A5040221728- Cancer Genomics and Diagnostics
- Single-cell and spatial transcriptomics
- Cell Image Analysis Techniques
- Pancreatic and Hepatic Oncology Research
- Lung Cancer Research Studies
- Cancer Cells and Metastasis
- AI in cancer detection
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Radiomics and Machine Learning in Medical Imaging
- Neuroendocrine Tumor Research Advances
- Neuroscience and Neuropharmacology Research
- Cancer, Stress, Anesthesia, and Immune Response
- Tendon Structure and Treatment
- Immune cells in cancer
- Vestibular and auditory disorders
- Peptidase Inhibition and Analysis
- Boron Compounds in Chemistry
- Receptor Mechanisms and Signaling
- Cutaneous lymphoproliferative disorders research
- Cancer Diagnosis and Treatment
- Tribology and Wear Analysis
- Plant nutrient uptake and metabolism
- Plant Molecular Biology Research
- Musculoskeletal synovial abnormalities and treatments
The First Affiliated Hospital, Sun Yat-sen University
2025
Sun Yat-sen University
2025
Memorial Sloan Kettering Cancer Center
2020-2025
Cornell University
2021-2023
Weill Cornell Medicine
2022-2023
Tri-Institutional PhD Program in Chemical Biology
2018-2023
Kettering University
2022-2023
New York Proton Center
2022
Zhejiang University
2016-2019
University of California, Los Angeles
2018
Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes defined by differential expression of ASCL1, NEUROD1, and POU2F3 (SCLC-A, -N, -P, respectively). To define the heterogeneity tumors their associated microenvironments across subtypes, we sequenced 155,098 transcriptomes from 21 human biospecimens, including 54,523 SCLC transcriptomes. We observe greater tumor diversity in than adenocarcinoma, driven canonical, intermediate, admixed subtypes. discover a...
The response to tumor-initiating inflammatory and genetic insults can vary among morphologically indistinguishable cells, suggesting as yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins impact of such plasticity, we performed single-cell analyses on normal, inflamed, premalignant, malignant tissues in autochthonous models pancreatic cancer. We reproducibly identified heterogeneous cell states that are primed diverse, late-emerging...
As cancers progress, they become increasingly aggressive—metastatic tumours are less responsive to first-line therapies than primary tumours, acquire resistance successive and eventually cause death1,2. Mutations largely conserved between metastatic from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression therapy resistance3–5. However, we lack an understanding of cell states mechanisms by which transition. Here, cohort biospecimen...
Abstract Lineage plasticity is a hallmark of cancer progression that impacts therapy outcomes, yet the mechanisms mediating this process remain unclear. Here, we introduce versatile in vivo platform to interrogate neuroendocrine lineage transformation throughout prostate progression. Transplanted mouse organoids with human-relevant driver mutations ( Rb1 − / ; Trp53 cMyc + or Pten ) develop adenocarcinomas, but only those deletion advance aggressive, ASCL1 (NEPC) resistant androgen receptor...
Metastasis is the leading cause of cancer deaths; nonetheless, how tumor cells adapt to vastly different organ contexts largely unknown. To investigate this question, we generated a transcriptomic atlas primary and diverse metastatic samples from patient with pancreatic ductal adenocarcinoma who underwent rapid autopsy. Unsupervised archetype analysis identified both shared site-specific gene programs, including lipid metabolism gastrointestinal programs prevalent in peritoneum stomach wall...
Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape epigenetic modifications. Since 2008, whole-genome bisulfite (WGBS) become gold standard for DNA methylation analysis, and a tremendous amount WGBS data been generated research community. However, systematic comparison profiles to identify regulatory mechanisms yet be fully explored. Here we reprocessed raw over 500 publicly available Arabidopsis libraries from various mutant...
Abstract Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some them become divergent the direction ossification in local pathological microenvironment, thereby representing cellular target for pharmacological approach. We observed that HIF-2alpha (encoded by EPAS1 inclined form) signaling markedly activated within recruited at calcified...
Abstract Defining cellular and subcellular structures in images, referred to as cell segmentation, is an outstanding obstacle scalable single-cell analysis of multiplex imaging data. While advances machine learning-based segmentation have led potentially robust solutions, such algorithms typically rely on large amounts example annotations, known training Datasets consisting annotations which are thoroughly assessed for quality rarely released the public. As a result, there lack widely...
