Elisabetta Mueller, Ph.D.


GDDB
GENETICS OF DEVELOPMENT & DISEASE BRANCH
NIDDK, National Institutes of Health
Building 10 , Room 8D12B
10 Center Dr.
Bethesda, MD 20814
Tel: 301-594-6797
Fax: 301-402-4136
Email: elisabettam@mail.nih.gov

Elisabetta Mueller, Ph.D.

Research Statement:

The laboratory focuses on the molecular mechanisms controlling mesenchymal cell differentiation with particular emphasis on the process of adipogenesis. The nuclear receptor PPARgamma serves as a key regulatory protein in promoting fat cell differentiation and this function constitutes an important target for restoring insulin sensitivity in diabetic patients. The factors responsible for commitment to the fat cell lineage during embryonic development have not been identified yet. One of our laboratory’s immediate research goals is to characterize novel molecules that can influence the adipogenic specification process. In addition, current studies are designed to define the key transcriptional circuits that are involved in lipid accumulation, glucose utilization and insulin sensitization.


Selected Publications:
  1. Teng R, Gavrilova O, Suzuki N, Chanturiya T, Schimel D, Hugendubler L, Mammen S, Yver DR, Cushman SW, Mueller E, Yamamoto M, Hsu LL, Noguchi CT. Disrupted erythropoietin signalling promotes obesity and alters hypothalamus proopiomelanocortin production. Nat Commun. 2011 Nov 1;2:520.

  2. Meruvu S, Hugendubler L, Mueller E. Regulation of adipocyte differentiation by the zinc finger protein ZNF638. J Biol Chem. 2011 Jul 29;286(30):26516-23. Epub 2011 May 20.

  3. Bagattin A, Hugendubler L, Mueller E. Transcriptional coactivator PGC-1alpha promotes peroxisomal remodeling and biogenesis. Proc Natl Acad Sci U S A. 2010 Nov 23;107(47):20376-81. Epub 2010 Nov 8.

  4. Di Pietro N, Panel V, Hayes S, Bagattin A, Meruvu S, Pandolfi A, Hugendubler L, Fejes-Tóth G, Naray-Fejes-Tóth A, Mueller E. Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates adipocyte differentiation via forkhead box O1. Mol Endocrinol. 2010 Feb;24(2):370-80. Epub 2009 Dec 4.

  5. Skarulis MC, Celi FS, Mueller E, Zemskova M, Malek R, Hugendubler L, Cochran C, Solomon J, Chen C, Gorden P. Thyroid hormone induced brown adipose tissue and amelioration of diabetes in a patient with extreme insulin resistance. J Clin Endocrinol Metab. 2010 Jan;95(1):256-62. Epub 2009 Nov 6.

  6. Leslie DS, Dascher CC, Cembrola K, Townes MA, Hava DL, Hugendubler LC, Mueller E, Fox L, Roura-Mir C, Moody DB, Vincent MS, Gumperz JE, Illarionov PA, Besra GS, Reynolds CG, Brenner MB. Serum lipids regulate dendritic cell CD1 expression and function. Immunology. 2008 Nov;125(3):289-301. Epub 2008 Apr 28.

  7. Hong JH, Hwang ES, McManus MT, Amsterdam A, Tian Y, Kalmukova R, Mueller E, Benjamin T, Spiegelman BM, Sharp PA, Hopkins N, Yaffe MB. TAZ, a transcriptional modulator of mesenchymal stem cell differentiation. Science. 2005 Aug 12;309(5737):1074-8.

  8. Drori S, Girnun GD, Tou L, Szwaya JD, Mueller E, Xia K, Shivdasani RA, Spiegelman BM. Hic-5 regulates an epithelial program mediated by PPARgamma. Genes Dev. 2005 Feb 1;19(3):362-75.

  9. Smith MR, Manola J, Kaufman DS, George D, Oh WK, Mueller E, Slovin S, Spiegelman B, Small E, Kantoff PW. Rosiglitazone versus placebo for men with prostate carcinoma and a rising serum prostate-specific antigen level after radical prostatectomy and/or radiation therapy. Cancer. 2004 Oct 1;101(7):1569-74.

  10. Salma N, Xiao H, Mueller E, Imbalzano AN. Temporal recruitment of transcription factors and SWI/SNF chromatin-remodeling enzymes during adipogenic induction of the peroxisome proliferator-activated receptor gamma nuclear hormone receptor. Mol Cell Biol. 2004 Jun;24(11):4651-63.

  11. Burstein HJ, Demetri GD, Mueller E, Sarraf P, Spiegelman BM, Winer EP. Use of the peroxisome proliferator-activated receptor (PPAR) gamma ligand troglitazone as treatment for refractory breast cancer: a phase II study. Breast Cancer Res Treat. 2003 Jun;79(3):391-7.

  12. Gupta RA, Sarraf P, Mueller E, Brockman JA, Prusakiewicz JJ, Eng C, Willson TM, DuBois RN. Peroxisome proliferator-activated receptor gamma-mediated differentiation: a mutation in colon cancer cells reveals divergent and cell type-specific mechanisms. J Biol Chem. 2003 Jun 20;278(25):22669-77. Epub 2003 Feb 18.

