A5070861002- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Ferroptosis and cancer prognosis
- Thyroid Cancer Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Multiple Myeloma Research and Treatments
- Bioinformatics and Genomic Networks
- Cancer Cells and Metastasis
- Lung Cancer Treatments and Mutations
- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- PARP inhibition in cancer therapy
- Wheat and Barley Genetics and Pathology
- Endometrial and Cervical Cancer Treatments
- Molecular Biology Techniques and Applications
- Cancer Immunotherapy and Biomarkers
- Prostate Cancer Treatment and Research
- Genetic Mapping and Diversity in Plants and Animals
- Epigenetics and DNA Methylation
- Ovarian cancer diagnosis and treatment
- Plant Molecular Biology Research
China National Rice Research Institute
2024
China Agricultural University
2024
The University of Texas MD Anderson Cancer Center
2020-2023
The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated (DTC); however, the complex intra-tumor transformation process is poorly understood. We investigated an model by dissecting both cell lineage and fate transitions using single transcriptomes genetic alteration data patients with different subtypes of cancer. resulting spectrum ATC included stress-responsive DTC cells, inflammatory cells (iATCs), mitotic-defective extended all way to mesenchymal...
Abstract Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response antiangiogenic therapy leading emergence of adaptive resistance. By using both RNA-aptamer monoclonal antibody CD5L, we are able abate pro-angiogenic effects overexpression vitro vivo settings. In addition,...
Abstract High-throughput methods for single cell copy number sequencing have enabled the profiling of thousands cells in parallel, yet there remains a significant bottleneck data analysis. Here we present CopyKit, comprehensive set computational pre-processing and analysis to resolve clonal substructure reconstruct genetic lineages tumors. We performed DNA 2977 from multiple spatial regions two liver metastasis 7365 three primary tumors with matched metastatic tissues. In metastases, CopyKit...
Panicle architecture is an agronomic determinant of crop yield and a target for cereal improvement. To investigate its molecular mechanisms in rice, we performed map-based cloning characterization OPEN PANICLE 1 (OP1), gain-of-function allele LIGULELESS (LG1), controlling the spread-panicle phenotype. This results from 48-bp deletion LG1 upstream region promotes pulvinus development at base primary branch. Increased OP1 expression altered panicle phenotype pC1 chimeric transgenic plants...
Abstract Advances in single cell copy number sequencing technologies have enabled the generation of data on hundreds to thousands cells parallel. Despite rapid development these technologies, there is a significant bottleneck for analysis resulting large-scale datasets. Here we present CopyKit, comprehensive and user-friendly toolkit data. CopyKit provides suite tools pre-processing, QC, inference, subclone clustering delineate clonal diversity tumors. We performed 2977 from two breast tumor...
Abstract Triple-negative breast cancer (TNBC) is an aggressive subtype of that lacks the expression estrogen receptor (ER), progesterone (PR) and HER2 therefore have limited hormonal treatment options. Neoadjuvant chemotherapy (NAC) backbone for TNBC, about 50% patients respond well leading to pathological complete response (pCR). However, remaining develop resistance NAC progress metastatic disease poor survival in 1-2 years after initial treatment. Previous studies performed bulk RNA...
Abstract Ductal carcinoma in situ (DCIS) is a common precursor of invasive breast cancer (IBC), yet the genomic progression to recurrent disease remains poorly understood. A main contributor this gap knowledge arises from technical challenges with profiling formalin-fixed paraffin-embedded (FFPE) materials. To address challenge, we developed Arc-well, first high-throughput method that can perform single cell DNA sequencing thousands cells FFPE materials and frozen tissues. Using profiled...
Abstract Background: Despite advances in cancer diagnosis and therapy, high-grade serous ovarian (HGSC) is often diagnosed when spread to multiple intraperitoneal areas; it prone metastasize adipose-rich tissues such as the omentum. To gain a deeper understanding of molecular determinants HGSC milieu, we carried out single-cell analysis primary metastatic tumors HGSC. Thus, our aim identify mechanisms that lead immunosuppressive Methods: Fresh surgical samples from 19 patients were collected...
Abstract The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated (DTC), however the complex intra-tumor transformation process is poorly understood. We investigated an model by dissecting both cell lineage and fate transitions using single transcriptomes genetic alterations data of patients with different subtypes cancer. resulting started stress-responsive DTC cells to inflammatory ATC cells, mitotic defective extended all way mesenchymal cells. In...
Abstract Ductal-carcinoma-in-situ (DCIS) is the most common early-stage breast cancer and a non-obligate precursor to invasive cancer. However our understanding of spatial microenvironment reprogramming cell types in DCIS remains limited. To address this question, we developed Spatial Nucleus Barcoding (SNuBar) method that utilizes single oligonucleotide adaptor preserve information followed by performing nucleus RNA sequencing. We validated accuracy scalability SNuBar lines applied...
Abstract Single cell DNA sequencing (scDNA-seq) methods are powerful tools for profiling mutations in cancer cells, however most genomic regions characterized single cells non-informative. To overcome this issue, we developed a Multi-Patient-Targeted (MPT) scDNA-seq method. MPT involves first performing bulk exome across cohort of patients to identify somatic mutations, which then pooled together develop custom targeted panel high-throughput using microfluidics platform. We applied profile...
Abstract Chemoradiation (CRT) is widely used to treat locally advanced non-small cell lung cancer (NSCLC) patients, but only around 30% of patients achieve pathological complete response. Here, we utilized an in vitro high-content clonogenic survival screening method identify CRT sensitizers from the NCI Cancer Therapy Evaluation Program (CTEP) portfolio. Talazoparib (PARPi) was identified among top candidates show potent sensitization effects both KRAS mutant and TP53 NCSLC lines. We...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal tumor-type with very few effective treatment strategies. Attempts to improve outcomes using immune checkpoint blockade therapy have also failed, likely because the overall Tcell infiltration in this low. Despite this, presence of CD3+CD8+ tumor-infiltrating lymphocytes (TIL) PDAC associated improved survival outcomes, suggesting that other immune-based strategies could be more successful. Here, we examine ex vivo expansion...
Abstract Single cell RNA sequencing (scRNA-seq) methods can profile the transcriptomes of single cells but cannot preserve spatial information. Conversely, transcriptomics (ST) assays regions in tissue sections do not have genomic resolution. To address this issue, computational approaches (e.g., cell2location, RCTD) been designed to deconvolute ST spots into proportions different types. However, deconvolution method has following limitations, 1) it only infer type each spot and reach higher...
Abstract Prostate cancer is the most commonly diagnosed among men and a major cause of cancer-related deaths in modern world. Metastatic castration-resistant prostate (mCRPC) lethal form has complex heterogeneous genomic patterns. Despite recent development life-prolonging therapies, mCRPC remains incurable since patients develop resistance over time. A better understanding evolution to therapy urgently needed. logistical challenge that collecting serial tissue biopsies from metastatic sites...
Abstract Ductal carcinoma in situ (DCIS) is early-stage non-malignant breast cancer that tumor cells are confined to the lumens of ducts. Over 50,000 DCIS patients diagnosed each year United States, however, less than half will develop into invasive (IBC), suggesting a risk overtreatment for some patients. A comprehensive investigation molecular mechanisms initiation and progression urgently needed can facilitate us stratifying invasion design better intervention approaches. In this study,...