A5103003460- Lymphatic System and Diseases
- Angiogenesis and VEGF in Cancer
- Cancer Diagnosis and Treatment
- Sympathectomy and Hyperhidrosis Treatments
- Cancer Cells and Metastasis
- TGF-β signaling in diseases
- Cancer, Stress, Anesthesia, and Immune Response
- Chemokine receptors and signaling
- Vascular Tumors and Angiosarcomas
- Lymphatic Disorders and Treatments
- Axon Guidance and Neuronal Signaling
- Cutaneous Melanoma Detection and Management
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Diagnosis and Treatment of Venous Diseases
- Body Contouring and Surgery
- Neurogenesis and neuroplasticity mechanisms
- Hippo pathway signaling and YAP/TAZ
- Enzyme Production and Characterization
- Microbial Metabolites in Food Biotechnology
- Spinal Cord Injury Research
- Nerve injury and regeneration
- CNS Lymphoma Diagnosis and Treatment
- Hedgehog Signaling Pathway Studies
- Machine Learning in Bioinformatics
O'Brien Institute
2017-2025
The University of Melbourne
2011-2025
St Vincents Institute of Medical Research
2017-2025
St Vincent's Hospital
2019-2025
Ludwig Cancer Research
2006-2019
The Royal Melbourne Hospital
2006-2019
Peter MacCallum Cancer Centre
2010-2019
Stanford University
2004-2007
Monash University
2006
La Trobe University
2000-2005
Chronic stress induces signalling from the sympathetic nervous system (SNS) and drives cancer progression, although pathways of tumour cell dissemination are unclear. Here we show that chronic restructures lymphatic networks within around tumours to provide for escape. We VEGFC derived cells is required induce remodelling this depends on COX2 inflammatory macrophages. Pharmacological inhibition SNS blocks effect in vivo reduces metastasis preclinical models patients with breast cancer. These...
Vascular endothelial growth factor (VEGF)-D is a secreted glycoprotein that induces angiogenesis and lymphangiogenesis. It consists of central domain, containing binding sites for VEGF receptor-2 (VEGFR-2) VEGFR-3, N- C-terminal propeptides. from the cell as homodimers full-length form can be proteolytically processed to remove was recently shown, using adenoviral gene delivery, fully VEGF-D in vivo, whereas does not. To better understand these observations, we monitored effect processing on...
Abstract Lymph node metastasis, an early and prognostically important event in the progression of many human cancers, is associated with expression VEGF-D. Changes to lymph vasculature that occur during malignant may create a metastatic niche capable attracting supporting tumor cells. In this study, we sought characterize molecules expressed endothelium could represent therapeutic or prognostic targets. Differential mRNA profiling endothelial cells from nodes drained nonmetastatic primary...
Metastasis via the lymphatic vasculature is an important step in cancer progression. The formation of new vessels (lymphangiogenesis), or remodeling existing lymphatics, thought to facilitate entry and transport tumor cells into on distant organs. migration endothelial (LEC) toward guidance cues critical for lymphangiogenesis. While chemokines are known provide directional navigation migrating immune cells, their role mediating LEC during tumor-associated lymphangiogenesis not well defined....
As a consequence of secondary pathophysiological mechanisms elicited after spinal cord injury (SCI), oligodendrocytes die by waves apoptosis. This ultimately results in demyelination intact axons leading to loss their conducting properties. Preservation as few 5% 10% myelinated individual tracts can confer locomotor recovery. Thus, strategies aimed at rescuing mature ensheathing viable are likely be therapeutic significance. We report that leukemia inhibitory factor (LIF) prevent...
The signaling proteins and pathways involved in lymphatic endothelial cell migration are identified through a functional screen.
Abstract Objectives Lipedema, a poorly understood chronic disease of adipose hyper-deposition, is often mistaken for obesity and causes significant impairment to mobility quality-of-life. To identify molecular mechanisms underpinning lipedema, we employed comprehensive omics-based comparative analyses whole tissue, adipocyte precursors (adipose-derived stem cells (ADSCs)), adipocytes from patients with or without lipedema. Methods We compared whole-tissues, ADSCs, body mass index–matched...
Kaposi’s sarcoma herpesvirus (KSHV) is the etiologic agent of (KS), a hyperplasia consisting enlarged malformed vasculature and spindle-shaped cells, main proliferative component KS. While spindle cells express markers lymphatic blood endothelium, origin unknown. Endothelial precursor have been proposed as source cells. We previously identified two types circulating endothelial colony forming (ECFCs), ones that expressed endothelium endothelium. Here we examined both ECFCs infected with...
Secondary lymphedema is a debilitating chronic tissue swelling in limb caused by inadequate interstitial fluid drainage due to dysfunctional lymphatic vessels. Pathological enlargement of small lymphatics contributes dysfunction secondary lymphedema, but molecular mechanisms driving this remodeling are unclear. Here, using surgical mouse model and whole-genome microarray, we identified the transcript for insulin-like growth factor binding protein 5 (IGFBP5), negative regulator (IGF)...
Important prognostic factors in patients with cutaneous melanoma include primary tumour thickness/depth of invasion, ulceration and mitotic rate, the presence cells regional lymph nodes. More recently, features stromal components, such as blood lymphatic vessel density, have been suggested additional indicators metastatic potential. Our aim was to investigate relationship between vessels node metastasis.Metastasizing (n = 11) non-metastasizing samples matched for depth/thickness, rate were...
Mutations in SOX18, VEGFC and Vascular Endothelial Growth Factor 3 underlie the hereditary lymphatic disorders hypotrichosis-lymphedema-telangiectasia (HLT), Milroy-like lymphedema Milroy disease, respectively. Genes responsible for are key regulators of vascular development embryo. To identify novel modulators lymphangiogenesis, we used a mouse model HLT (Ragged Opossum) performed gene expression profiling aberrant dermal vessels. Expression studies functional analysis zebrafish mice...
Introduction: Surgery and radiotherapy are key cancer treatments the leading causes of damage to lymphatics, a vascular network critical fluid homeostasis immunity. The clinical manifestation this constitutes devastating side-effect treatment, known as lymphoedema. Lymphoedema is chronic condition evolving from accumulation interstitial due impaired drainage via lymphatics recognised contribute significant morbidity patients who survive their cancer. Nevertheless, molecular mechanisms...
The crdS gene of Agrobacterium sp. strain ATCC31749 encodes the curdlan synthase (CrdS) protein based on homology derived CrdS sequence with those β-glycosyl transferases repetitive action patterns (Stasinopoulos et al. [1999] Glycobiology, 9, 31–41). Here we show that chemical (NTG) mutagenesis abolishes production and induced mutations can be complemented by a cloned amplicon, thus providing genetic confirmation is essential for production. When expressed in native or Escherichia coli,...
The lymphatic vasculature is critical for immunity and interstitial fluid homeostasis, playing important roles in diseases such as lymphedema metastatic cancer. Animal models have been generated to explore the role of lymphatics lymphangiogenic growth factors diseases, study development. However, analysis vessels has primary restricted counting two-dimensional tissue slices, due a lack more sophisticated methodologies. In order accurately examine dysfunction these models, analyse effects on...
VEGF-D is a mitogen for endothelial cells that promotes tumor growth and metastatic spread in animal models, expression of which correlates with lymph node metastasis some human cancers. It secreted from the cell as full-length form propeptides flanking central region containing binding sites VEGFR-2 VEGFR-3, receptors signal angiogenesis lymphangiogenesis. The can be cleaved VEGF-D, enhancing affinity VEGFR-3 vitro; however, importance this processing cancer unclear. To explore necessity...