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Last Name

profileAnn Marie Zavacki, PH.D.

TitleAssistant Professor of Medicine
InstitutionBrigham and Women's Hospital
AddressBrigham & Women's Hospital
HIM Bldg - Rm 641
77 Avenue Louis Pasteur
Boston MA 02115
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Available: 08/11/17, Expires: 06/01/19

Student will work with researchers using current techniques in molecular endocrinology to study thyroid hormone activation and inactivation and how this contributes to local changes in particular tissues and discrete times to mediate specific downstream effects.

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R01DK076117     (ZAVACKI, ANN M)Jul 1, 2006 - May 31, 2012
Role of Deiodinases in Thyroid Hormone Homeostasis
Role: Principal Investigator

K01DK065765     (ZAVACKI, ANN M)Sep 1, 2004 - Aug 31, 2007
Deiodinases in Thyroid Hormone Homeostasis
Role: Principal Investigator

F32DK009793     (ZAVACKI, ANN M)Sep 5, 1997
Role: Principal Investigator

R01DK044128     (ZAVACKI, ANN M)Jan 15, 1992 - May 31, 2019
Physiology of Thyroid Hormone-Dependent Gene Expression
Role: Co-Principal Investigator

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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.
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  1. Angell TE, Vyas CM, Medici M, Wang Z, Barletta JA, Benson CB, Cibas ES, Cho NL, Doherty GM, Doubilet PM, Frates MC, Gawande AA, Heller HT, Kim MI, Krane JF, Marqusee E, Moore FD, Nehs MA, Zavacki AM, Larsen PR, Alexander EK. Differential Growth Rates of Benign vs. Malignant Thyroid Nodules. J Clin Endocrinol Metab. 2017 Dec 01; 102(12):4642-4647. PMID: 29040691.
    View in: PubMed
  2. Akinrotimi O, Riessen R, VanDuyne P, Park JE, Lee YK, Wong LJ, Zavacki AM, Schoonjans K, Anakk S. Small heterodimer partner deletion prevents hepatic steatosis and when combined with farnesoid X receptor loss protects against type 2 diabetes in mice. Hepatology. 2017 12; 66(6):1854-1865. PMID: 28586124.
    View in: PubMed
  3. Wassner AJ, Jugo RH, Dorfman DM, Padera RF, Maynard MA, Zavacki AM, Jay PY, Huang SA. Myocardial Induction of Type 3 Deiodinase in Dilated Cardiomyopathy. Thyroid. 2017 05; 27(5):732-737. PMID: 28314380.
    View in: PubMed
  4. Luongo C, Martin C, Vella K, Marsili A, Ambrosio R, Dentice M, Harney JW, Salvatore D, Zavacki AM, Larsen PR. The selective loss of the type 2 iodothyronine deiodinase in mouse thyrotrophs increases basal TSH but blunts the thyrotropin response to hypothyroidism. Endocrinology. 2015 Feb; 156(2):745-54. PMID: 25456070; PMCID: PMC4298316.
  5. Bohinc BN, Michelotti G, Xie G, Pang H, Suzuki A, Guy CD, Piercy D, Kruger L, Swiderska-Syn M, Machado M, Pereira T, Zavacki AM, Abdelmalek M, Diehl AM. Repair-related activation of hedgehog signaling in stromal cells promotes intrahepatic hypothyroidism. Endocrinology. 2014 Nov; 155(11):4591-601. PMID: 25121996; PMCID: PMC4256825.
  6. Khan A, Harney JW, Zavacki AM, Sajdel-Sulkowska EM. Disrupted brain thyroid hormone homeostasis and altered thyroid hormone-dependent brain gene expression in autism spectrum disorders. J Physiol Pharmacol. 2014 Apr; 65(2):257-72. PMID: 24781735.
    View in: PubMed
  7. Salvatore D, Simonides WS, Dentice M, Zavacki AM, Larsen PR. Thyroid hormones and skeletal muscle--new insights and potential implications. Nat Rev Endocrinol. 2014 Apr; 10(4):206-14. PMID: 24322650; PMCID: PMC4037849.
