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    Jack L Leonard PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentMicrobiology and Physiological Systems
    AddressUniversity of Massachusetts Medical School
    55 Lake Avenue North
    Worcester MA 01655
    Phone508-856-6687
      Other Positions
      InstitutionUMMS - School of Medicine
      DepartmentAnesthesiology

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Academic Background

        B.A., California State University-Fresno;
        Ph.D., University of California-Berkeley, 1976.

        Cellular and Molecular Events that Mediate Thyroid Hormone Action in the Brain

        Jack Leonard

        The focus of this laboratory is the characterization of cellular and molecular events that mediate thyroidhormone action in the brain. Current studies include: cloning and sequencing of the plasma membrane-bound enzyme that bioactivates thyroid hormone; determination of the subunit structure and physiochemical properties of the enzyme polypeptide; characterization of the internalization, sorting and degradation pathway(s) of short-lived membrane proteins in the brain; sequencing of a 55 kDa actin-binding protein whose interactions with actin are hormonally regulated; characterization of the isotypes of erb-a gene products present in cultured cerebrocortical astrocytes; identification of cyclic nucleotide-induced gene products in cultured glial cells using substraction cloning; and determination of the developmental programming of cytoskeletal and integrin gene products in cultured fetal brain cells.

        See our research movie.

        neuron

        This is a GFP expressing neuron.



        Rotation Projects

        Potential Rotation Projects

        1. Real-time imaging of synaptic vesicle recycling will be done using cultured cerebellar granule neurons, dynamic confocal microscopy, vesicle specific fluorescent dyes, a cohort of GFP-tagged SV marker proteins. The student will learn contemporary techniques in cell and molecular neurobiology.


        2. In vitro propagated cerebellar progenitor cells isolated from a family of thyroid hormone receptor mutants will be implanted into normal neonatal mice and the developmental fate of the implanted cells characterized. The student will learn immunocytochemistry, FACS analysis, and transcript profiling using Affymetrix chip technology.


