A5019231390- Estrogen and related hormone effects
- Neuropeptides and Animal Physiology
- Reproductive System and Pregnancy
- Growth Hormone and Insulin-like Growth Factors
- Molecular Biology Techniques and Applications
- Cytokine Signaling Pathways and Interactions
- Hypothalamic control of reproductive hormones
- Adipose Tissue and Metabolism
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- interferon and immune responses
- Pituitary Gland Disorders and Treatments
- Ovarian cancer diagnosis and treatment
- Endometriosis Research and Treatment
- Birth, Development, and Health
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Cancer-related gene regulation
- Cancer Genomics and Diagnostics
- Regulation of Appetite and Obesity
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Retinoids in leukemia and cellular processes
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- bioluminescence and chemiluminescence research
Imperial College London
2010-2019
Ovarian Cancer Action
2018
The London College
2017
Hammersmith Hospital
1988-2016
Addenbrooke's Hospital
2004
University of Cambridge
2004
King's College London
2004
The Honourable Society of Lincoln's Inn
1997-2001
London Postgraduate Medical and Dental Education
1988-1994
Harvard University Press
1992
Nuclear receptors and their coactivators have been shown to function as key regulators of adipose tissue biology. Here we show that a ligand-dependent transcriptional repressor for nuclear plays crucial role in regulating the balance between energy storage expenditure. Mice devoid corepressor protein RIP140 are lean, resistance high-fat diet-induced obesity hepatic steatosis, increased oxygen consumption. Although process adipogenesis is unaffected, expression certain lipogenic enzymes...
Human embryos frequently harbor large-scale complex chromosomal errors that impede normal development. Affected may fail to implant although many first breach the endometrial epithelium and embed in decidualizing stroma before being rejected via mechanisms are poorly understood. Here we show developmentally impaired human elicit an endoplasmic stress response decidual cells. A was also evident upon vivo exposure of mouse uteri culture medium conditioned by low-quality embryos. By contrast,...
Decidualization renders the endometrium transiently receptive to an implanting blastocyst although underlying mechanisms remain incompletely understood. Here we show that human endometrial stromal cells (HESCs) rapidly release IL-33, a key regulator of innate immune responses, upon decidualization. In parallel, differentiating HESCs upregulate IL-33 transmembrane receptor ST2L and other pro-inflammatory mediators before mounting profound anti-inflammatory response includes downregulation...
Nuclear receptor signaling plays an important role in energy metabolism. In this study we demonstrate that the nuclear corepressor RIP140 is a key regulator of metabolism skeletal muscle. expressed fiber type-specific manner, and manipulation its levels null, heterozygous, transgenic mice low promote while increased expression suppresses formation oxidative fibers. Expression profiling reveals global changes genes implicated both myofiber phenotype metabolic functions. Genes involved...
RNA-binding proteins (RBPs) are increasingly identified as post-transcriptional drivers of cancer progression. The RBP LARP1 is an mRNA stability regulator, and elevated expression the protein in hepatocellular lung cancers correlated with adverse prognosis. associates interactome that enriched for oncogenic transcripts. Here we explore role epithelial ovarian cancer, a disease characterized by rapid acquisition resistance to chemotherapy through induction pro-survival signalling. We show,...
Abstract Endocrine therapies target the activation of oestrogen receptor alpha (ERα) via distinct mechanisms, but it is not clear whether breast cancer cells can adapt to treatment using drug-specific mechanisms. Here we demonstrate that resistance emerges epigenetic reprogramming. Resistant display a spectrum phenotypical changes with invasive phenotypes evolving in lines resistant aromatase inhibitor (AI). Orthogonal genomics analysis reprogrammed regulatory regions identifies individual...
The current study evaluated three biomarkers [homologous recombination deficiency (HRD), tumor BRCA1/2 (tBRCA) mutations, and CCNE1 copy-number variation (CNV)] in ovarian tumors from patients enrolled on the SCOTROC4 clinical trial for associations with outcome following carboplatin monotherapy. Ovarian (n = 250), high-grade serous (HGSOC) subgroup analysis 179) were classified as HRD positive (HRD score ≥42 or tBRCA mutation) amplification (CCNE1 CNV >2.4). Seventy-four (30%) positive,...