  8. Xu M, Sulkowski ZL, Parekh P, Khan A, Chen T, Midha S, Iwasaki T, Shimokawa N, Koibuchi N, Zavacki AM, Sajdel-Sulkowska EM. Effects of perinatal lipopolysaccharide (LPS) exposure on the developing rat brain; modeling the effect of maternal infection on the developing human CNS. Cerebellum. 2013 Aug; 12(4):572-86. PMID: 23475384.
    View in: PubMed
  9. Zavacki AM, Larsen PR. RTHa, a newly recognized phenotype of the resistance to thyroid hormone (RTH) syndrome in patients with THRA gene mutations. J Clin Endocrinol Metab. 2013 Jul; 98(7):2684-6. PMID: 23837191; PMCID: PMC3701265.
  10. Aguayo-Mazzucato C, Zavacki AM, Marinelarena A, Hollister-Lock J, El Khattabi I, Marsili A, Weir GC, Sharma A, Larsen PR, Bonner-Weir S. Thyroid hormone promotes postnatal rat pancreatic ß-cell development and glucose-responsive insulin secretion through MAFA. Diabetes. 2013 May; 62(5):1569-80. PMID: 23305647; PMCID: PMC3636623.
  11. Kalló I, Mohácsik P, Vida B, Zeöld A, Bardóczi Z, Zavacki AM, Farkas E, Kádár A, Hrabovszky E, Arrojo E Drigo R, Dong L, Barna L, Palkovits M, Borsay BA, Herczeg L, Lechan RM, Bianco AC, Liposits Z, Fekete C, Gereben B. A novel pathway regulates thyroid hormone availability in rat and human hypothalamic neurosecretory neurons. PLoS One. 2012; 7(6):e37860. PMID: 22719854; PMCID: PMC3377717.
  12. Khan A, Sulkowski ZL, Chen T, Zavacki AM, Sajdel-Sulkowska EM. Sex-dependent changes in cerebellar thyroid hormone-dependent gene expression following perinatal exposure to thimerosal in rats. J Physiol Pharmacol. 2012 Jun; 63(3):277-83. PMID: 22791642.
    View in: PubMed
  13. Sulkowski ZL, Chen T, Midha S, Zavacki AM, Sajdel-Sulkowska EM. Maternal thimerosal exposure results in aberrant cerebellar oxidative stress, thyroid hormone metabolism, and motor behavior in rat pups; sex- and strain-dependent effects. Cerebellum. 2012 Jun; 11(2):575-86. PMID: 22015705.
    View in: PubMed
  14. Dentice M, Marsili A, Zavacki A, Larsen PR, Salvatore D. The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation. Biochim Biophys Acta. 2013 Jul; 1830(7):3937-45. PMID: 22634734; PMCID: PMC3670672.
  15. Zhu B, Shrivastava A, Luongo C, Chen T, Harney JW, Marsili A, Tran TV, Bhadouria A, Mopala R, Steen AI, Larsen PR, Zavacki AM. Catalysis leads to posttranslational inactivation of the type 1 deiodinase and alters its conformation. J Endocrinol. 2012 Jul; 214(1):87-94. PMID: 22544951; PMCID: PMC3612969.
  16. Larsen PR, Zavacki AM. The role of the iodothyronine deiodinases in the physiology and pathophysiology of thyroid hormone action. Eur Thyroid J. 2012; 1(4):232-242. PMID: 23750337.
    View in: PubMed
  17. Patwari P, Emilsson V, Schadt EE, Chutkow WA, Lee S, Marsili A, Zhang Y, Dobrin R, Cohen DE, Larsen PR, Zavacki AM, Fong LG, Young SG, Lee RT. The arrestin domain-containing 3 protein regulates body mass and energy expenditure. Cell Metab. 2011 Nov 02; 14(5):671-83. PMID: 21982743; PMCID: PMC3216113.
  18. Marsili A, Sanchez E, Singru P, Harney JW, Zavacki AM, Lechan RM, Larsen PR. Thyroxine-induced expression of pyroglutamyl peptidase II and inhibition of TSH release precedes suppression of TRH mRNA and requires type 2 deiodinase. J Endocrinol. 2011 Oct; 211(1):73-8. PMID: 21788297; PMCID: PMC3558748.
  19. Marsili A, Tang D, Harney JW, Singh P, Zavacki AM, Dentice M, Salvatore D, Larsen PR. Type II iodothyronine deiodinase provides intracellular 3,5,3'-triiodothyronine to normal and regenerating mouse skeletal muscle. Am J Physiol Endocrinol Metab. 2011 Nov; 301(5):E818-24. PMID: 21771965; PMCID: PMC3214000.