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Cheng SY, Leonard JL, Davis PJ. Molecular aspects of thyroid hormone actions. Endocr Rev. 2010 Apr; 31(2):139-70.
          View in: PubMed
        2. Farwell AP, Leonard JL. Effect of methyl iodide on deiodinase activity. Inhal Toxicol. 2009 May; 21(6):497-504.
          View in: PubMed
        3. Leonard JL. Non-genomic actions of thyroid hormone in brain development. Steroids. 2008 Oct; 73(9-10):1008-12.
          View in: PubMed
        4. Davis PJ, Leonard JL, Davis FB. Mechanisms of nongenomic actions of thyroid hormone. Front Neuroendocrinol. 2008 May; 29(2):211-8.
          View in: PubMed
        5. Simpson GI, Leonard DM, Leonard JL. Identification of the key residues responsible for the assembly of selenodeiodinases. J Biol Chem. 2006 May 26; 281(21):14615-21.
          View in: PubMed
        6. Farwell AP, Dubord-Tomasetti SA, Pietrzykowski AZ, Leonard JL. Dynamic nongenomic actions of thyroid hormone in the developing rat brain. Endocrinology. 2006 May; 147(5):2567-74.
          View in: PubMed
        7. Alkemade A, Friesema EC, Unmehopa UA, Fabriek BO, Kuiper GG, Leonard JL, Wiersinga WM, Swaab DF, Visser TJ, Fliers E. Neuroanatomical pathways for thyroid hormone feedback in the human hypothalamus. J Clin Endocrinol Metab. 2005 Jul; 90(7):4322-34.
          View in: PubMed
        8. Leonard JL, Simpson G, Leonard DM. Characterization of the protein dimerization domain responsible for assembly of functional selenodeiodinases. J Biol Chem. 2005 Mar 25; 280(12):11093-100.
          View in: PubMed
        9. Farwell AP, Dubord-Tomasetti SA, Pietrzykowski AZ, Stachelek SJ, Leonard JL. Regulation of cerebellar neuronal migration and neurite outgrowth by thyroxine and 3,3',5'-triiodothyronine. Brain Res Dev Brain Res. 2005 Jan 1; 154(1):121-35.
          View in: PubMed
        10. Dobson JG, Fray J, Leonard JL, Pratt RE. Molecular mechanisms of reduced beta-adrenergic signaling in the aged heart as revealed by genomic profiling. Physiol Genomics. 2003 Oct 17; 15(2):142-7.
          View in: PubMed
        11. Diano S, Leonard JL, Meli R, Esposito E, Schiavo L. Hypothalamic type II iodothyronine deiodinase: a light and electron microscopic study. Brain Res. 2003 Jun 20; 976(1):130-4.
          View in: PubMed
        12. Verhoelst CH, Vandenborne K, Severi T, Bakker O, Zandieh Doulabi B, Leonard JL, Kühn ER, van der Geyten S, Darras VM. Specific detection of type III iodothyronine deiodinase protein in chicken cerebellar purkinje cells. Endocrinology. 2002 Jul; 143(7):2700-7.
          View in: PubMed
        13. Stachelek SJ, Tuft RA, Lifschitz LM, Leonard DM, Farwell AP, Leonard JL. Real-time visualization of processive myosin 5a-mediated vesicle movement in living astrocytes. J Biol Chem. 2001 Sep 21; 276(38):35652-9.
          View in: PubMed
        14. Vacanti MP, Leonard JL, Dore B, Bonassar LJ, Cao Y, Stachelek SJ, Vacanti JP, O'Connell F, Yu CS, Farwell AP, Vacanti CA. Tissue-engineered spinal cord. Transplant Proc. 2001 Feb-Mar; 33(1-2):592-8.
          View in: PubMed
        15. Leonard JL, Visser TJ, Leonard DM. Characterization of the subunit structure of the catalytically active type I iodothyronine deiodinase. J Biol Chem. 2001 Jan 26; 276(4):2600-7.
          View in: PubMed
        16. Stachelek SJ, Kowalik TF, Farwell AP, Leonard JL. Myosin V plays an essential role in the thyroid hormone-dependent endocytosis of type II iodothyronine 5'-deiodinase. J Biol Chem. 2000 Oct 13; 275(41):31701-7.
          View in: PubMed
        17. Leonard DM, Stachelek SJ, Safran M, Farwell AP, Kowalik TF, Leonard JL. Cloning, expression, and functional characterization of the substrate binding subunit of rat type II iodothyronine 5'-deiodinase. J Biol Chem. 2000 Aug 18; 275(33):25194-201.
          View in: PubMed
        18. Dowling AL, Martz GU, Leonard JL, Zoeller RT. Acute changes in maternal thyroid hormone induce rapid and transient changes in gene expression in fetal rat brain. J Neurosci. 2000 Mar 15; 20(6):2255-65.
          View in: PubMed
        19. Sanders JP, Van der Geyten S, Kaptein E, Darras VM, Kühn ER, Leonard JL, Visser TJ. Cloning and characterization of type III iodothyronine deiodinase from the fish Oreochromis niloticus. Endocrinology. 1999 Aug; 140(8):3666-73.
          View in: PubMed
        20. Leonard JL, Leonard DM, Safran M, Wu R, Zapp ML, Farwell AP. The mammalian homolog of the frog type II selenodeiodinase does not encode a functional enzyme in the rat. Endocrinology. 1999 May; 140(5):2206-15.
          View in: PubMed
        21. Shen Q, Wu R, Leonard JL, Newburger PE. Identification and molecular cloning of a human selenocysteine insertion sequence-binding protein. A bifunctional role for DNA-binding protein B. J Biol Chem. 1998 Mar 6; 273(10):5443-6.
