A5034982360- Multiple Myeloma Research and Treatments
- Bone health and treatments
- Cancer, Lipids, and Metabolism
- Prostate Cancer Treatment and Research
- Hematological disorders and diagnostics
- Ubiquitin and proteasome pathways
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Hypoxia, and Metabolism
- Cancer Treatment and Pharmacology
- Bone and Joint Diseases
- Cancer Cells and Metastasis
- RNA modifications and cancer
- Cytokine Signaling Pathways and Interactions
- Heat shock proteins research
- Adipokines, Inflammation, and Metabolic Diseases
- Testicular diseases and treatments
- Regulation of Appetite and Obesity
- Autophagy in Disease and Therapy
- Protease and Inhibitor Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Nuclear Structure and Function
- Oral health in cancer treatment
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
- Biomarkers in Disease Mechanisms
University College London Hospitals NHS Foundation Trust
2025
University College London
2025
University of Oxford
2015-2024
Nuffield Orthopaedic Centre
2015-2024
ORCID
2021
Oxford BioMedica (United Kingdom)
2019
Ludwig Cancer Research
2015
Ludwig Cancer Research
2014
Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident of microenvironment to drive disease progression development an osteolytic disease. Bone adipocytes (BMAds) are emerging as having important endocrine functions can support cell growth survival. However, how BMAds respond infiltrating tumor remains poorly understood. Using C57BL/KaLwRij murine model myeloma, adiposity was found be increased early stage localizing along tumor-bone...
The spread of cancer to bone is invariably fatal, with complex cross-talk between tumor cells and the microenvironment responsible for driving disease progression. By combining in silico analysis patient datasets metabolomic profiling prostate cultured cells, we demonstrate changing energy requirements microenvironment, identifying pentose phosphate pathway (PPP) as elevated metastasis, increased expression PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD) associated a...
Abstract Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced destruction are poorly understood current therapies do not restore lost mass. Using transcriptomic profiling of isolated lining cell subtypes from a murine model, we find morphogenetic protein (BMP) signalling upregulated in stromal progenitor cells. BMP has previously been reported to be dysregulated disease. Inhibition...
Adipocytes are a significant component of the bone marrow microenvironment. Although adipocytes were first identified more than 100 years ago, it is only in recent that an understanding their complex physiological role emerging. Bone act as local regulators skeletal biology and homeostasis, with studies suggesting adipose tissue metabolically active, can function endocrine organ. As such, have potential to interact tumour cells, influencing both growth disease. This review discusses current...
Multiple myeloma (MM) is an incurable hematologic cancer where malignant plasma cells accumulate in the bone marrow (BM), with disease progression highly dependent on cellular interactions. Obesity a major risk factor for myeloma, however underlying mechanisms are unclear. Here we used murine model to show that high cholesterol diet increases local and circulating levels of low density lipoprotein (LDL), increasing tumour burden vivo. Exogenous LDL induced bortezomib-specific drug resistance...
Tumor induction data in the mouse skin initiation-promotion system were found to be consistent with a quadratic function where coefficient of linear term depended on dose promoter. The model implies that existence promoters may more important at low doses carcinogen than high most testing is performed. Experiments are described showing initiating effect carcinogenic chemicals, such as benzo(a)pyrene, 7,12-dimethyl-benz(a)anthracene, nitroquinoline oxide and beta-propiolactone, accumulates...
Abstract One of the major challenges in prostate cancer (PCa) research is identification key players that control progression primary cancers to invasive and metastatic disease. The majority PCa express wild-type p53, whereas loss p63 expression, a p53 family member, common event. Here we identify inhibitor apoptosis-stimulating protein (iASPP), cellular regulator p63, as an important player progression. Detailed analysis epithelium iASPP transgenic mice, Δ8/Δ8 revealed deficiency resulted...
Abstract Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality life and clinical outcomes. Eliglustat, a U.S. Food Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven loss in preclinical vivo models myeloma. In combination zoledronic acid, bisphosphonate treats myeloma disease, eliglustat provided further protection from loss. Autophagic degradation TRAF3, key...
Multiple myeloma is a haematological malignancy that dependent upon interactions within the bone microenvironment to drive tumour growth and osteolytic disease. Metformin an anti-diabetic drug has attracted attention due its direct antitumor effects, including anti-myeloma properties. However, impact of on response metformin in unknown. We have employed vitro vivo models dissect out effects subsequent indirect response. demonstrate how treatment preosteoblasts increases cell attachment....
// Clare Verrill 1,2 , Lucia Cerundolo 2 Chad Mckee 3 Michael White 4 Christiana Kartsonaki 5 Eve Fryer 1 Emma Morris 2,4 Simon Brewster 6 Indrika Ratnayaka Luke Marsden Hans Lilja 2,7,8,9 Ruth Muschel Xin Lu Freddie Hamdy and Richard J. Bryant Department of Cellular Pathology, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, UK Nuffield Surgical Sciences, CRUK/MRC Institute for Radiation Oncology, Ludwig Cancer Research Ltd, Clinical Medicine,...
Abstract Multiple myeloma (MM) is a fatal hematological malignancy, where the majority of patients are diagnosed with, or develop, destructive and debilitating osteolytic bone lesions. Current treatments for MM disease such as bisphosphonate zoledronic acid can result in deleterious side effects at high doses. In this study, eliglustat, an FDA approved glycosphingolipid inhibitor, was shown to reduce preclinical models MM. Mechanistically, eliglustat alters lipid composition plasma membrane...