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Mary Rose Loeken, PH.D.

TitleAssociate Professor of Medicine (Physiology)
InstitutionJoslin Diabetes Center
DepartmentMedicine
AddressJoslin Diabetes Center
Research Division
One Joslin Place
Boston MA 02215
Phone617/732-2525
Fax617/309-2650

 Mentoring 
 current student opportunities
Available: 01/02/12, Expires: 12/31/15

Pax3 is a member of a family of developmental regulators that are expressed in a tissue-specific fashion during embryonic development. Pax3 is required for development of the neural tube, neural crest, and skeletal muscle. Expression of Pax3 is regulated by energy metabolism. Therefore, excess glucose metabolism, such as occurs during diabetic pregnancy, inhibits expression of Pax3 and can lead to malformation of Pax3-dependent structures, especially neural tube defects. The focus of the research in the Loeken lab is to understand how Pax3 is regulated by energy metabolism, and how Pax3 regulates embryonic development. Student projects will employ embryonic stem cells (mouse and human) that can be differentiated to express Pax3, and mouse strains carrying mutant Pax3 alleles. Experiments will investigate: 1. Chromatin structure (histone methylation and acetylation patterns and DNA methylation) that regulates Pax3 expression, and how it is affected by energy metabolism. 2. Regulation of post-translational modification and turnover of p53 tumor suppressor protein by Pax3. 3. Regulation of glycolytic and oxidative fuel metabolism by Pax3 and p53.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Loeken MR. A new role for pancreatic insulin in the male reproductive axis. Diabetes. 2012 Jul; 61(7):1667-8.
    View in: PubMed
  2. Wang XD, Morgan SC, Loeken MR. Pax3 stimulates p53 ubiquitination and degradation independent of transcription. PLoS One. 2011; 6(12):e29379.
    View in: PubMed
  3. Wu Y, Viana M, Thirumangalathu S, Loeken MR. AMP-activated protein kinase mediates effects of oxidative stress on embryo gene expression in a mouse model of diabetic embryopathy. Diabetologia. 2012 Jan; 55(1):245-54.
    View in: PubMed
  4. Zabihi S, Loeken MR. Understanding diabetic teratogenesis: where are we now and where are we going? Birth Defects Res A Clin Mol Teratol. 2010 Oct; 88(10):779-90.
    View in: PubMed
  5. Chappell JH, Wang XD, Loeken MR. Diabetes and apoptosis: neural crest cells and neural tube. Apoptosis. 2009 Dec; 14(12):1472-83.
    View in: PubMed
  6. Loeken MR. How TGF-beta and PAX3 regulate suntanning. Pigment Cell Melanoma Res. 2009 Apr; 22(2):146-7.
    View in: PubMed
  7. Loeken MR. Challenges in understanding diabetic embryopathy. Diabetes. 2008 Dec; 57(12):3187-8.
    View in: PubMed
  8. Morgan SC, Lee HY, Relaix F, Sandell LL, Levorse JM, Loeken MR. Cardiac outflow tract septation failure in Pax3-deficient embryos is due to p53-dependent regulation of migrating cardiac neural crest. Mech Dev. 2008 Sep-Oct; 125(9-10):757-67.
    View in: PubMed
  9. Morgan SC, Relaix F, Sandell LL, Loeken MR. Oxidative stress during diabetic pregnancy disrupts cardiac neural crest migration and causes outflow tract defects. Birth Defects Res A Clin Mol Teratol. 2008 Jun; 82(6):453-63.
    View in: PubMed
  10. Waisbren SE, Bowles H, Hasan T, Zou KH, Emans SJ, Goldberg C, Gould S, Levine D, Lieberman E, Loeken M, Longtine J, Nadelson C, Patenaude AF, Quinn D, Randolph AG, Solet JM, Ullrich N, Walensky R, Weitzman P, Christou H. Gender differences in research grant applications and funding outcomes for medical school faculty. J Womens Health (Larchmt). 2008 Mar; 17(2):207-14.
    View in: PubMed
  11. Li R, Thorens B, Loeken MR. Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy. Diabetologia. 2007 Mar; 50(3):682-9.
    View in: PubMed
  12. Viana, M, Curley, M, and Loeken, MR. Involvement of Protein Kinase C in Diabetic Embryopathy. 66th Annual Meeting, American Diabetes Association. 2006.
  13. Wang F, Thirumangalathu S, Loeken MR. Establishment of new mouse embryonic stem cell lines is improved by physiological glucose and oxygen. Cloning Stem Cells. 2006; 8(2):108-16.
    View in: PubMed
  14. Loeken MR. Advances in understanding the molecular causes of diabetes-induced birth defects. J Soc Gynecol Investig. 2006 Jan; 13(1):2-10.
