A5070423594- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Immune cells in cancer
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Genomics and Chromatin Dynamics
- TGF-β signaling in diseases
- Cancer-related molecular mechanisms research
- Tumors and Oncological Cases
- Retinal Imaging and Analysis
- Ichthyology and Marine Biology
- Glaucoma and retinal disorders
- Pluripotent Stem Cells Research
- Coral and Marine Ecosystems Studies
- Prostate Cancer Treatment and Research
- Identification and Quantification in Food
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Reproductive System and Pregnancy
National Institutes of Health
2008-2025
National Eye Institute
2025
Garvan Institute of Medical Research
2017-2024
The Kinghorn Cancer Centre
2017-2022
St Vincent's Clinic
2018-2022
UNSW Sydney
2018-2022
Christian Health Association of Nigeria
2018
Biodiversity Research Center, Academia Sinica
2013-2015
The tumor immune microenvironment is a main contributor to cancer progression and promising therapeutic target for oncology. However, microenvironments vary profoundly between patients, biomarkers prognosis treatment response lack precision. A comprehensive compendium of cells required pinpoint predictive cellular states their spatial localization. We generated single-cell atlas, jointly analyzing published data sets >500,000 from 217 patients 13 types, providing the basis patient...
There are currently no treatments for geographic atrophy, the advanced form of age-related macular degeneration. Hence, innovative studies needed to model this condition and prevent or delay its progression. Induced pluripotent stem cells generated from patients with atrophy healthy individuals were differentiated retinal pigment epithelium. Integrating transcriptional profiles 127,659 epithelium 43 36 controls genotype data, we identify 445 expression quantitative trait loci in cis that...
The mechanisms by which DNA alleles contribute to disease risk, drug response, and other human phenotypes are highly context-specific, varying across cell types different conditions. Human induced pluripotent stem cells uniquely suited study these context-dependent effects but lines from hundreds or thousands of individuals required. Village cultures, where multiple cultured differentiated in a single dish, provide an elegant solution for scaling experiments the necessary sample sizes...
Background An increasing awareness of the vulnerability sharks to exploitation by shark finning has contributed a growing concern about an unsustainable fishery. Taiwan's fleet 4th largest catch in world, accounting for almost 6% global figures. Revealing diversity consumed Taiwanese is important designing conservation plans. However, fins make up less than 5% total body weight shark, and their bodies are sold as filets market, making it difficult or impossible identify species using...
The latency associated with bone metastasis emergence in castrate-resistant prostate cancer is attributed to dormancy, a state which cells persist prior overt lesion formation. Using single-cell transcriptomics and ex vivo profiling, we have uncovered the critical role of tumor-intrinsic immune signaling retention cell dormancy. We demonstrate that loss type I IFN occurs proliferating bone. This suppresses tumor immunogenicity therapeutic response promotes activation drive progression....
DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, particular cancer-related hypomethylation, affects higher-order levels of architecture is still unclear. Here, using Repli-Seq, single-cell Hi-C, we show that genome-wide methylation loss both concordant precision deregulation 3D organization. Notably, find disruption compartmentalization, striking gains...
High throughput single-cell RNA sequencing (scRNA-Seq) has emerged as a powerful tool for exploring cellular heterogeneity among complex human cancers. scRNA-Seq studies using fresh surgical tissue are logistically difficult, preclude histopathological triage of samples, and limit the ability to perform batch processing. This hindrance can often introduce technical biases when integrating patient datasets increase experimental costs. Although preservation methods have been previously...
Abstract DNA i-motif structures are formed in the nucleus of human cells and believed to provide critical genomic regulation. While existence has been demonstrated by immunofluorescent staining characterisation select model genes, abundance distribution such genome remained unclear. Here we utilize high affinity immunoprecipitation followed sequencing map i-motifs DNA. Validated biolayer interferometry circular dichroism spectroscopy, our approach identified over 650,000 The widely...
To assess the transcriptomic profile of disease-specific cell populations, fibroblasts from patients with primary open-angle glaucoma (POAG) were reprogrammed into induced pluripotent stem cells (iPSCs) before being differentiated retinal organoids and compared those healthy individuals. We performed single-cell RNA sequencing a total 247,520 identified cluster-specific molecular signatures. Comparing gene expression between cases controls, we novel genetic associations for this blinding...
Abstract Patients diagnosed with triple negative breast cancer (TNBC) have an increased risk of rapid metastasis compared to other subtypes. Predicting long-term survival post-chemotherapy in patients TNBC is difficult, yet enhanced infiltration tumor infiltrating lymphocytes (TILs) has been associated therapeutic response and reduced metastatic relapse. Immune biomarkers that predict the immune state a relapse pre- or mid-neoadjuvant chemotherapy are urgently needed allow earlier...