Central and lateral hypothalamic concentrations of 10 regulatory peptides were measured by radioimmunoassay in streptozocin-induced diabetic (STZ-D) matched control rats between 1 day 14 wk after diabetes induction. After 2 wk, both central neuropeptide Y (NPY) STZ-D consistently higher than those found rats, with significant 30–50% increases at 4 the hypothalamus, 6 hypothalamus. Immunocytochemical studies 4- 6-wk animals showed appearance intensely NPY-positive swollen cell bodies...
The distributions of three novel peptides, 7B2, neuromedin B, and U, in rat, mouse, human pituitaries, rat hypothalamus, 30 pituitary tumors were investigated with immunocytochemistry. Immunoreactivity for 7B2 was present gonadotropes, intermediate lobe cells posterior nerve fibers rats mice, hypothalamus (particularly the median eminence), eight gonadotropinomas. In gonadectomized rats, larger, more numerous LHβ- 7B2-immunoreactive gonadotropes seen than controls. Extractable 7B2-like...
Abstract Purpose: CDK-activating kinase (CAK) is required for the regulation of cell cycle and a trimeric complex consisting cyclin-dependent 7 (CDK7), Cyclin H, accessory protein, MAT1. CDK7 also plays critical role in regulating transcription, primarily by phosphorylating RNA polymerase II, as well transcription factors such estrogen receptor-α (ER). Deregulation transcriptional control are general features tumor cells, highlighting potential use inhibitors novel cancer therapeutics....
Differentiation of human endometrial stromal cells (HESC) into decidual represents a highly coordinated process essential for embryo implantation. We show that decidualizing HESC down-regulate the histone methyltransferase enhancer Zeste homolog 2 (EZH2), resulting in declining levels trimethylation 3 on lysine 27 (H3K27me3) at proximal promoters key marker genes PRL and IGFBP1. Loss H3K27me3 was associated with reciprocal enrichment acetylation same residue, indicating active remodeling...
Abstract Approximately 30% of ERα breast cancer patients relapse with metastatic disease following adjuvant endocrine therapies. The connection between acquisition drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain undergoes epigenetic reprogramming in aromatase inhibitors (AI)-resistant cells, leading to Keratin-80 (KRT80) upregulation. KRT80 expression driven by de novo enhancer activation...
Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by RIA and immunocytochemistry in rat anterior pituitary gland. NPY prohormone messenger RNA (mRNA) identified Northern blot analysis. The possible regulation examined determining effects thyroid hormone manipulation on peptide synthesis. Three other neuropeptides, neurotensin (NT), substance P (SP), vasoactive intestinal (VIP), were studied for comparison. Hypothyroidism significantly...
Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues mediates estrogen induced binding. Here we demonstrate that plays a central role in regulating the transcriptional response epidermal growth (EGF) signaling. regulates subset EGF-ERα genes highly expressed aggressive tumours. Retrospective stratification luminal using protein levels primary further...
Aberrant transforming growth factor–β (TGF-β) signaling is a hallmark of the stromal microenvironment in cancer. Dickkopf-3 (Dkk-3), shown to inhibit TGF-β signaling, downregulated prostate cancer and upregulated stroma benign prostatic hyperplasia, but function Dkk-3 unclear. Here we show that DKK3 silencing WPMY-1 cells increases activity cell-conditioned media cell invasion Dkk-3-dependent manner. increased level cell-adhesion regulator TGF-β–induced protein (TGFBI) epithelial media,...
Galanin is widely distributed throughout the rat neural and endocrine system. The highest concentrations are found in anterior pituitary, it can influence classical pituitary hormone secretion. effects of manipulation on galanin content, mRNA, immunostaining have been investigated rat. In females, medical (39 +/- 4 fmol/gland), surgical (33 2), or combined (28 6) castration resulted a highly significant decrease content (control, 223 14; P less than 0.0001). Estrogen physiological...
Nuclear receptor interacting protein (Nrip1), also known as RIP140, is a co-regulator for nuclear receptors that plays an essential role in ovulation by regulating the expression of epidermal growth factor-like family factors. Although several studies indicate RIP140 breast cancer, its development mammary gland unclear. By using RIP140-null and transgenic mice, we demonstrate factor normal it functions mediating oestrogen signalling. mice exhibit minimal ductal elongation with no...