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profileMary 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
vCardDownload vCard (login for email)

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Available: 07/01/17, Expires: 12/31/18

Diabetic pregnancy significantly increases risk for birth defects, especially neural tube and cardiac defects. The Loeken lab uses a mouse model of diabetic pregnancy and mouse and human pluripotent stem cells to study the biochemical and molecular mechanisms by which increased glucose metabolism by embryos alters gene expression, leading to cell death and congenital malformations. Student projects will employ mouse embryonic stem cells and human induced pluripotent stem cells that can be differentiated to neuronal precursors. Experiments will investigate: 1. Regulation of chromatin structure (histone methylation and acetylation patterns and DNA methylation) by glucose metabolism surrounding genes that control neuroepithelial differentiation. 2. Regulation of pluripotency vs. differentiated gene expression by glycolytic and oxidative fuel metabolism. 3. Effects of increased glucose uptake on self-renewal by early embryo and pluripotent stem cells.


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The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
R01DK104649     (LOEKEN, MARY R)Apr 1, 2015 - Jan 31, 2019
NIH/NIDDK
Role of Slc2a2/Glut2 in Embryo and Stem Cell Metabolism, Self-Renewal, and Pathways Involved in Diabetic Embryopathy
Role: Principal Investigator

R01DK058300     (LOEKEN, MARY R)Sep 1, 2000 - Mar 31, 2015
NIH/NIDDK
Embryonic Gene Expression During Diabetic Embryopathy
Role: Principal Investigator

R01DK052865     (LOEKEN, MARY R)Aug 1, 1998 - Feb 28, 2014
NIH/NIDDK
Search for the Molecular Causes of Diabetic Embryopathy
Role: Principal Investigator

R01CA050599     (LOEKEN, MARY R)Jul 1, 1992 - Apr 30, 1997
NIH/NCI
TRANSCRIPTION REGULATION BY SV40 SMALL T
Role: Principal Investigator

F32DK007078     (LOEKEN, MARY R)Jun 23, 1986
NIH/NIDDK
CEREBRAL HEMODYNAMICS IN THE STROKE-PRONE
Role: Principal Investigator

