A5024413838- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Lung Cancer Treatments and Mutations
- Cancer Immunotherapy and Biomarkers
- Immune cells in cancer
- Colorectal Cancer Treatments and Studies
- Cholangiocarcinoma and Gallbladder Cancer Studies
- RNA modifications and cancer
- Cancer therapeutics and mechanisms
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Pancreatic and Hepatic Oncology Research
- T-cell and B-cell Immunology
- Gut microbiota and health
- Epigenetics and DNA Methylation
- Hepatocellular Carcinoma Treatment and Prognosis
- HER2/EGFR in Cancer Research
- SARS-CoV-2 and COVID-19 Research
- Ubiquitin and proteasome pathways
- COVID-19 Clinical Research Studies
- Diabetes and associated disorders
- Mathematical Biology Tumor Growth
- Biochemical and Molecular Research
National Cancer Institute
2019-2025
Center for Cancer Research
2019-2025
Cancer Institute (WIA)
2024
National Institutes of Health
2022-2023
Guangzhou Medical University
2021-2023
Government of the United States of America
2023
University of Maryland, College Park
2020
The University of Texas Southwestern Medical Center
2019
Nanyang Technological University
2011-2019
City University of Hong Kong
2014-2017
Cellular diversity in tumors is a key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape liver cancer biospecimens from 19 patients. We found varying degrees heterogeneity malignant cells within between diverse landscapes tumor microenvironment (TME). Strikingly, with higher were associated patient's worse overall survival. link hypoxia-dependent vascular endothelial growth expression TME polarization....
Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders; however, its effect on antitumor immunity the liver largely unknown. Here we studied how gut microbiome affects cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma which promote tumor development mice, caused an accumulation of CXCR2+ polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease barrier function mice...
Abstract T-cell exhaustion denotes a hypofunctional state of T lymphocytes commonly found in cancer, but how tumor cells drive remains elusive. Here, we find linked to overall survival 675 hepatocellular carcinoma (HCC) patients with diverse ethnicities and etiologies. Integrative omics analyses uncover oncogenic reprograming HCC methionine recycling elevated 5-methylthioadenosine (MTA) S-adenosylmethionine (SAM) be tightly exhaustion. SAM MTA induce dysfunction vitro. Moreover,...
Abstract Intratumor heterogeneity may result from the evolution of tumor cells and their continuous interactions with microenvironment which collectively drives tumorigenesis. However, an appearance cellular molecular creates a challenge to define features linked malignancy. Here we perform multiregional single-cell RNA sequencing (scRNA-seq) analysis seven liver cancer patients (four hepatocellular carcinoma, HCC three intrahepatic cholangiocarcinoma, iCCA). We identify dynamics malignant...
Therapeutic options for patients with hepatocellular carcinoma (HCC) are limited. Transarterial chemoembolization (TACE) is an interventional procedure used to deliver chemotherapy and embolizing agents directly the tumor of choice intermediate stage HCC. While effective, more than 40% do not respond therapy, highlighting need investigate possible mechanisms resistance. We sought evaluate TACE resistance a potential therapeutic target overcome this resistance.Using prognostic gene signature...
Background and Aims Hepatocellular carcinoma (HCC) is an aggressive malignancy which often associated with a complex tumor microenvironment attributable to etiology‐induced cellular inflammation. γδ T cells are known detect react chronic inflammation, linked cancer development, progression, metastasis. Our recent genomic study revealed increased infiltration of several immune cell types, including cells, in microenvironments Thai HCC subtype good prognosis. Approach Results Here, we...
We conducted a phase II study of the combination pembrolizumab with capecitabine and oxaliplatin (CAPOX) in patients advanced biliary tract carcinoma (BTC) to assess response rate clinical efficacy. Exploratory objectives included correlative studies immune marker expression, tumor evolution, infiltration treatment.