  20. Marsili A, Aguayo-Mazzucato C, Chen T, Kumar A, Chung M, Lunsford EP, Harney JW, Van-Tran T, Gianetti E, Ramadan W, Chou C, Bonner-Weir S, Larsen PR, Silva JE, Zavacki AM. Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity. PLoS One. 2011; 6(6):e20832. PMID: 21698184; PMCID: PMC3116839.
  21. Ramadan W, Marsili A, Larsen PR, Zavacki AM, Silva JE. Type-2 iodothyronine 5'deiodinase (D2) in skeletal muscle of C57Bl/6 mice. II. Evidence for a role of D2 in the hypermetabolism of thyroid hormone receptor alpha-deficient mice. Endocrinology. 2011 Aug; 152(8):3093-102. PMID: 21652727; PMCID: PMC3138235.
  22. Marsili A, Zavacki AM, Harney JW, Larsen PR. Physiological role and regulation of iodothyronine deiodinases: a 2011 update. J Endocrinol Invest. 2011 May; 34(5):395-407. PMID: 21427525; PMCID: PMC3687787.
  23. Marsili A, Ramadan W, Harney JW, Mulcahey M, Castroneves LA, Goemann IM, Wajner SM, Huang SA, Zavacki AM, Maia AL, Dentice M, Salvatore D, Silva JE, Larsen PR. Type 2 iodothyronine deiodinase levels are higher in slow-twitch than fast-twitch mouse skeletal muscle and are increased in hypothyroidism. Endocrinology. 2010 Dec; 151(12):5952-60. PMID: 20881246; PMCID: PMC2999482.
  24. Freitas BC, Gereben B, Castillo M, Kalló I, Zeöld A, Egri P, Liposits Z, Zavacki AM, Maciel RM, Jo S, Singru P, Sanchez E, Lechan RM, Bianco AC. Paracrine signaling by glial cell-derived triiodothyronine activates neuronal gene expression in the rodent brain and human cells. J Clin Invest. 2010 Jun; 120(6):2206-17. PMID: 20458138; PMCID: PMC2877954.
  25. Christoffolete MA, Doleschall M, Egri P, Liposits Z, Zavacki AM, Bianco AC, Gereben B. Regulation of thyroid hormone activation via the liver X-receptor/retinoid X-receptor pathway. J Endocrinol. 2010 May; 205(2):179-86. PMID: 20176747; PMCID: PMC3133926.
  26. Simmen FA, Mercado CP, Zavacki AM, Huang SA, Greenway AD, Kang P, Bowman MT, Prior RL. Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat. J Nutr Biochem. 2010 Nov; 21(11):1106-13. PMID: 19962299.
    View in: PubMed
  27. Aerts G, Arrojo E Drigo R, Van Herck SL, Sammels E, Mirebeau-Prunier D, Gereben B, Zeöld A, Harney JW, Huang SA, Mulcahey MA, Van der Geyten S, Van den Bergh G, Arckens L, Darras VM, Zavacki AM. Knockdown of the type 3 iodothyronine deiodinase (D3) interacting protein peroxiredoxin 3 decreases D3-mediated deiodination in intact cells. Endocrinology. 2009 Nov; 150(11):5171-80. PMID: 19819956; PMCID: PMC2775988.
  28. Zavacki AM, Arrojo E Drigo R, Freitas BC, Chung M, Harney JW, Egri P, Wittmann G, Fekete C, Gereben B, Bianco AC. The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase. Mol Cell Biol. 2009 Oct; 29(19):5339-47. PMID: 19651899; PMCID: PMC2747977.
  29. Isganaitis E, Jimenez-Chillaron J, Woo M, Chow A, DeCoste J, Vokes M, Liu M, Kasif S, Zavacki AM, Leshan RL, Myers MG, Patti ME. Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice. Diabetes. 2009 May; 58(5):1192-200. PMID: 19208909; PMCID: PMC2671035.
  30. Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeöld A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008 Dec; 29(7):898-938. PMID: 18815314; PMCID: PMC2647704.
