Joanna N. Skhinas
A5003062884- Cancer Cells and Metastasis
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Microbial metabolism and enzyme function
- Bone Tissue Engineering Materials
- Wnt/β-catenin signaling in development and cancer
- Acute Myeloid Leukemia Research
- Cancer Research and Treatments
- Glioma Diagnosis and Treatment
- Cancer-related gene regulation
- Estrogen and related hormone effects
- Erythrocyte Function and Pathophysiology
- Developmental Biology and Gene Regulation
- Inflammatory mediators and NSAID effects
- Pancreatic and Hepatic Oncology Research
- Renal cell carcinoma treatment
- Zebrafish Biomedical Research Applications
- Hippo pathway signaling and YAP/TAZ
- Caveolin-1 and cellular processes
- Angiogenesis and VEGF in Cancer
- Redox biology and oxidative stress
- Protease and Inhibitor Mechanisms
- Epigenetics and DNA Methylation
Garvan Institute of Medical Research
2017-2024
The Kinghorn Cancer Centre
2017-2024
Children's Cancer Institute Australia
2024
Cancer Institute (WIA)
2024
UNSW Sydney
2017-2023
Cancer Institute of New South Wales
2022-2023
Pancreatic Cancer Action Network
2021
St Vincent's Clinic
2017
Abstract The cellular and molecular basis of stromal cell recruitment, activation crosstalk in carcinomas is poorly understood, limiting the development targeted anti-stromal therapies. In mouse models triple negative breast cancer (TNBC), Hedgehog ligand produced by neoplastic cells reprograms cancer-associated fibroblasts (CAFs) to provide a supportive niche for acquisition chemo-resistant, stem (CSC) phenotype via FGF5 expression production fibrillar collagen. Stromal treatment...
The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays crucial role shaping their progression. Many desmoplastic including breast cancer involve significant accumulation type I collagen. However, recently it has become clear precise distribution organisation molecules such as collagen equally important abundance. Cancer-associated fibroblasts (CAFs) coexist within tissues play both pro- anti-tumourigenic roles through remodelling...
Abstract The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance this crosslinking and stabilizing fibrillar collagens its known role tumor desmoplasia. Using small-molecule drug-design approaches, we generated validated PXS-5505, first-in-class highly selective potent pan-lysyl inhibitor. We demonstrate vitro vivo that inhibition decreases chemotherapy-induced pancreatic desmoplasia stiffness, reduces cancer cell invasion metastasis,...
In prostate cancer, cancer-associated fibroblasts (CAF) exhibit contrasting biological properties to non-malignant (NPF) and promote tumorigenesis. Resolving intercellular signaling pathways between CAF tumor epithelium may offer novel opportunities for research translation. To this end, the proteome phosphoproteome of four pairs patient-matched NPF were characterized identify discriminating proteomic signatures. Samples analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
Understanding the underlying mechanisms of migration and metastasis is a key focus cancer research. There an urgent need to develop in vitro 3D tumor models that can mimic physiological cell-cell cell-extracellular matrix interactions, with high reproducibility are suitable for throughput (HTP) drug screening. Here, we developed HTP bioprinted model using bespoke drop-on-demand bioprinting platform. This platform coupled tunable hydrogel systems enables (i) rapid encapsulation cells within...
Abstract In recent decades, the role of tumor biomechanics on cancer cell behavior at primary site has been increasingly appreciated. However, effect latter stages metastatic cascade, such as seeding secondary sites and outgrowth remains underappreciated. This work sought to address this in context triple negative breast (TNBC), a type known aggressively disseminate all disease progression. Using mechanically tuneable model systems, mimicking range stiffness's typically found within tumors,...
Intravital imaging guides a personalized medicine approach to target mechanoreciprocity in pancreatic cancer.
In vitro cell models have undergone a shift from 2D on glass slides to 3D that better reflect the native microenvironment. bioprinting promises progress field by allowing high-throughput production of reproducible cell-laden structures with high fidelity. The current stiffness range printable matrices surrounding cells mimic extracellular matrix environment remains limited. work presented herein aims expand stiffnesses utilizing four-armed polyethylene glycol maleimide-functionalized arms....