Collapse Bibliographic 
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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.
List All   |   Timeline
  1. Lindsay RS, Loeken MR. Metformin use in pregnancy: promises and uncertainties. Diabetologia. 2017 Sep; 60(9):1612-1619. PMID: 28770325.
    View in: PubMed
  2. Loeken MR. Passive smoking as an independent risk factor for gestational diabetes that synergizes with prepregnancy obesity in urban Chinese women. Diabetes Metab Res Rev. 2017 Sep; 33(6). PMID: 28580761.
    View in: PubMed
  3. Loeken MR. Importance of long-term care of diabetic women starting in pregnancy. Diabetes Metab Res Rev. 2017 Sep; 33(6). PMID: 28486767.
    View in: PubMed
  4. Egan AM, Galjaard S, Maresh MJA, Loeken MR, Napoli A, Anastasiou E, Noctor E, de Valk HW, van Poppel M, Todd M, Smith V, Devane D, Dunne FP. A core outcome set for studies evaluating the effectiveness of prepregnancy care for women with pregestational diabetes. Diabetologia. 2017 Jul; 60(7):1190-1196. PMID: 28409213.
    View in: PubMed
  5. Jung JH, Iwabuchi K, Yang Z, Loeken MR. Embryonic Stem Cell Proliferation Stimulated By Altered Anabolic Metabolism From Glucose Transporter 2-Transported Glucosamine. Sci Rep. 2016 Jun 17; 6:28452. PMID: 27311888; PMCID: PMC4911601.
  6. Loeken MR. Opportunities and challenges for repair of macrovascular disease using circulating blood-derived progenitor cells. Diabetes Metab Res Rev. 2014 Oct; 30(7):554-5. PMID: 25315433; PMCID: PMC4222573.
  7. Sanders K, Jung JH, Loeken MR. Use of a murine embryonic stem cell line that is sensitive to high glucose environment to model neural tube development in diabetic pregnancy. Birth Defects Res A Clin Mol Teratol. 2014 Aug; 100(8):584-91. PMID: 25124397; PMCID: PMC4220291.
  8. Wei D, Loeken MR. Increased DNA methyltransferase 3b (Dnmt3b)-mediated CpG island methylation stimulated by oxidative stress inhibits expression of a gene required for neural tube and neural crest development in diabetic pregnancy. Diabetes. 2014 Oct; 63(10):3512-22. PMID: 24834974; PMCID: PMC4171658.
  9. Loeken MR. Intersection of complex genetic traits affecting maternal metabolism, fetal metabolism, and neural tube defect risk: looking for needles in multiple haystacks. Mol Genet Metab. 2014 Apr; 111(4):415-7. PMID: 24503137; PMCID: PMC3982189.
  10. Lee HY, Wei D, Loeken MR. Lack of metformin effect on mouse embryo AMPK activity: implications for metformin treatment during pregnancy. Diabetes Metab Res Rev. 2014 Jan; 30(1):23-30. PMID: 23983188; PMCID: PMC3992340.
  11. Jung JH, Wang XD, Loeken MR. Mouse embryonic stem cells established in physiological-glucose media express the high KM Glut2 glucose transporter expressed by normal embryos. Stem Cells Transl Med. 2013 Dec; 2(12):929-34. PMID: 24167319; PMCID: PMC3841087.
  12. Loeken MR. A new role for pancreatic insulin in the male reproductive axis. Diabetes. 2012 Jul; 61(7):1667-8. PMID: 22723275; PMCID: PMC3379657.
  13. Wang XD, Morgan SC, Loeken MR. Pax3 stimulates p53 ubiquitination and degradation independent of transcription. PLoS One. 2011; 6(12):e29379. PMID: 22216266; PMCID: PMC3247257.
  14. 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. PMID: 21993711; PMCID: PMC3342033.
  15. 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. PMID: 20706996.
    View in: PubMed
  16. Chappell JH, Wang XD, Loeken MR. Diabetes and apoptosis: neural crest cells and neural tube. Apoptosis. 2009 Dec; 14(12):1472-83. PMID: 19333760.
    View in: PubMed
  17. Loeken MR. How TGF-beta and PAX3 regulate suntanning. Pigment Cell Melanoma Res. 2009 Apr; 22(2):146-7. PMID: 19207218.
    View in: PubMed
  18. Loeken MR. Challenges in understanding diabetic embryopathy. Diabetes. 2008 Dec; 57(12):3187-8. PMID: 19033406; PMCID: PMC2584122.
  19. 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. PMID: 18672055; PMCID: PMC2654333.
  20. 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. PMID: 18435457.
    View in: PubMed
  21. 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. PMID: 18321172.
    View in: PubMed
  22. 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. PMID: 17235524.
    View in: PubMed
  23. Viana, M, Curley, M, and Loeken, MR. Involvement of Protein Kinase C in Diabetic Embryopathy. 66th Annual Meeting, American Diabetes Association. 2006.
  24. 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. PMID: 16776602.
    View in: PubMed
  25. Loeken MR. Advances in understanding the molecular causes of diabetes-induced birth defects. J Soc Gynecol Investig. 2006 Jan; 13(1):2-10. PMID: 16303321.
    View in: PubMed
  26. 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.
  27. Loeken, MR and Thirumangalathu, S. Involvement of AMP Kinase in Diabetic Embryopathy. 65th Annual Meeting, American Diabetes Association. 2005.
  28. 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. PMID: 15928021.
    View in: PubMed
  29. 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. PMID: 15800853.
    View in: PubMed
  30. 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. PMID: 15329829.
    View in: PubMed
  31. King GL, Loeken MR. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol. 2004 Oct; 122(4):333-8. PMID: 15257460.
    View in: PubMed
  32. Loeken MR. Free radicals and birth defects. J Matern Fetal Neonatal Med. 2004 Jan; 15(1):6-14. PMID: 15101606.
    View in: PubMed
  33. 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. PMID: 12739027.
    View in: PubMed
  34. 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. PMID: 12196475.
    View in: PubMed
  35. 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. PMID: 12196474.
    View in: PubMed
  36. 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. PMID: 12196484.
    View in: PubMed
  37. 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. PMID: 11914272; PMCID: PMC155364.
  38. 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. PMID: 10580436.
    View in: PubMed
  39. 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. PMID: 10528366.
    View in: PubMed
  40. 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. PMID: 9792553.
    View in: PubMed
  41. 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. PMID: 9668101.
    View in: PubMed
  42. 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. PMID: 9601985.
    View in: PubMed
  43. 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. PMID: 9200655.
    View in: PubMed
  44. 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. PMID: 8635670.
    View in: PubMed
  45. 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.
  46. 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. PMID: 8230491; PMCID: PMC238242.
  47. 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. PMID: 7912577.
    View in: PubMed
  48. 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. PMID: 1532215; PMCID: PMC289057.
  49. 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. PMID: 1310761; PMCID: PMC240874.
  50. 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 05; 266(34):23251-6. PMID: 1744120.
    View in: PubMed
  51. 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. PMID: 1890988.
    View in: PubMed
  52. 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. PMID: 2522934.
    View in: PubMed
  53. 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. PMID: 3203384.
    View in: PubMed
  54. 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.
  55. 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. PMID: 3023915; PMCID: PMC367741.
  56. 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.
  57. 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. PMID: 2997782; PMCID: PMC391331.
  58. 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. PMID: 2985778.
    View in: PubMed
  59. 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.
  60. Loeken, MR. Effects of follicle stimulating hormone on maturation of cultured porcine granulosa cells [Ph.D. dissertation]. 1984.
  61. 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.
  62. Loeken MR, Roth TF. Analysis of maternal IgG subpopulations which are transported into the chicken oocyte. Immunology. 1983 May; 49(1):21-8. PMID: 6840806; PMCID: PMC1454086.
  63. 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. PMID: 6848371.
    View in: PubMed
  64. Osteen KG, Loeken MR, Channing CP. Intraovarian control of granulosa cell luteinization. Endocrinol Exp. 1982 Nov; 16(3-4):301-9. PMID: 6816575.
    View in: PubMed
  65. Loeken, MR. Analysis of different maternal IgG subpopulations which are transported into the chicken oocyte [M.S. dissertation]. 1980.
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