Breast cancers display phenotypic and functional heterogeneity several lines of evidence support the existence cancer stem cells (CSCs) in certain breast cancers, a minor population capable tumor initiation metastatic dissemination. Identifying factors that regulate CSC phenotype is therefore important for developing strategies to treat disease. The Inhibitor Differentiation Protein 1 (Id1) its closely related family member 3 (Id3) (collectively termed Id) are expressed by diversity required...
Abstract Cancers evade the immune system through process of cancer immunoediting. While checkpoint inhibitors are effective for reactivating tumour immunity in some types, many other solid cancers, including breast cancer, remain largely non-responsive. Understanding how non-responsive cancers and whether this occurs at clonal level will improve immunotherapeutic design. Here we use DNA barcoding to track murine mammary cell clones during immunoediting determine transcriptional profiles that...
Abstract The tumor immune microenvironment is a main contributor to cancer progression and promising therapeutic target for oncology. However, microenvironments vary profoundly between patients biomarkers prognosis treatment response lack precision. A comprehensive compendium of cells required pinpoint predictive cellular states their spatial localization. We generated single-cell atlas, jointly analyzing >500,000 from 217 13 types, providing the basis patient stratification based on cell...
Abstract Background Spatial transcriptomic technologies are powerful tools for resolving the spatial heterogeneity of gene expression in tissue samples. However, little evidence exists on relative strengths and weaknesses various available profiling human tumour tissue. In this study, we aimed to provide an objective assessment two common transcriptomics platforms, 10X Genomics’ Visium Nanostring’s GeoMx DSP. Method The abilities DSP platforms profile features were compared using matching...
Inhibitor of differentiation (ID) proteins dimerize with basic HLH (bHLH) transcription factors, repressing lineage-specification genes across diverse cellular lineages. ID4 is a key regulator mammary stem cells; however, the mechanism by which it achieves this unclear. Here, we show that has cell autonomous role in preventing myoepithelial basal cells organoids and vivo. positively regulates proliferative negatively involved function. Mass spectrometry reveals interacts bHLH protein HEB,...
Women with autoimmune and inflammatory aetiologies can exhibit reduced fecundity. TNFAIP3 is a master negative regulator of inflammation, has been linked to many conditions by genome wide associations studies, however its role in fertility remains unknown. Here we show that mice harbouring mild Tnfaip3 reduction-of-function coding variant ( I325N ) reduces the threshold for NF-κB activation, Sub-fertility associated irregular estrous cycling, low numbers ovarian secondary follicles, impaired...
Adrenocortical carcinoma is a rare malignancy with poor prognosis and few treatment options. Molecular characterization of this cancer remains limited. We present case an adrenocortical (ACC) in 37-yr-old female, dual lung metastases identified 1 yr following commencement adjuvant mitotane therapy. As standard therapeutic regimens are often unsuccessful ACC, we undertook comprehensive genomic study into to identify options monitor disease progress. performed targeted whole-genome sequencing...
Searchable abstracts of presentations at key conferences in oncology ISSN 2631-4657 (online)
e24216 Background: Paracrine Hedgehog (Hh) signalling occurs in ~30% of all triple negative breast cancers (TNBCs) and confers worse overall survival. The tumour stroma has been shown to facilitate chemoresistance TNBC. In this study, we investigated the impact inhibiting paracrine Hh sensitise tumours chemotherapy. Methods: For therapeutic studies, NSG mice bearing expressing TNBC (PDX) were randomised treatment with placebo, Smoothened inhibitor (LDE-225), docetaxel, combination LDE-225 +...
Abstract Breast cancer has long been classified into a number of molecular subtypes that predict prognosis and therefore influence clinical treatment decisions. Cellular heterogeneity is also evident in breast cancers plays key role the development, evolution metastatic progression many cancers. How relates to cellular poorly understood, so we approached this question using single cell gene expression analysis well established vitro vivo models disease. To explore first examined panel genes...
Abstract The tumour stroma regulates nearly all stages of carcinogenesis. Stromal heterogeneity in human triple-negative breast cancers (TNBCs) remains poorly understood, limiting the development stromal-targeted therapies. Single cell RNA-sequencing five TNBCs revealed two cancer-associated fibroblast (CAF) and perivascular-like (PVL) subpopulations. CAFs clustered into states, first with features myofibroblasts second characterised by high expression growth factors immunomodulatory...