Helen WilliamsWestmead Hospital | SWAHS · Department of Surgery
Helen Williams
PhD
About
40
Publications
20,528
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Introduction
After completing my PhD in obesity at the University of Sydney in 2011, I started working on cardiovascular disease at Westmead Hospital. My current projects focus on the roles of monocyte and macrophage subsets in cardiovascular disease and related conditions. Though we sometimes collaborate to look at these cells in unrelated conditions as well! I work part time and spend my non-work time with my two young sons.
Education
March 2007 - November 2011
March 2003 - November 2006
Publications
Publications (40)
The three subsets of human monocytes, classical, intermediate, and nonclassical, show phenotypic heterogeneity, particularly in their expression of CD14 and CD16. This has enabled researchers to delve into the functions of each subset in the steady state as well as in disease. Studies have revealed that monocyte heterogeneity is multi-dimensional....
Monocytes play a key role in cardiovascular disease (CVD) as their influx into the vessel wall is necessary for the development of an atherosclerotic plaque. Monocytes are, however, heterogeneous differentiating from classical monocytes through the intermediate subset to the nonclassical subset. While it is recognized that the percentage of interme...
Hypertrophic scars (HTS) remain a common outcome of burn injury, particularly in children. They can arise from variations in the wound healing stages, such as an excessive inflammatory response or inefficient remodelling. Of the cells contributing to these healing stages, macrophages and fibrocytes are crucial. Specifically, the inflammatory phase...
The retention of low-density lipoprotein (LDL) is a key process in the pathogenesis of atherosclerosis, and largely mediated via smooth muscle cell-derived extracellular proteoglycans including the glycosaminoglycan chains. Macrophages can also internalize lipids via complexes with proteoglycans. However, the role of polarized macrophage-derived pr...
Dyslipidemia promotes development of the atherosclerotic plaques that characterise cardiovascular disease. Plaque progression requires the influx of monocytes into the vessel wall, but whether dyslipidemia is associated with an increased potential of monocytes to extravasate is largely unknown. Here (using flow cytometry) we examined recruitment ma...
Background:
While many risk factors for preeclampsia, such as increased body mass index, advanced maternal age, chronic hypertension, diabetes, are now established in clinical practice, maternal lipid profile has not been included in the risk assessment for preeclampsia. We aim to characterize the serum levels of Total Cholesterol (TC), High densi...
Objective:
Circulating levels of the anti-angiogenic factors sFlt-1 and sEndoglin are elevated in preeclampsia (PE) and fetal growth restriction (FGR), mainly secreted from placental trophoblast. This study aims to identify the contributory role of monocyte Flt-1 and endoglin expression in PE and FGR.
Study design:
A prospective cross-sectional...
Background
There is little available data on fetal monocyte phenotype and function. A prospective cross-sectional pilot study was conducted to describe the cord blood monocyte subset phenotype in preeclampsia (PE) and fetal growth restriction (FGR) as compared to normal pregnancy and maternal circulation.
Methods
Maternal and cord blood samples fr...
Monocytes are key contributors in various inflammatory disorders and alterations to these cells, including their subset proportions and functions, can have pathological significance. An ideal method for examining alterations to monocytes is whole blood flow cytometry as the minimal handling of samples by this method limits artifactual cell activati...
Aim:
Monocytes are likely to play a significant role in the pathogenesis of preeclampsia (PE) and intrauterine fetal growth restriction (IUGR), given their role in homeostasis and tissue repair. Our aim was to study the gestational changes in monocytes in normal pregnancy and to determine whether monocyte subsets and phenotype are altered in pregn...
Studies disrupting the chemokine pathway CX3CL1 (fractalkine)/ CX3CR1 have shown decreased atherosclerosis in animal models but the techniques used to interrupt the pathway have not been easily translatable into human trials. DNA vaccination potentially overcomes the translational difficulties. We evaluated the effect of a DNA vaccine, targeted to...
Results of readings of ELISA on anti-CX3CR1 antibody levels in serum at 2, 4 and 8 weeks after prime boost of CX3CR1 peptide and at the endpoint.
(XLSX)
Results of measurements of Serum IL-6, IL-12, CCL2, TNF-α, TFN-γ or IL-10 levels.
(XLSX)
Results of measurements of total serum cholesterol levels in ApoE-/- mice compared to WT C57/BL6 mice.
(XLSX)
Results of measurements of lipid deposition (% in plaque) in brachiocephalic arteries.
(XLSX)
Results of measurements of macrophage content (% in plaque) in brachiocephalic arteries.