Diffuse-type tenosynovial giant cell tumor (D-TGCT) and localized-type (L-TGCT) share common genomic aberrations histopathological features, but the former has a more aggressive nature higher recurrence rate, leading to worse prognoses for patients. In this study, single-cell RNA sequencing (scRNA-seq) on human D-TGCT L-TGCT lesions is conducted discover transcriptional differences. A unique cluster of cells in identified that regulated differentiation CD34+ fibroblasts into MMP3+ or APOE+...
Abstract Background: Understanding cellular behavior within the context of tumor-immune microenvironment is essential to developing next-generation cancer therapies and advancing precision medicine. The inherent challenges this problem reflect complexity human biology - patient tissue heterogeneity, a multitude interacting signaling pathways, dynamic short- long-range interactions between tumor immune system, intrinsic limitations measurement techniques. Machine Learning foundation models...
ABSTRACT Lineage plasticity is a recognized hallmark of cancer progression that can shape therapy outcomes. The underlying cellular and molecular mechanisms mediating lineage remain poorly understood. Here, we describe versatile in vivo platform to identify interrogate the determinants neuroendocrine transformation at different stages prostate progression. Adenocarcinomas reliably develop following orthotopic transplantation primary mouse organoids acutely engineered with human-relevant...
We report a protocol for obtaining high-quality single-cell transcriptomics data from human lung biospecimens acquired core needle biopsies, fine-needle aspirates, surgical resection, and pleural effusions. The relies upon the brief mechanical enzymatic disruption of tissue, enrichment live cells by fluorescence-activated cell sorting (FACS), droplet-based RNA sequencing (scRNA-seq). also details procedure analyzing scRNA-seq data. For complete on use execution this protocol, please refer to...
ABSTRACT Small cell lung cancer (SCLC) is an aggressive malignancy that includes subtypes defined by differential expression of ASCL1 , NEUROD1 and POU2F3 (SCLC-A, -N, -P, respectively), which are associated with distinct therapeutic vulnerabilities. To define the heterogeneity tumors their microenvironments across subtypes, we sequenced 54,523 cellular transcriptomes from 21 human biospecimens. Our single-cell SCLC atlas reveals tumor diversity exceeding adenocarcinoma, driven canonical,...
Abstract The response to tumor-initiating inflammatory and genetic insults can vary amongst morphologically indistinguishable cells, suggesting yet uncharacterized roles for epigenetic plasticity during early neoplasia. To investigate the origins impact of such plasticity, we perform single-cell analyses on normal, inflamed, pre-malignant malignant tissues in autochthonous models pancreatic cancer. We reproducibly identify heterogeneous cell-states that are primed diverse late-emerging...
A bstract Recent multiplexed protein imaging technologies characterize cells, their spatial organization, and interactions within microenvironments at an unprecedented resolution. Although observational data can reveal associations, it does not allow users to infer salient biological relationships cellular interactions. To address this challenge, we develop a generative model that allows test hypotheses about the effect of cell-cell on expression through in silico perturbation. Our Cell-Cell...
The National Cancer Institute (NCI) supports many research programs and consortia, of which use imaging as a major modality for characterizing cancerous tissue. A trans-consortia Image Analysis Working Group (IAWG) was established in 2019 with mission to disseminate imaging-related work foster collaborations. In 2022, the IAWG held virtual hackathon focused on addressing challenges analyzing high dimensional datasets from fixed tissues. Standard image processing techniques have automated...
<h3>Background</h3> While the field has made significant advances in understanding cancer-immunity cycle and defining patient 'immunotypes', predicting clinical success for a therapeutic given population remains an unsolved problem. Meanwhile, of artificial intelligence (AI) have aided design molecules to drug known targets, but not helped identify novel targets their appropriate populations. Furthermore, recent technological enabled high-resolution, multiplexed spatial profiling cells,...
Abstract Neurons in the medial vestibular nucleus (MVN) display hyperpolarisation-gated synaptic plasticity, where inhibition believed to come from cerebellar cortical Purkinje cells can induce long-term potentiation (LTP) or depression (LTD) of nerve afferent synapses. This phenomenon is thought underlie plasticity vestibulo-ocular reflex (VOR). The molecular and cellular mechanisms involved are largely unknown. Here we present a novel multi-scale computational model, which captures both...
Abstract Lineage plasticity, the ability of cells to transdifferentiate between committed developmental pathways, has been proposed as a source intratumoral heterogeneity and mechanism for tumor adaptation stringent environmental conditions. plasticity is increasingly recognized contributor both drug resistance metastasis, recently highlighted by our team (Quintanal-Villalonga et al., Nat Rev Clin Oncol 2020), thus representing biological phenomenon with high clinical relevance. Leveraging...