    View in: PubMed
  15. Morgan, SC and Loeken, MR. Neural Tube Defects Induced by Diabetic Pregnancy: What They Tell Us About Metabolic Regulation of Development. 3rd International Symposium on Neural Tube Defects. 2005.
  16. Loeken, MR and Thirumangalathu, S. Involvement of AMP Kinase in Diabetic Embryopathy. 65th Annual Meeting, American Diabetes Association. 2005.
  17. Li R, Chase M, Jung SK, Smith PJ, Loeken MR. Hypoxic stress in diabetic pregnancy contributes to impaired embryo gene expression and defective development by inducing oxidative stress. Am J Physiol Endocrinol Metab. 2005 Oct; 289(4):E591-9.
    View in: PubMed
  18. Loeken MR. Current perspectives on the causes of neural tube defects resulting from diabetic pregnancy. Am J Med Genet C Semin Med Genet. 2005 May 15; 135C(1):77-87.
    View in: PubMed
  19. Horal M, Zhang Z, Stanton R, Virkamäki A, Loeken MR. Activation of the hexosamine pathway causes oxidative stress and abnormal embryo gene expression: involvement in diabetic teratogenesis. Birth Defects Res A Clin Mol Teratol. 2004 Aug; 70(8):519-27.
    View in: PubMed
  20. King GL, Loeken MR. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol. 2004 Oct; 122(4):333-8.
    View in: PubMed
  21. Loeken MR. Free radicals and birth defects. J Matern Fetal Neonatal Med. 2004 Jan; 15(1):6-14.
    View in: PubMed
  22. Chang TI, Horal M, Jain SK, Wang F, Patel R, Loeken MR. Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects. Diabetologia. 2003 Apr; 46(4):538-45.
    View in: PubMed
  23. Chan BW, Chan KS, Koide T, Yeung SM, Leung MB, Copp AJ, Loeken MR, Shiroishi T, Shum AS. Maternal diabetes increases the risk of caudal regression caused by retinoic acid. Diabetes. 2002 Sep; 51(9):2811-6.
    View in: PubMed
  24. Hiramatsu Y, Sekiguchi N, Hayashi M, Isshiki K, Yokota T, King GL, Loeken MR. Diacylglycerol production and protein kinase C activity are increased in a mouse model of diabetic embryopathy. Diabetes. 2002 Sep; 51(9):2804-10.
    View in: PubMed
  25. Pani L, Horal M, Loeken MR. Polymorphic susceptibility to the molecular causes of neural tube defects during diabetic embryopathy. Diabetes. 2002 Sep; 51(9):2871-4.
    View in: PubMed
  26. Pani L, Horal M, Loeken MR. Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3- dependent development and tumorigenesis. Genes Dev. 2002 Mar 15; 16(6):676-80.
    View in: PubMed
  27. Fine EL, Horal M, Chang TI, Fortin G, Loeken MR. Evidence that elevated glucose causes altered gene expression, apoptosis, and neural tube defects in a mouse model of diabetic pregnancy. Diabetes. 1999 Dec; 48(12):2454-62.
    View in: PubMed
  28. Chang TI, Loeken MR. Genotoxicity and diabetic embryopathy: impaired expression of developmental control genes as a cause of defective morphogenesis. Semin Reprod Endocrinol. 1999; 17(2):153-65.
    View in: PubMed
  29. Cai J, Phelan SA, Hill AL, Loeken MR. Identification of Dep-1, a new gene regulated by the transcription factor Pax-3, as a marker for altered embryonic gene expression during diabetic pregnancy. Diabetes. 1998 Nov; 47(11):1803-5.
    View in: PubMed
  30. Phelan SA, Loeken MR. Identification of a new binding motif for the paired domain of Pax-3 and unusual characteristics of spacing of bipartite recognition elements on binding and transcription activation. J Biol Chem. 1998 Jul 24; 273(30):19153-9.
    View in: PubMed
  31. Hill AL, Phelan SA, Loeken MR. Reduced expression of pax-3 is associated with overexpression of cdc46 in the mouse embryo. Dev Genes Evol. 1998 May; 208(3):128-34.
    View in: PubMed
  32. Phelan SA, Ito M, Loeken MR. Neural tube defects in embryos of diabetic mice: role of the Pax-3 gene and apoptosis. Diabetes. 1997 Jul; 46(7):1189-97.
    View in: PubMed
  33. Reynet C, Kahn CR, Loeken MR. Expression of the gene encoding glycogen phosphorylase is elevated in diabetic rat skeletal muscle and is regulated by insulin and cyclic AMP. Diabetologia. 1996 Feb; 39(2):183-9.
    View in: PubMed
  34. Loeken, MR. Use of SV40 small t antigen as a model to understand expression of cell cycle-regulated genes. Rosselin G (ed.) Proceedings from the first international symposium on VIP, PACAP and related regulatory peptides. 1994; 527-536.