  31. Sánchez E, Singru PS, Acharya R, Bodria M, Fekete C, Zavacki AM, Bianco AC, Lechan RM. Differential effects of refeeding on melanocortin-responsive neurons in the hypothalamic paraventricular nucleus. Endocrinology. 2008 Sep; 149(9):4329-35. PMID: 18467436; PMCID: PMC2553369.
  32. Dentice M, Luongo C, Huang S, Ambrosio R, Elefante A, Mirebeau-Prunier D, Zavacki AM, Fenzi G, Grachtchouk M, Hutchin M, Dlugosz AA, Bianco AC, Missero C, Larsen PR, Salvatore D. Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes. Proc Natl Acad Sci U S A. 2007 Sep 04; 104(36):14466-71. PMID: 17720805; PMCID: PMC1964817.
  33. Sagar GD, Gereben B, Callebaut I, Mornon JP, Zeöld A, da Silva WS, Luongo C, Dentice M, Tente SM, Freitas BC, Harney JW, Zavacki AM, Bianco AC. Ubiquitination-induced conformational change within the deiodinase dimer is a switch regulating enzyme activity. Mol Cell Biol. 2007 Jul; 27(13):4774-83. PMID: 17452445; PMCID: PMC1951476.
  34. Christoffolete MA, Arrojo e Drigo R, Gazoni F, Tente SM, Goncalves V, Amorim BS, Larsen PR, Bianco AC, Zavacki AM. Mice with impaired extrathyroidal thyroxine to 3,5,3'-triiodothyronine conversion maintain normal serum 3,5,3'-triiodothyronine concentrations. Endocrinology. 2007 Mar; 148(3):954-60. PMID: 17138654.
    View in: PubMed
  35. Dentice M, Bandyopadhyay A, Gereben B, Callebaut I, Christoffolete MA, Kim BW, Nissim S, Mornon JP, Zavacki AM, Zeöld A, Capelo LP, Curcio-Morelli C, Ribeiro R, Harney JW, Tabin CJ, Bianco AC. The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate. Nat Cell Biol. 2005 Jul; 7(7):698-705. PMID: 15965468; PMCID: PMC1761694.
  36. Kalaany NY, Gauthier KC, Zavacki AM, Mammen PP, Kitazume T, Peterson JA, Horton JD, Garry DJ, Bianco AC, Mangelsdorf DJ. LXRs regulate the balance between fat storage and oxidation. Cell Metab. 2005 Apr; 1(4):231-44. PMID: 16054068.
    View in: PubMed
  37. Zavacki AM, Larsen PR. CARs and drugs: a risky combination. Endocrinology. 2005 Mar; 146(3):992-4. PMID: 15713940.
    View in: PubMed
  38. Zavacki AM, Ying H, Christoffolete MA, Aerts G, So E, Harney JW, Cheng SY, Larsen PR, Bianco AC. Type 1 iodothyronine deiodinase is a sensitive marker of peripheral thyroid status in the mouse. Endocrinology. 2005 Mar; 146(3):1568-75. PMID: 15591136.
    View in: PubMed
  39. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jäger S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman GI, Lowell BB, Krainc D, Spiegelman BM. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell. 2004 Oct 01; 119(1):121-35. PMID: 15454086.
    View in: PubMed
  40. Morozova N, Forry EP, Shahid E, Zavacki AM, Harney JW, Kraytsberg Y, Berry MJ. Antioxidant function of a novel selenoprotein in Drosophila melanogaster. Genes Cells. 2003 Dec; 8(12):963-71. PMID: 14750951.
    View in: PubMed
  41. Kim BW, Zavacki AM, Curcio-Morelli C, Dentice M, Harney JW, Larsen PR, Bianco AC. Endoplasmic reticulum-associated degradation of the human type 2 iodothyronine deiodinase (D2) is mediated via an association between mammalian UBC7 and the carboxyl region of D2. Mol Endocrinol. 2003 Dec; 17(12):2603-12. PMID: 12933904.
    View in: PubMed
  42. Curcio-Morelli C, Zavacki AM, Christofollete M, Gereben B, de Freitas BC, Harney JW, Li Z, Wu G, Bianco AC. Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation. J Clin Invest. 2003 Jul; 112(2):189-96. PMID: 12865408; PMCID: PMC164294.
