Imperial College London

ProfessorMalcolmParker

Faculty of MedicineDepartment of Surgery & Cancer

Emeritus Professor of Molecular Endocrinology
 
 
 
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Contact

 

+44 (0)20 7594 2177m.parker Website

 
 
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Assistant

 

Miss Kiran Dosanjh +44 (0)20 7594 2176

 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

196 results found

Barneda D, Planas-Iglesias J, Gaspar ML, Mohammadyani D, Prasannan S, Dormann D, Han GS, Jesch SA, Carman GM, Kagan V, Parker MG, Ktistakis NT, Klein-Seetharaman J, Dixon AM, Henry SA, Christian Met al., 2015, The brown adipocyte protein CIDEA promotes lipid droplet fusion via a phosphatidic acid-binding amphipathic helix., eLife, Vol: 4, ISSN: 2050-084X

Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD-LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.

Journal article

Nikolopoulou E, Papacleovoulou G, Jean-Alphonse F, Grimaldi G, Parker MG, Hanyaloglu AC, Christian Met al., 2014, Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential, Journal of Lipid Research, Vol: 55, Pages: 2479-2490, ISSN: 0022-2275

Arachidonic acid (AA) is a major PUFA that has been implicated in the regulation of adipogenesis. We examined the effect of a short exposure to AA at different stages of 3T3-L1 adipocyte differentiation. AA caused the upregulation of fatty acid binding protein 4 (FABP4/aP2) following 24 h of differentiation. This was mediated by the prostaglandin F2α (PGF2α), as inhibition of cyclooxygenases or PGF2α receptor signaling counteracted the AA-mediated aP2 induction. In addition, calcium, protein kinase C, and ERK are all key elements of the pathway through which AA induces the expression of aP2. We also show that treatment with AA during the first 24 h of differentiation upregulates the expression of the transcription factor Fos-related antigen 1 (Fra-1) via the same pathway. Finally, treatment with AA for 24 h at the beginning of the adipocyte differentiation is sufficient to inhibit the late stages of adipogenesis through a Fra-1-dependent pathway, as Fra-1 knockdown rescued adipogenesis. Our data show that AA is able to program the differentiation potential of preadipocytes by regulating gene expression at the early stages of adipogenesis.

Journal article

Rosell M, Nevedomskaya E, Stelloo S, Nautiyal J, Poliandri A, Steel JH, Wessels LFA, Carroll JS, Parker MG, Zwart Wet al., 2014, Complex Formation and Function of Estrogen Receptor alpha in Transcription Requires RIP140, CANCER RESEARCH, Vol: 74, Pages: 5469-5479, ISSN: 0008-5472

Journal article

Rosell M, Kaforou M, Frontini A, Okolo A, Chan Y-W, Nikolopoulou E, Millership S, Fenech ME, MacIntyre D, Turner JO, Moore JD, Blackburn E, Gullick WJ, Cinti S, Montana G, Parker MG, Christian Met al., 2014, Brown and white adipose tissues: intrinsic differences in gene expression and response to cold exposure in mice, AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, Vol: 306, Pages: E945-E964, ISSN: 0193-1849

Journal article

Kiskinis E, Chatzeli L, Curry E, Kaforou M, Frontini A, Cinti S, Montana G, Parker MG, Christian Met al., 2014, RIP140 Represses the "Brown-in-White" Adipocyte Program Including a Futile Cycle of Triacyclglycerol Breakdown and Synthesis, MOLECULAR ENDOCRINOLOGY, Vol: 28, Pages: 344-356, ISSN: 0888-8809

Journal article

Nautiyal J, Christian M, Parker M, 2013, Distinct functions of RIP140 in Development, Inflammation and Metabolism, Trends in Endocrinology and Metabolism

Journal article

Nautiyal J, Steel JH, Mane MR, Oduwole O, Poliandri A, Alexi X, Wood N, Poutanen M, Zwart W, Stingl J, Parker MGet al., 2013, The transcriptional co-factor RIP140 regulates mammary gland development by promoting the generation of key mitogenic signals, Development, Vol: 140, Pages: 1079-1089, ISSN: 0950-1991

Journal article

Percharde M, Lavial F, Ng J-H, Kumar V, Tomaz RA, Martin N, Yeo J-C, Gil J, Prabhakar S, Ng H-H, Parker MG, Azuara Vet al., 2012, Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming, GENES & DEVELOPMENT, Vol: 26, Pages: 2286-2298, ISSN: 0890-9369

Journal article

Abu-Hayyeh S, Papacleovoulou G, Lovgren-Sandblom A, Tahir M, Oduwole O, Jamaludin NA, Ravat S, Nikolova V, Chambers J, Selden C, Rees M, Marschall HU, Parker MG, Williamson Cet al., 2012, Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit FXR resulting in a pro-cholestatic phenotype, Hepatology

Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3alpha-sulfated progesterone metabolites have been shown to be elevated in ICP leading us to study the impact of sulfated progesterone metabolites on farnesoid x receptor (FXR) mediated bile acid homeostasis pathways. Here we report that the 3beta-sulfated progesterone metabolite epiallopregnanolone sulfate is supraphysiologically raised in the serum of ICP patients. Mice challenged with cholic acid developed hypercholanemia and a hepatic gene expression profile indicative of FXR activation. However, co-administration of epiallopregnanolone sulfate with cholic acid exacerbated the hypercholanemia and resulted in aberrant gene expression profiles for hepatic bile acid-responsive genes consistent with cholestasis. We demonstrate that levels of epiallopregnanolone sulfate found in ICP can function as a partial agonist for FXR,resulting in the aberrant expression of bile acid homeostasis genes in hepatoma cell lines and primary human hepatocytes. Furthermore, epiallopregnanolone sulfate inhibition of FXR results in reduced FXR-mediated bile acid efflux and secreted FGF19. Using co-factor recruitment assays, we show that epiallopregnanolone sulfate competitively inhibits bile acid-mediated recruitment of co-factor motifs to the FXR-ligand binding domain. Conclusion: Our results reveal a novel molecular interaction between ICP-associated levels of the 3beta-sulfated progesterone metabolite epiallopregnanolone sulfate and FXR that couples the endocrine component of pregnancy in ICP to abnormal bile acid homeostasis. (HEPATOLOGY 2012.)

Journal article

Fritah A, Steel JH, Parker N, Nikolopoulou E, Christian M, Carling D, Parker MGet al., 2012, Absence of RIP140 Reveals a Pathway Regulating glut4-Dependent Glucose Uptake in Oxidative Skeletal Muscle through UCP1-Mediated Activation of AMPK, PLOS ONE, Vol: 7, ISSN: 1932-6203

Journal article

Duclot F, Lapierre M, Fritsch S, White R, Parker MG, Maurice T, Cavailles Vet al., 2012, Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene expression, GENES BRAIN AND BEHAVIOR, Vol: 11, Pages: 69-78, ISSN: 1601-1848

Journal article

Rong Y, Meng Q, Nautiyal J, Flurkey K, Tsaih SW, Krier R, Parker M, Harrison DE, Paigen Bet al., 2012, Genetic co-regulation of age of female sexual maturation and life span through circulating IGF-1 among inbred mouse strains, Proceedings of the National Academy of Sciences

Journal article

Rosell M, Jones MC, Parker MG, 2011, Role of nuclear receptor corepressor RIP140 in metabolic syndrome, BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, Vol: 1812, Pages: 919-928, ISSN: 0925-4439

Journal article

Poliandri AHB, Gamsby JJ, Christian M, Spinella MJ, Loros JJ, Dunlap JC, Parker MGet al., 2011, Modulation of Clock Gene Expression by the Transcriptional Coregulator Receptor Interacting Protein 140 (RIP140), JOURNAL OF BIOLOGICAL RHYTHMS, Vol: 26, Pages: 187-199, ISSN: 0748-7304

Journal article

Abu-Hayyeh S, Papacleovoulou G, Tahir M, Parker MG, Williamson Cet al., 2010, SULPHATED PROGESTERONE METABOLITES ATTENUATE FXR FUNCTION, 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases, Publisher: WILEY-BLACKWELL, Pages: 480A-480A, ISSN: 0270-9139

Conference paper

Milona A, Owen BM, Cobbold JFL, Willemsen ECL, Cox IJ, Boudjelal M, Cairns W, Schoonjans K, Taylor-Robinson SD, Klomp LWJ, Parker MG, White R, van Mil SWC, Williamson Cet al., 2010, Raised Hepatic: Bile Acid Concentrations During Pregnancy in Mice Are Associated with Reduced Farnesoid X Receptor Function, HEPATOLOGY, Vol: 52, Pages: 1341-1349, ISSN: 0270-9139

Journal article

Nautiyal J, Steel JH, Rosell MM, Nikolopoulou E, Lee K, DeMayo FJ, White R, Richards JS, Parker MGet al., 2010, The Nuclear Receptor Cofactor Receptor-Interacting Protein 140 Is a Positive Regulator of Amphiregulin Expression and Cumulus Cell-Oocyte Complex Expansion in the Mouse Ovary, ENDOCRINOLOGY, Vol: 151, Pages: 2923-2932, ISSN: 0013-7227

Journal article

Morganstein DL, Wu P, Mane MR, Fisk NM, White R, Parker MGet al., 2010, Human fetal mesenchymal stem cells differentiate into brown and white adipocytes: a role for ERR alpha in human UCP1 expression, CELL RESEARCH, Vol: 20, Pages: 434-444, ISSN: 1001-0602

Journal article

Parker MG, Zschiedrich I, Herzig S, 2010, Diverse actions of the nuclear receptor corepressor RIP140 in metabolic regulation, ENDOCRINE JOURNAL, Vol: 57, Pages: S262-S262, ISSN: 0918-8959

Journal article

Christian M, Parker MG, 2010, The Engineering of Brown Fat, JOURNAL OF MOLECULAR CELL BIOLOGY, Vol: 2, Pages: 23-25, ISSN: 1674-2788

Journal article

Fritah A, Christian M, Parker MG, 2010, The metabolic coregulator RIP140: an update, Am J Physiol Endocrinol Metab, Vol: 299, Pages: E335-E340, ISSN: 1522-1555