  35. Loeken MR. Multiple, distinct trans-activation functions are encoded by the simian virus 40 large T and small t antigens, only some of which require the 82-residue amino-terminal common domain. J Virol. 1993 Dec; 67(12):7684-9.
    View in: PubMed
  36. Loeken MR. Effects of mutation of the CREB binding site of the somatostatin promoter on cyclic AMP responsiveness in CV-1 cells. Gene Expr. 1993; 3(3):253-64.
    View in: PubMed
  37. Loeken MR. Simian virus 40 small t antigen trans activates the adenovirus E2A promoter by using mechanisms distinct from those used by adenovirus E1A. J Virol. 1992 Apr; 66(4):2551-5.
    View in: PubMed
  38. Bikel I, Loeken MR. Involvement of simian virus 40 (SV40) small t antigen in trans activation of SV40 early and late promoters. J Virol. 1992 Mar; 66(3):1489-94.
    View in: PubMed
  39. Oliver FJ, de la Rubia G, Feener EP, Lee ME, Loeken MR, Shiba T, Quertermous T, King GL. Stimulation of endothelin-1 gene expression by insulin in endothelial cells. J Biol Chem. 1991 Dec 5; 266(34):23251-6.
    View in: PubMed
  40. Ferber S, Gross DJ, Villa-Komaroff L, Danehy F, Vollenweider F, Meyer K, Loeken MR, Kahn CR, Halban PA. Heterogeneity of expression and secretion of native and mutant [AspB10]insulin in AtT20 cells. Mol Endocrinol. 1991 Mar; 5(3):319-26.
    View in: PubMed
  41. Loeken MR, Brady J. The adenovirus EIIA enhancer. Analysis of regulatory sequences and changes in binding activity of ATF and EIIF following adenovirus infection. J Biol Chem. 1989 Apr 15; 264(11):6572-9.
    View in: PubMed
  42. Loeken M, Bikel I, Livingston DM, Brady J. trans-activation of RNA polymerase II and III promoters by SV40 small t antigen. Cell. 1988 Dec 23; 55(6):1171-7.
    View in: PubMed
  43. Brady J, Loeken MR, Thompson M, Duvall J, Khoury G. Regulation of viral transcription units by SV40 T-antigen. Aloni Y (ed.) Molecular aspects of papova virus. 1987; 119-135.
  44. Loeken MR, Khoury G, Brady J. Stimulation of the adenovirus E2 promoter by simian virus 40 T antigen or E1A occurs by different mechanisms. Mol Cell Biol. 1986 Jun; 6(6):2020-6.
    View in: PubMed
  45. Loeken MR, Khalili K, Khoury G, Brady J. Evidence that polymerase II transcription requires interaction between proteins binding to control sequences. Botchan M, Grodzicker T, Sharp PA (eds.). Cancer cells: Vol. 4-DNA tumor viruses: Control of gene expression and replication. 1986; 189-195.
  46. Brady J, Loeken MR, Khoury G. Interaction between two transcriptional control sequences required for tumor-antigen-mediated simian virus 40 late gene expression. Proc Natl Acad Sci U S A. 1985 Nov; 82(21):7299-303.
    View in: PubMed
  47. Loeken MR, Channing CP. Direct evidence for de-novo synthesis of LH receptors in cultured pig granulosa cells in response to FSH. J Reprod Fertil. 1985 Mar; 73(2):343-51.
    View in: PubMed
  48. Brady J, Loeken MR, Khoury G. Transcriptional control sequences-binding factors require interaction for T-antigen-mediated SV40 late gene expression. Gluzman Y (ed.) Eukaryotic transcription: The role of cis-and trans-acting elements in initiation. 1985; 72-77.
  49. Loeken, MR. Effects of follicle stimulating hormone on maturation of cultured porcine granulosa cells [Ph.D. dissertation]. 1984.
  50. Channing CP, Loeken MR, Osteen KG, Atlas SJ. Intraovarian regulation of maturation of granulosa cells. De Brux J, Gantray JR (eds.) Clinical pathology of the endocrine ovary. 1984; 46-61.
  51. Loeken MR, Roth TF. Analysis of maternal IgG subpopulations which are transported into the chicken oocyte. Immunology. 1983 May; 49(1):21-8.
    View in: PubMed
  52. Loeken MR, Channing CP, D'Eletto R, Weiss G. Stimulatory effect of luteinizing hormone upon relaxin secretion by cultured porcine preovulatory granulosa cells. Endocrinology. 1983 Feb; 112(2):769-71.
    View in: PubMed
  53. Osteen KG, Loeken MR, Channing CP. Intraovarian control of granulosa cell luteinization. Endocrinol Exp. 1982 Nov; 16(3-4):301-9.
    View in: PubMed
  54. Loeken, MR. Analysis of different maternal IgG subpopulations which are transported into the chicken oocyte [M.S. dissertation]. 1980.
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