          View in: PubMed
        22. Van der Geyten S, Sanders JP, Kaptein E, Darras VM, Kühn ER, Leonard JL, Visser TJ. Expression of chicken hepatic type I and type III iodothyronine deiodinases during embryonic development. Endocrinology. 1997 Dec; 138(12):5144-52.
          View in: PubMed
        23. Sanders JP, Van der Geyten S, Kaptein E, Darras VM, Kühn ER, Leonard JL, Visser TJ. Characterization of a propylthiouracil-insensitive type I iodothyronine deiodinase. Endocrinology. 1997 Dec; 138(12):5153-60.
          View in: PubMed
        24. Leonard JL, Farwell AP. Thyroid hormone-regulated actin polymerization in brain. Thyroid. 1997 Feb; 7(1):147-51.
          View in: PubMed
        25. Safran M, Farwell AP, Leonard JL. Catalytic activity of type II iodothyronine 5'-deiodinase polypeptide is dependent upon a cyclic AMP activation factor. J Biol Chem. 1996 Jul 5; 271(27):16363-8.
          View in: PubMed
        26. Farwell AP, Safran M, Dubord S, Leonard JL. Degradation and recycling of the substrate-binding subunit of type II iodothyronine 5'-deiodinase in astrocytes. J Biol Chem. 1996 Jul 5; 271(27):16369-74.
          View in: PubMed
        27. Leonard JL, Leonard DM, Shen Q, Farwell AP, Newburger PE. Selenium-regulated translation control of heterologous gene expression: normal function of selenocysteine-substituted gene products. J Cell Biochem. 1996 Jun 1; 61(3):410-9.
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        28. Farwell AP, Tranter MP, Leonard JL. Thyroxine-dependent regulation of integrin-laminin interactions in astrocytes. Endocrinology. 1995 Sep; 136(9):3909-15.
          View in: PubMed
        29. Shen Q, Leonard JL, Newburger PE. Structure and function of the selenium translation element in the 3'-untranslated region of human cellular glutathione peroxidase mRNA. RNA. 1995 Jul; 1(5):519-25.
          View in: PubMed
        30. Leonard JL, Farwell AP, Yen PM, Chin WW, Stula M. Differential expression of thyroid hormone receptor isoforms in neurons and astroglial cells. Endocrinology. 1994 Aug; 135(2):548-55.
          View in: PubMed
        31. Chanoine JP, Veronikis I, Alex S, Stone S, Fang SL, Leonard JL, Braverman LE. The postnatal serum 3,5,3'-triiodothyronine (T3) surge in the rat is largely independent of extrathyroidal 5'-deiodination of thyroxine to T3. Endocrinology. 1993 Dec; 133(6):2604-9.
          View in: PubMed
        32. Chanoine JP, Alex S, Stone S, Fang SL, Veronikis I, Leonard JL, Braverman LE. Placental 5-deiodinase activity and fetal thyroid hormone economy are unaffected by selenium deficiency in the rat. Pediatr Res. 1993 Sep; 34(3):288-92.
          View in: PubMed
        33. Safran M, Farwell AP, Rokos H, Leonard JL. Structural requirements of iodothyronines for the rapid inactivation and internalization of type II iodothyronine 5'-deiodinase in glial cells. J Biol Chem. 1993 Jul 5; 268(19):14224-9.
          View in: PubMed
        34. Chanoine JP, Braverman LE, Farwell AP, Safran M, Alex S, Dubord S, Leonard JL. The thyroid gland is a major source of circulating T3 in the rat. J Clin Invest. 1993 Jun; 91(6):2709-13.
          View in: PubMed
        35. Farwell AP, DiBenedetto DJ, Leonard JL. Thyroxine targets different pathways of internalization of type II iodothyronine 5'-deiodinase in astrocytes. J Biol Chem. 1993 Mar 5; 268(7):5055-62.
          View in: PubMed
        36. Safran M, Farwell AP, Leonard JL. Thyroid hormone-dependent redistribution of the 55-kilodalton monomer of protein disulfide isomerase in cultured glial cells. Endocrinology. 1992 Nov; 131(5):2413-8.
          View in: PubMed
        37. Chanoine JP, Safran M, Farwell AP, Dubord S, Alex S, Stone S, Arthur JR, Braverman LE, Leonard JL. Effects of selenium deficiency on thyroid hormone economy in rats. Endocrinology. 1992 Oct; 131(4):1787-92.
          View in: PubMed
        38. Farwell AP, Leonard JL. Dissociation of actin polymerization and enzyme inactivation in the hormonal regulation of type II iodothyronine 5'-deiodinase activity in astrocytes. Endocrinology. 1992 Aug; 131(2):721-8.
          View in: PubMed
        39. Chanoine JP, Alex S, Fang SL, Stone S, Leonard JL, Körhle J, Braverman LE. Role of transthyretin in the transport of thyroxine from the blood to the choroid plexus, the cerebrospinal fluid, and the brain. Endocrinology. 1992 Feb; 130(2):933-8.
          View in: PubMed
        40. Safran M, Leonard JL. Characterization of a N-bromoacetyl-L-thyroxine affinity-labeled 55-kilodalton protein as protein disulfide isomerase in cultured glial cells. Endocrinology. 1991 Oct; 129(4):2011-6.
          View in: PubMed