  13. Girnun GD, Smith WM, Drori S, Sarraf P, Mueller E, Eng C, Nambiar P, Rosenberg DW, Bronson RT, Edelmann W, Kucherlapati R, Gonzalez FJ, Spiegelman BM. APC-dependent suppression of colon carcinogenesis by PPARgamma. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13771-6. Epub 2002 Oct 7.

  14. Mueller E, Drori S, Aiyer A, Yie J, Sarraf P, Chen H, Hauser S, Rosen ED, Ge K, Roeder RG, Spiegelman BM. Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms.J Biol Chem. 2002 Nov 1;277(44):41925-30. Epub 2002 Aug 27.

  15. Mueller E, Smith M, Sarraf P, Kroll T, Aiyer A, Kaufman DS, Oh W, Demetri G, Figg WD, Zhou XP, Eng C, Spiegelman BM, Kantoff PW. Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10990-5.

  16. Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM, Fletcher JA. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science. 2000 Aug 25;289(5483):1357-60.

  17. Zhou XP, Smith WM, Gimm O, Mueller E, Gao X, Sarraf P, Prior TW, Plass C, von Deimling A, Black PM, Yates AJ, Eng C. Over-representation of PPARgamma sequence variants in sporadic cases of glioblastoma multiforme: preliminary evidence for common low penetrance modifiers for brain tumour risk in the general population. J Med Genet. 2000 Jun;37(6):410-4.

  18. Hauser S, Adelmant G, Sarraf P, Wright HM, Mueller E, Spiegelman BM. Degradation of the peroxisome proliferator-activated receptor gamma is linked to ligand-dependent activation. J Biol Chem. 2000 Jun 16;275(24):18527-33.

  19. Sarraf P, Mueller E, Smith WM, Wright HM, Kum JB, Aaltonen LA, de la Chapelle A, Spiegelman BM, Eng C. Loss-of-function mutations in PPAR gamma associated with human colon cancer. Mol Cell. 1999 Jun;3(6):799-804.

  20. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S. Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6.

  21. Sarraf P, Mueller E, Jones D, King FJ, DeAngelo DJ, Partridge JB, Holden SA, Chen LB, Singer S, Fletcher C, Spiegelman BM. Differentiation and reversal of malignant changes in colon cancer through PPARgamma. Nat Med. 1998 Sep;4(9):1046-52.

  22. Mueller E, Sarraf P, Tontonoz P, Evans RM, Martin KJ, Zhang M, Fletcher C, Singer S, Spiegelman BM.Terminal differentiation of human breast cancer through PPAR gamma. Mol Cell. 1998 Feb;1(3):465-70.

  23. Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, Lowell BB, Spiegelman BM. Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest. 1998 Jan 1;101(1):1-9.

  24. Tontonoz P, Singer S, Forman BM, Sarraf P, Fletcher JA, Fletcher CD, Brun RP, Mueller E, Altiok S, Oppenheim H, Evans RM, Spiegelman BM. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):237-41.

  25. Saez E, Rutberg SE, Mueller E, Oppenheim H, Smoluk J, Yuspa SH, Spiegelman BM. c-fos is required for malignant progression of skin tumors. Cell. 1995 Sep 8;82(5):721-32.

  26. Hu E, Mueller E, Oliviero S, Papaioannou VE, Johnson R, Spiegelman BM. Targeted disruption of the c-fos gene demonstrates c-fos-dependent and -independent pathways for gene expression stimulated by growth factors or oncogenes. EMBO J. 1994 Jul 1;13(13):3094-103.

  27. Cochrane S, Bergoffen J, Fairweather ND, Müller E, Mostacciuolo ML, Monaco AP, Fischbeck KH, Haites NE. X linked Charcot-Marie-Tooth disease (CMTX1): a study of 15 families with 12 highly informative polymorphisms. J Med Genet. 1994 Mar;31(3):193-6.

  28. Müller E, Mostacciuolo ML, Micaglio G, Angelini C, Danieli GA. Further evidence of a duplication in 17p11.2 in families with recurrence of HMSN Ia (Charcot-Marie-Tooth neuropathy type Ia). Hum Genet. 1992 Nov;90(3):231-4.

  29. Mostacciuolo ML, Danieli GA, Trevisan C, Müller E, Angelini C. Epidemiology of spinal muscular atrophies in a sample of the Italian population. Neuroepidemiology. 1992;11(1):34-8.

  30. Kress W, Müller E, Kausch K, Kullmann F, Mostacciuolo ML, Rietschel M, Rotthauwe HW, Schmalenberger B, Siciliano G, Voit T, et al. Multipoint linkage mapping of the Emery-Dreifuss muscular dystrophy gene. Neuromuscul Disord. 1992;2(2):111-5. Review.

  31. Mostacciuolo ML, Müller E, Fardin P, Micaglio GF, Bardoni B, Guioli S, Camerino G, Danieli GA.X-linked Charcot-Marie-Tooth disease. A linkage study in a large family by using 12 probes of the pericentromeric region. Hum Genet. 1991 May;87(1):23-7.



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