RIP140 is a transcriptional coregulator highly expressed in metabolic tissues where it has important and diverse actions. RIP140-null mice show that it plays a crucial role in the control of lipid metabolism in adipose tissue, skeletal muscle, and the liver and is essential for female fertility. RIP140 has been shown to act as a ligand-dependent transcriptional corepressor for metabolic nuclear receptors such as estrogen-related receptors and peroxisome proliferator-activated receptors. The role of RIP140 as a corepressor has been strengthened by the characterization of RIP140-overexpressing mice, although it emerges through several studies that RIP140 can also behave as a coactivator. Nuclear localization of RIP140 is important for controlling transcription of target genes and is subject to regulation by posttranslational modifications. However, cytoplasmic RIP140 has been shown to play a role in the control of metabolism through direct regulation of glucose transport in adipocytes. In this review, we focus on recent advances highlighting the growing importance of RIP140 as a regulator of energy homeostasis.

Journal article

Ahlbory-Dieker DL, Stride BD, Leder G, Schkoldow J, Troelenberg S, Seidel H, Otto C, Sommer A, Parker MG, Schuetz G, Wintermantel TMet al., 2009, DNA Binding by Estrogen Receptor-alpha Is Essential for the Transcriptional Response to Estrogen in the Liver and the Uterus, MOLECULAR ENDOCRINOLOGY, Vol: 23, Pages: 1544-1555, ISSN: 0888-8809

Journal article

Brosens JJ, Parker MG, McIndoe A, Pijnenborg R, Brosens IAet al., 2009, A role for menstruation in preconditioning the uterus for successful pregnancy, AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, Vol: 200, ISSN: 0002-9378

Journal article

Hallberg M, Morganstein DL, Kiskinis E, Shah K, Kralli A, Dilworth SM, White R, Parker MG, Christian Met al., 2008, A Functional Interaction between RIP140 and PGC-1 alpha Regulates the Expression of the Lipid Droplet Protein CIDEA, MOLECULAR AND CELLULAR BIOLOGY, Vol: 28, Pages: 6785-6795, ISSN: 0270-7306

Journal article

Zschiedrich I, Hardeland U, Krones-Herzig A, Diaz MB, Vegiopoulos A, Mueggenburg J, Sombroek D, Hofmann TG, Zawatzky R, Yu X, Gretz N, Christian M, White R, Parker MG, Herzig Set al., 2008, Coactivator function of RIP140 for NF kappa B/RelA-dependent cytokine gene expression, BLOOD, Vol: 112, Pages: 264-276, ISSN: 0006-4971

Journal article

Brooke GN, Parker MG, Bevan CL, 2008, Mechanisms of androgen receptor activation in advanced prostate cancer: differential co-activator recruitment and gene expression, ONCOGENE, Vol: 27, Pages: 2941-2950, ISSN: 0950-9232

Journal article

White R, Morganstein D, Christian M, Seth A, Herzog B, Parker MGet al., 2008, Role of RIP140 in metabolic tissues: Connections to disease, FEBS LETTERS, Vol: 582, Pages: 39-45, ISSN: 0014-5793

Journal article

Ali S, Periyasamy M, Lopez-Garcia J, Thomas RS, Christian M, Parker MG, Buluwela Let al., 2008, ZNF366 is a novel corepressor for estrogen receptor alpha that mediates its effects through interaction with CtBP, Breast Cancer Research Meeting, Publisher: BIOMED CENTRAL LTD, Pages: S7-S7, ISSN: 1465-5411

Conference paper

Morganstein DL, Christian M, Turner JJ, Parker MG, White Ret al., 2008, Conditionally immortalized white preadipocytes: a novel adipocyte model, J Lipid Res, Vol: 49, Pages: 679-685, ISSN: 0022-2275

This study describes a novel approach to generate conditionally immortalized preadipocyte cell lines from white adipose tissue (IMWAT) that can be induced to differentiate into white adipocytes even after expansion in culture. Such adipocytes express markers of white fat such as peroxisome proliferator-activated receptor gamma and aP2 but not brown fat markers, have an intact insulin signaling pathway, and express proinflammatory cytokines. They can be readily transduced with adenoviral vectors, allowing them to be used to investigate the consequences of the depletion of specific adipocyte factors using short hairpin RNA. This approach has been used to study the effect of reduced expression of the nuclear receptor corepressor receptor interacting protein 140 (RIP140), a regulator of adipocyte function. The depletion of RIP140 results in changes in metabolic gene expression that resemble those in adipose tissue of the RIP140 null mouse. Thus, IMWAT cells provide a novel model for adipocytes that are derived from preadipocytes rather than fibroblasts and provide an alternative system to primary preadipocytes for the investigation of adipocyte function.

Journal article

Parker MG, Christian M, Kiskinis E, Seth A, Nichol D, White Ret al., 2008, Role of the RIP140 Corepressor in Metabolic Regulation, NR Coregulators and Human Disease, Editors: Kumar, O'Malley, Singapore, Publisher: World Scientific Publishing Ltd, Pages: 343-356

Book chapter

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