcriptomics limited gene recovery or low resolution. Here we introduce CytoSPACE, an optimization method mapping individual cells from a RNA sequencing atlas to expression profiles. Across diverse platforms and tissue types, show that CytoSPACE outperforms previous methods with respect noise tolerance accuracy, enabling cartography at
Cancer driver events refer to key genetic aberrations that drive oncogenesis; however, their exact molecular mechanisms remain insufficiently understood. Here, our multi-omics pan-cancer analysis uncovers insights into the impacts of cancer drivers by identifying significant cis-effects and distal trans-effects quantified at RNA, protein, phosphoprotein levels. Salient observations include association point mutations copy-number alterations with rewiring protein interaction networks,...
Single-cell RNA sequencing (scRNA-seq) has transformed our understanding of cell fate in developmental systems. However, identifying the molecular hallmarks potency - capacity a to differentiate into other types remained challenging. Here, we introduce CytoTRACE 2, an interpretable deep learning framework for characterizing and differentiation states on absolute scale from scRNA-seq data. Across 31 human mouse datasets encompassing 28 tissue types, 2 outperformed existing methods recovering...
Abstract Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical strains. They widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional immune system. Large volumes syngeneic expression profiles under different treatments have been generated, although lack systematic collection analysis makes data reuse challenging. We present Tumor Immune MOuse (TISMO), database with an extensive model...
Abstract Drugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell–specific regulators simultaneously modulate tumor immunity and another oncogenic pathway then used it identify 38 candidate immune–metabolic regulators. We show activities of these stratify patients with melanoma by their response anti–PD-1 using machine learning deep neural approaches, which...
Abstract Targeted protein degradation (TPD) has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell’s endogenous machinery. However, susceptibility of for targeting TPD approaches, termed “degradability”, is largely unknown. Here, we developed machine learning model, model-free analysis degradability (MAPD), predict from features intrinsic targets. MAPD shows accurate performance in predicting kinases that are degradable compounds...
Predictive biomarkers of immune checkpoint inhibitor (ICI) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled assessment predictive models by using data two randomized controlled clinical trials (RCTs) ICIs in first-line metastatic NSCLC.
During a successful pregnancy, the maternal immune system plays critical role in maintaining immunotolerance towards semi-allogeneic fetal antigens. Recent studies have indicated that myeloid-derived suppressor cells (MDSCs) are active players establishing fetal-maternal tolerance; however, underlying mechanism remains poorly understood. In this study, we observed significant expansion of monocytic MDSCs (M-MDSCs) peripheral blood pregnant women, which suppressed T cell responses reactive...
Immune checkpoint blockade has shown remarkable efficacy, but in only a minority of patients with cancer, suggesting the need to develop additional treatment strategies. Aberrant glycosylation tumors, resulting from dysregulated expression key enzymes glycan biosynthesis, modulates immune response. However, role biosynthesis antitumor immunity is poorly understood. We aimed study immunomodulatory effects these enzymes.We integrated transcriptional profiles treatment-naïve human tumors and...
Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor following recognition of MHC class I (MHC-I)-bound peptides, but this selection pressure favors outgrowth MHC-I-deficient cells. We performed genome-scale screen discover alternative pathways for cell-mediated killing Autophagy and TNF signaling emerged as top pathways, inactivation Rnf31 (TNF signaling) Atg5 (autophagy) sensitized apoptosis by cell-derived...
Recent advances in single-cell RNA sequencing have shown heterogeneous cell types and gene expression states the non-cancerous cells tumors. The integration of multiple scRNA-seq datasets across tumors can indicate common tumor microenvironment (TME). We develop a data driven framework, MetaTiME, to overcome limitations resolution consistency that result from manual labelling using known markers. Using millions TME single cells, MetaTiME learns meta-components encode independent components...
Abstract Background: Triple-negative breast cancer (TNBC), defined by a lack of hormone receptors and HER2 amplification, is the deadliest subtype cancer. TNBC kills 1 in 3 patients while promising new drugs based on PARP inhibition anti-PD1 immunotherapy can extend survival selected patients, 30-40% relapse or fail therapy. Increasing evidence suggests that tumors harbor stem-like tumorigenic cells with high plasticity, capable replenishing cell populations linked to adverse outcomes....
Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary data suffer from high heterogeneity, low accessibility, lack of controls. In contrast, syngeneic mouse tumor models enable controlled experiments ICB treatments. Using transcriptomic experimental variables >700 ICB-treated/control tumors, we developed a machine learning framework model immunity identify factors influencing response....
Background: Multicellular programs in the tumor microenvironment (TME) drive cancer pathogenesis and response to therapy but remain challenging identify profile clinically. Here, we present Spatial EcoTyper, a multimodal machine learning framework for large-scale profiling of spatially dependent cell states multicellular ecosystems, termed spatial ecotypes (SEs). Methods Findings: By integrating five million single-cell spot-level transcriptomes from 10 diverse human neoplasms, including...
Abstract Background Immune checkpoint blockade (ICB) therapy has improved patient survival in a variety of cancers, but only minority cancer patients respond. Multiple studies have sought to identify general biomarkers ICB response, elucidating the molecular and cellular drivers resistance for individual tumors remains challenging. We determine whether tumor with defined genetic background exhibits stereotypic or heterogeneous response treatment. Results establish unique mouse system that...
We have previously shown that non-cytotoxic concentrations (600-1200 U/ml) of recombinant mouse tumour necrosis factor-alpha (TNF-alpha) can induce differentiation a subclone (JCS) the WEHI-3B myelomonocytic leukaemia cell line into mature cells with characteristics macrophages. In present study, effects interleukin-4 (IL-4), either alone or in combination TNF-alpha, on growth and JCS were examined. IL-4 (20-5000 inhibited dose-dependent manner but did not differentiation. However,...
MHC-II is known to be mainly expressed on the surface of antigen-presenting cells. Evidence suggests also by cancer cells and may associated with better immunotherapy responses. However, role regulation in remain unclear. In this study, we leveraged data mining experimental validation elucidate its modulating response immunotherapy. We collated an extensive collection omics examine cell-intrinsic expression association outcomes. then tested functional relevance using a syngeneic...