  43. Zavacki AM, Mansell JB, Chung M, Klimovitsky B, Harney JW, Berry MJ. Coupled tRNA(Sec)-dependent assembly of the selenocysteine decoding apparatus. Mol Cell. 2003 Mar; 11(3):773-81. PMID: 12667458.
    View in: PubMed
  44. Curcio-Morelli C, Gereben B, Zavacki AM, Kim BW, Huang S, Harney JW, Larsen PR, Bianco AC. In vivo dimerization of types 1, 2, and 3 iodothyronine selenodeiodinases. Endocrinology. 2003 Mar; 144(3):937-46. PMID: 12586771.
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  45. Seo YW, Sanyal S, Kim HJ, Won DH, An JY, Amano T, Zavacki AM, Kwon HB, Shi YB, Kim WS, Kang H, Moore DD, Choi HS. FOR, a novel orphan nuclear receptor related to farnesoid X receptor. J Biol Chem. 2002 May 17; 277(20):17836-44. PMID: 11867625.
    View in: PubMed
  46. Laffitte BA, Kast HR, Nguyen CM, Zavacki AM, Moore DD, Edwards PA. Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J Biol Chem. 2000 Apr 07; 275(14):10638-47. PMID: 10744760.
    View in: PubMed
  47. Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD, Lehmann JM. Bile acids: natural ligands for an orphan nuclear receptor. Science. 1999 May 21; 284(5418):1365-8. PMID: 10334993.
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  48. Lee YK, Tzameli I, Zavacki AM, Moore DD. Recent progress in orphan nuclear hormone receptors. Journal of Biochemistry and Molecular Biology. 1998; 31(5):419-26.
  49. Zavacki AM, Lehmann JM, Seol W, Willson TM, Kliewer SA, Moore DD. Activation of the orphan receptor RIP14 by retinoids. Proc Natl Acad Sci U S A. 1997 Jul 22; 94(15):7909-14. PMID: 9223286; PMCID: PMC21528.
  50. Zavacki AM, Harney JW, Brent GA, Larsen PR. Structural features of thyroid hormone response elements that increase susceptibility to inhibition by an RTH mutant thyroid hormone receptor. Endocrinology. 1996 Jul; 137(7):2833-41. PMID: 8770904.
    View in: PubMed
  51. Zavacki AM, Zhang CY, Harney JW, Larsen PR. Enhancement of thyroid hormone receptor isoform specificity by insertion of a distant half-site into a thyroid hormone response element. Endocrinology. 1996 Apr; 137(4):1438-46. PMID: 8625922.
    View in: PubMed
  52. Ann Marie Zavacki. Defining Mechanisms of Thyroid Hormone Action. 1996.
  53. Toyoda N, Zavacki AM, Maia AL, Harney JW, Larsen PR. A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene. Mol Cell Biol. 1995 Sep; 15(9):5100-12. PMID: 7651427; PMCID: PMC230757.
  54. Hsu JH, Zavacki AM, Harney JW, Brent GA. Retinoid-X receptor (RXR) differentially augments thyroid hormone response in cell lines as a function of the response element and endogenous RXR content. Endocrinology. 1995 Feb; 136(2):421-30. PMID: 7835272.
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  55. Williams GR, Zavacki AM, Harney JW, Brent GA. Thyroid hormone receptor binds with unique properties to response elements that contain hexamer domains in an inverted palindrome arrangement. Endocrinology. 1994 Apr; 134(4):1888-96. PMID: 8137757.
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  56. Zavacki AM, Harney JW, Brent GA, Larsen PR. Dominant negative inhibition by mutant thyroid hormone receptors is thyroid hormone response element and receptor isoform specific. Mol Endocrinol. 1993 Oct; 7(10):1319-30. PMID: 8264663.
    View in: PubMed
  57. Arvan P, Kuliawat R, Prabakaran D, Zavacki AM, Elahi D, Wang S, Pilkey D. Protein discharge from immature secretory granules displays both regulated and constitutive characteristics. J Biol Chem. 1991 Aug 05; 266(22):14171-4. PMID: 1860833.
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  58. Hinkle PM, Jackson AE, Thompson TM, Zavacki AM, Coppola DA, Bancroft C. Calcium channel agonists and antagonists: effects of chronic treatment on pituitary prolactin synthesis and intracellular calcium. Mol Endocrinol. 1988 Nov; 2(11):1132-8. PMID: 3221879.
    View in: PubMed
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