
Michaelia CockshellCentre for Cancer Biology | CCB · Department of Immunology
Michaelia Cockshell
B Sci (Biomedical Science), B Sci (Honours)
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38
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Publications
Publications (38)
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with a dismal 5-year survival rate of <13%. We have discovered that desmoglein-2 (DSG2), a cell surface protein, is highly expressed on PDAC cells. In silico data indicate that elevated levels of DSG2 is associated with PDAC progression and poor patient survival. Immuno...
Objectives
CAR‐T cells are being investigated as a novel immunotherapy for glioblastoma, but clinical success has been limited. We recently described fibroblast activation protein (FAP) as an ideal target antigen for glioblastoma immunotherapy, with expression on both tumor cells and tumor blood vessels. However, CAR‐T cells targeting FAP have neve...
While blood‐contacting materials are widely deployed in medicine in vascular stents, catheters, and cannulas, devices fail in situ because of thrombosis and restenosis. Furthermore, microbial attachment and biofilm formation is not an uncommon problem for medical devices. Even incremental improvements in hemocompatible materials can provide signifi...
Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To charact...
Cardiovascular disease is a leading cause of death worldwide; however, despite substantial advances in medical device surface modifications, no synthetic coatings have so far matched the native endothelium as the optimal hemocompatible surface for blood-contacting implants. A promising strategy for rapid restoration of the endothelium on blood-cont...
Synthetic materials with an innate ability to avoid the foreign-body-response remain an unrealized goal that would transform the medical device industry. The balance of bulk material properties, that enable a device to perform as intended, with surface properties, that provide bio- and hemocompatibility, has always required the former to be priorit...
The progression of cancer is facilitated by infiltrating leukocytes which can either actively kill cancer cells or promote their survival. Our current understanding of leukocyte recruitment into tumors is largely limited to the adhesion molecules and chemokines expressed by conventional blood vessels that are lined by endothelial cells (ECs). Howev...
The growth of solid tumours relies on an ever-increasing supply of oxygen and nutrients that are delivered via vascular networks. Tumour vasculature includes endothelial cell lined angiogenesis and the less common cancer cell lined vasculogenic mimicry (VM). To study and compare the development of vascular networks formed during angiogenesis and VM...
Background
The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as va...
Background: The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as v...
Hyperbranched polyglycerol (HPG) was previously investigated as a non-fouling hydrophilic grafted layer on biomaterials surfaces, analogous to the well-known PEO, but the range of adsorbing cells and proteins tested was limited and at times the assays used were not the most sensitive. Thus the questions arise whether HPG-grafted layers can indeed e...
Tumour vasculature supports the growth and progression of solid cancers with both angiogenesis (endothelial cell proliferation) and vasculogenic mimicry (VM, the formation of vascular structures by cancer cells themselves) predictors of poor patient outcomes. Increased circulating platelet counts also predict poor outcome for cancer patients but th...
Background and objective
Pulmonary arterial hypertension (PAH) is characterized by increased resistance in the distal pulmonary arteries, ultimately leading to right heart failure and, despite the available therapeutics, survival remains poor. Reduced expression of bone morphogenetic protein receptor type 2 (BMPR2) is strongly associated with PAH....
PolyJet three-dimensional (3D) printing allows for the rapid manufacturing of 3D moulds for the fabrication of cross-linked poly(dimethylsiloxane) microwell arrays (PMAs). As this 3D printing technique has a resolution on the micrometer scale, the moulds exhibit a distinct surface roughness. In this study, the authors demonstrate by optical profilo...
The propensity of glycosaminoglycans to mediate cell-cell and cell-matrix interactions opens the door to capture cells, including circulating blood cells, onto biomaterial substrates. Chondroitin sulfate (CS) -B is of particular interest, since it interacts with the receptor (EGF)-like module-containing mucin-like hormone receptor-like 2 precursor...
Porous silicon (pSi) substrates are a promising platform for cell expansion, since pore size and chemistry can be tuned to control cell behavior. In addition, a variety of bioactives can be loaded into the pores and subsequently released to act on cells adherent to the substrate. Here we construct a cell microarray on plasma polymer coated pSi subs...
Desmogleins (DSG) are a family of cadherin adhesion proteins that were first identified in desmosomes and provide cardiomyocytes and epithelial cells with the junctional stability to tolerate mechanical stress. However, one member of this family, DSG2, is emerging as a protein with additional biological functions on a broader range of cells. Here w...
Sphingosine 1-phosphate (S1P) is a bioactive lipid that can function both extracellularly and intracellularly to mediate a variety of cellular processes. Using lipid affinity matrices and a radiolabeled lipid binding assay, we reveal that S1P directly interacts with the transcription factor peroxisome proliferator-activated receptor (PPAR)gamma. He...
Although endothelial cell (EC) infection is not widespread during dengue virus (DENV) infection in vivo, the endothelium is the site of the pathogenic effects seen in severe DENV disease. In this study, we investigated DENV infection of primary EC and defined factors that influence infection in this cell type. Consistent with in vivo findings where...
Circulating endothelial progenitor cells (EPCs) provide revascularisation for cardiovascular disease and the expansion of these cells opens up the possibility of their use as a cell therapy. Herein we show that interleukin-3 (IL3) strongly expands a population of human non-adherent endothelial forming cells (EXnaEFCs) with low immunogenicity as wel...
Circulating vascular progenitor cells contribute to the pathological vasculogenesis of cancer whilst on the other hand offer much promise in therapeutic revascularization in post-occlusion intervention in cardiovascular disease. However, their characterization has been hampered by the many variables to produce them as well as their described phenot...
Surface expression profiling of early EPCs. Early EPCs were phenotyped for hematopoietic progenitor cell (CD117, CD34), endothelial cell (CD31, CD144) and leukocyte cell (CD45, CD11b, CD14) markers by flow cytometry. In the histograms, the light dotted lines represent unstained cells and the dark lines represent stained cells of one representative...
Surface expression profiling of naEFCs and PBMNCs. In (A), a representative dot plot of CD133+CD117+ double positive naEFCs were examined for CD41a surface expression by flow cytometry. The light dotted line represents the unstained control and the dark line represents cells stained for CD41a. One representative experiment is shown from n = 5. In (...
Parallel plate flow chamber video of HUVEC pre-treated without or with TNFα (5 ng/ml, 5 hours) prior to perfusion of naEFCs pre-treated with an isotype control (iso control) antibody or an ICAM-3 blocking antibody (1 µg, 30 min) at 2 dynes/cm2 for 5 minutes. Playback speed is 1×.
(MP4)
The use of endothelial progenitor cells in vascular therapies has been limited due to their low numbers present in the bone marrow and peripheral blood. The aim of this study was to investigate the effect of sphingosine kinase on the de-differentiation of mature human endothelial cells toward a progenitor phenotype.
The lipid enzyme sphingosine kin...
Adjuvant-induced arthritis can be transferred to naive Dark Agouti (DA) strain (DA.CD45.1) rats by thoracic duct (TD) lymphocytes.
Disease can be re-induced in convalescent rats by further transfer of arthritogenic cells, suggesting that resolution of the
adoptive disease is not due to active regulation. To examine whether resolution is due to exha...