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,...
Regular exercise can reduce incidence and progression of breast cancer, but the mechanisms for such effects are not fully understood.
Abstract Background The use of in vitro cell cultures is a powerful tool for obtaining key insights into the behaviour and response cells to interventions normal disease situations. Unlike vivo settings, experiments allow fine‐tuned control range microenvironmental elements independently within an isolated setting. recent expansion three‐dimensional (3D) assays has created number representative tools study more physiologically 3D relevant microenvironment. Complex models that can...
To fully investigate cellular responses to stimuli and perturbations within tissues, it is essential replicate the complex molecular interactions local microenvironment of niches. Here, authors introduce Alginate-based tissue engineering (ALTEN), a biomimetic platform that allows ex vivo analysis explanted biopsies. This method preserves original characteristics source tissue's milieu, allowing multiple diverse cell types be maintained over an extended period time. As result, ALTEN enables...
Summary Understanding the underlying mechanisms of migration and metastasis is a key focus cancer research. There an urgent need to develop in vitro 3D tumor models that can mimic physiological cell-cell cell-extracellular matrix interactions, with high reproducibility are suitable for throughput (HTP) drug screening. Here, we developed HTP bioprinted model using bespoke drop-on-demand bioprinting platform. This platform coupled tunable hydrogel systems enables (i) rapid encapsulation cells...
Abstract Precision medicine for paediatric and adult cancers that includes drug sensitivity profiling, can identify effective therapies individual patients. However, obtaining adequate biopsy samples high-throughput (HTP) screening remains challenging, with tumours needing to be expanded in culture or patient-derived xenografts – this is time-consuming often unsuccessful. Herein, we have developed tumour models using an engineered extracellular matrix (ECM) tissue mimic hydrogel system HTP...
Abstract Childhood cancer patients with high-risk disease have poor prognosis. Therapies given to treat these are often highly toxic and determined empirically, exposing children damaging ineffective therapies. Precision medicine is a promising strategy for patients. However, tumor biopsies lack sufficient sample phenotypic drug screening, requiring cell expansion via primary culture or development of patient-derived xenograft models - slow process variable success rates. There an unmet need...
ABSTRACT The cellular and molecular basis of stromal cell recruitment, activation crosstalk in carcinomas is poorly understood, limiting the development targeted anti-stromal therapies. In mouse models triple negative breast cancer (TNBC), Hh ligand produced by neoplastic cells reprogrammed cancer-associated fibroblast (CAF) gene expression, driving tumor growth metastasis. Hh-activated CAFs upregulated expression FGF5 production fibrillar collagen, leading to FGFR FAK adjacent cells, which...
ABSTRACT Changes in gene regulation and expression govern orderly transitions from hematopoietic stem cells to terminally differentiated blood cell types. These are disrupted during leukemic transformation but knowledge of the regulatory changes underpinning this process is elusive. We hypothesised that identifying core networks healthy could provide insights into network alterations perturb state transitions. A heptad transcription factors (LYL1, TAL1, LMO2, FLI1, ERG, GATA2, RUNX1) bind...
Abstract Differentiation of stem cells embedded within the mammary epithelium is orchestrated by lineage-specifying transcription factors. Unlike well-defined luminal hierarchy, dissection basal lineage has been hindered a lack specific markers. Inhibitor 4 (ID4) basally-restricted helix-loop-helix (HLH) factor essential for development. Here we show that ID4 highly expressed in and decreases during myoepithelial differentiation. By integrating transcriptomic, proteomic, ChIP-sequencing...
In vitro cell models have undergone a shift from 2D on glass slides to 3D that better reflect the native microenvironment. bioprinting promises progress field by allowing high throughput production of reproducible cell-laden structures with fidelity. As this technology is relatively new, current stiffness range printable matrices surrounding cells mimics extracellular matrix environment remains limited. The work presented here aims expand stiffnesses utilising 4-armed polyethylene glycol...