(XLSX)
Results of measurements of area (in %) of plaque formation vs lumen and vessel wall in brachiocephalic arteries and aortic arch.
(XLSX)
Results of measurements of M1 and M2 macrophage content (% in plaque) in brachiocephalic arteries.
(XLSX)
Results of measurements of α-Smooth Muscle Actin (% in plaque) in brachiocephalic arteries.
(XLSX)
Background and aims
Atherogenesis is dependent upon monocyte influx into the vessel wall. In humans, three monocyte subsets exist, the number and function of which are significantly altered in cardiovascular disease (CVD). Whether such alterations arise in individuals with a perturbed lipid profile remains largely unanswered, but is important to de...
Increasing evidence shows that CC-chemokines promote inflammatory-driven angiogenesis, with little to no effect on hypoxia-mediated angiogenesis. Inhibition of the CC-chemokine class may therefore affect angiogenesis differently depending on the pathophysiological context. We compared the effect of CC-chemokine inhibition in inflammatory and physio...
Background: Atherosclerosis is characterised by formation of an inflamed-lipid and macrophage rich lesion within an arterial wall. There are two extremes forms of macrophages: the M1, which destroy tissue and the M2, which have a healing role. As such, M1 macrophages promote an unstable lesion, while M2 macrophages produce stabilising extracellular...
Background:
Specific monocyte and macrophage subsets have been implicated in atherosclerosis, with intermediate monocytes proportionally elevated in cardiovascular disease and M1 macrophages abundant in unstable atherosclerotic plaques. While several studies have shown altered proportions of these subsets in atherosclerosis, studies examining func...
Introduction: Macrophages are a key player in the pathogenesis of atherosclerosis. One way in which they contribute to plaque development is by production of extracellular matrix proteoglycans (PGs) which bind and retain apolipoprotein B within the vessel wall. However, macrophages differentiate into a range of different subsets in response to stim...
Pediatric burns remain a common injury after which many patients develop a severe form of scarring known as hypertrophic scarring. The formation of the hypertrophic scar arises from excessive production of collagen during wound healing. Wound repair and regeneration represents a complex process that is accomplished through many biological processes...
Expression profile of adhesion and chemokine markers on monocyte subsets and their association with Atherosclerosis
Introduction
Monocytes can differentiate into various macrophage phenotypes in health and disease, however the phenotype and polarisation of monocytes in pregnancies complicated by preeclampsia and intrauterine growth retardation has not yet been fully characterised.
Objectives
To determine if monocyte phenotype and polarization is altered in preg...
Whether an atherosclerotic plaque progresses and eventually ruptures is heavily influenced by the function of macrophages. However, it is clear that a spectrum of macrophage phenotypes is present in the plaque, with some exhibiting stabilizing functions. While macrophages expressing characteristic M1 and M2 markers are evident, the disparate microe...
The emerging understanding of macrophage subsets and their functions in the atherosclerotic plaque has led to the consensus that M1 macrophages are pro-atherogenic while M2 macrophages may promote plaque stability, primarily though their tissue repair and anti-inflammatory properties. As such, modulating macrophage function to promote plaque stabil...
Polarisation of monocyte subsets to an M1 phenotype in atherosclerosis
Williams H, Cassorla G, Pertsoulis N, Marmash N, Patel V, Hitos K, Fletcher J and Medbury H
VBRC, Department of Surgery, University of Sydney, Westmead Hospital, NSW
Aim: Intermediate monocytes are thought to be important in atherosclerosis because of their small, but signific...
Krüppel-like Factor 3 (KLF3) is a transcriptional regulator that we have shown to be involved in the regulation of adipogenesis in vitro. Here we report that KLF3 null mice are lean and protected from diet-induced obesity and glucose intolerance. On a chow diet, plasma levels of leptin are decreased, and adiponectin is increased. Despite significan...
Fat Aussie mice (foz/foz) are morbidly obese, glucose intolerant and have liver steatosis that develops into steatohepatitis on a high-fat diet. The cannabinoid 1 receptor (CB1) antagonist SR141716 has been shown to improve obesity-associated metabolic complications in humans and rodent models. The aim of this study was to assess the effect of SR14...
Questions
Question (1)
Our group has used LPS to induce the production of inflammatory cytokines (IL-1b, IL-6 and TNFalpha) in whole blood. We're interested to do these experiments using OxLDL and IFNgamma to induce the cytokine production, but have not found many references to indicate timing/concentrations we could use. If anyone can recommend some protocols or papers, that would be great.
Thanks!