Primary liver cancer is a rising cause of deaths in the US. Although immunotherapy with immune checkpoint inhibitors induces potent response subset patients, rates vary among individuals. Predicting which patients will respond to great interest field. In retrospective arm National Cancer Institute Cancers Liver: Accelerating Research Immunotherapy by Transdisciplinary Network (NCI-CLARITY) study, we use archived formalin-fixed, paraffin-embedded samples profile transcriptome and genomic...
Background and Aims: Hexokinases (HKs), a group of enzymes catalyzing the first step glycolysis, have been shown to play important roles in liver metabolism tumorigenesis. Our recent studies identified HKDC1 as top candidate associated with cancer metastasis. We aimed compare its cell type specificity other HKs upregulated investigate molecular mechanisms underlying involvement Approach Results: found that, compared HK1 HK2, two commonly cancer, was most strongly metastasis potential tumors...
Spatial cellular context is crucial in shaping intratumor heterogeneity. However, understanding how each tumor establishes its unique spatial landscape and what factors drive the for fitness remains significantly challenging. Here, we analyzed over 2 million cells from 50 biospecimens using single-cell imaging RNA sequencing. We developed a deep learning-based strategy to spatially map cell states architecture surrounding them, which referred as Dynamics Network (SDN). found that different...
Stochastic optimization of computationally expensive problems is a relatively new field research in evolutionary computation (EC). At present, few EC works have been published to handle plagued with constraints that are compute. This paper presents surrogate-assisted memetic co-evolutionary framework tackle both facets practical problems, i.e. the having objectives and constraints. In contrast existing works, cooperative mechanism adopted as backbone improve efficiency techniques. The idea...
Metastatic non-small-cell lung cancer (NSCLC) with activating EGFR mutations responds very well to first and second generation tyrosine-kinase inhibitors (TKI) including gefitinib, erlotinib afatinib. Unfortunately, drug resistance will eventually develop about half of the cases are secondary emergence acquired T790M somatic mutation. In this work, we prospectively recruited 68 patients metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI or without...
Epidermal growth factor receptor (EGFR) mutation-induced drug resistance has caused great difficulties in the treatment of non-small-cell lung cancer (NSCLC). However, structural information is available for just a few EGFR mutants. In this study, we created an Mutant Structural Database (freely at http://bcc.ee.cityu.edu.hk/data/EGFR.html ), including 3D mutant structures and their corresponding binding free energies with two commonly used inhibitors (gefitinib erlotinib).We collected 942...
EGFR mutation-induced drug resistance has become a major threat to the treatment of non-small-cell lung carcinoma. Essentially, mechanism involves modifications intracellular signaling pathways. In our work, we separately investigated and ErbB-3 heterodimerization, regarded as origin On one hand, combined molecular interaction in heterodimerization with that between tyrosine kinase its inhibitor. For 168 clinical subjects, characterized their corresponding mutations using interactions, three...
Background and Aims: The fitness viability of a tumor ecosystem are influenced by the spatial organization its cells. We aimed to study structure, architecture, cell-cell dynamics heterogeneous liver cancer microenvironment using spatially resolved multiplexed imaging. Approach Results: performed co-detection indexing immunofluorescence imaging on 68 HCC biopsies from Thai patients [(Thailand Initiative in Genomics Expression Research for Liver Cancer (TIGER-LC)] as discovery cohort, then...
Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC iCCA remains underexplored. Here, we present genome-wide profiling regulatory elements 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing. Single-cell open profiles reflect the compositional diversity cancer,...
The study of the tumor microbiome has been garnering increased attention. We developed a computational pipeline (CSI-Microbes) for identifying microbial reads from single-cell RNA sequencing (scRNA-seq) data and analyzing differential abundance taxa. Using series controlled experiments analyses, we performed first systematic evaluation efficacy recovering unique molecular identifiers by multiple scRNA-seq technologies, which identified newer 10x chemistries (3' v3 5') as best suited...