        41. Safran M, Farwell AP, Leonard JL. Evidence that type II 5'-deiodinase is not a selenoprotein. J Biol Chem. 1991 Jul 25; 266(21):13477-80.
          View in: PubMed
        42. Leonard JL, Ekenbarger DM, Frank SJ, Farwell AP, Koehrle J. Localization of type I iodothyronine 5'-deiodinase to the basolateral plasma membrane in renal cortical epithelial cells. J Biol Chem. 1991 Jun 15; 266(17):11262-9.
          View in: PubMed
        43. Safran M, Leonard JL. Comparison of the physicochemical properties of type I and type II iodothyronine 5'-deiodinase. J Biol Chem. 1991 Feb 15; 266(5):3233-8.
          View in: PubMed
        44. Farwell AP, Lynch RM, Okulicz WC, Comi AM, Leonard JL. The actin cytoskeleton mediates the hormonally regulated translocation of type II iodothyronine 5'-deiodinase in astrocytes. J Biol Chem. 1990 Oct 25; 265(30):18546-53.
          View in: PubMed
        45. Frick GP, Leonard JL, Goodman HM. Effect of hypophysectomy on growth hormone receptor gene expression in rat tissues. Endocrinology. 1990 Jun; 126(6):3076-82.
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        46. Köhrle J, Rasmussen UB, Rokos H, Leonard JL, Hesch RD. Selective affinity labeling of a 27-kDa integral membrane protein in rat liver and kidney with N-bromoacetyl derivatives of L-thyroxine and 3,5,3'-triiodo-L-thyronine. J Biol Chem. 1990 Apr 15; 265(11):6146-54.
          View in: PubMed
        47. Köhrle J, Rasmussen UB, Ekenbarger DM, Alex S, Rokos H, Hesch RD, Leonard JL. Affinity labeling of rat liver and kidney type I 5'-deiodinase. Identification of the 27-kDa substrate binding subunit. J Biol Chem. 1990 Apr 15; 265(11):6155-63.
          View in: PubMed
        48. Siegrist-Kaiser CA, Juge-Aubry C, Tranter MP, Ekenbarger DM, Leonard JL. Thyroxine-dependent modulation of actin polymerization in cultured astrocytes. A novel, extranuclear action of thyroid hormone. J Biol Chem. 1990 Mar 25; 265(9):5296-302.
          View in: PubMed
        49. Safran M, Köhrle J, Braverman LE, Leonard JL. Effect of biological alterations of type I 5'deiodinase activity on affinity labeled membrane proteins in rat liver and kidney. Endocrinology. 1990 Feb; 126(2):826-31.
          View in: PubMed
        50. Leonard JL, Siegrist-Kaiser CA, Zuckerman CJ. Regulation of type II iodothyronine 5'-deiodinase by thyroid hormone. Inhibition of actin polymerization blocks enzyme inactivation in cAMP-stimulated glial cells. J Biol Chem. 1990 Jan 15; 265(2):940-6.
          View in: PubMed
        51. Farwell AP, Leonard JL. Identification of a 27-kDa protein with the properties of type II iodothyronine 5'-deiodinase in dibutyryl cyclic AMP-stimulated glial cells. J Biol Chem. 1989 Dec 5; 264(34):20561-7.
          View in: PubMed
        52. Leonard JL. Dibutyryl cAMP induction of type II 5'deiodinase activity in rat brain astrocytes in culture. Biochem Biophys Res Commun. 1988 Mar 30; 151(3):1164-72.
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        53. Kolodny JM, Leonard JL, Larsen PR, Silva JE. Studies of nuclear 3,5,3'-triiodothyronine binding in primary cultures of rat brain. Endocrinology. 1985 Nov; 117(5):1848-57.
          View in: PubMed
        54. Watson AY, Leonard JL, Radie KA, Mellen SA, Murphy RA. Alterations in the pituitary-thyroid axis and 5'-deiodinase activity in mice with muscular dystrophy. Endocrinology. 1985 Jun; 116(6):2201-8.
          View in: PubMed
        55. Silva JE, Leonard JL. Regulation of rat cerebrocortical and adenohypophyseal type II 5'-deiodinase by thyroxine, triiodothyronine, and reverse triiodothyronine. Endocrinology. 1985 Apr; 116(4):1627-35.
          View in: PubMed
        56. Leonard JL, Larsen PR. Thyroid hormone metabolism in primary cultures of fetal rat brain cells. Brain Res. 1985 Feb 18; 327(1-2):1-13.
          View in: PubMed
        57. Koenig RJ, Leonard JL, Senator D, Rappaport N, Watson AY, Larsen PR. Regulation of thyroxine 5'-deiodinase activity by 3,5,3'-triiodothyronine in cultured rat anterior pituitary cells. Endocrinology. 1984 Jul; 115(1):324-9.
          View in: PubMed
        58. Leonard JL, Silva JE, Kaplan MM, Mellen SA, Visser TJ, Larsen PR. Acute posttranscriptional regulation of cerebrocortical and pituitary iodothyronine 5'-deiodinases by thyroid hormone. Endocrinology. 1984 Mar; 114(3):998-1004.
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        59. Silva JE, Leonard JL, Crantz FR, Larsen PR. Evidence for two tissue-specific pathways for in vivo thyroxine 5'-deiodination in the rat. J Clin Invest. 1982 May; 69(5):1176-84.
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        60. Kaplan MM, McCann UD, Yaskoski KA, Larsen PR, Leonard JL. Anatomical distribution of phenolic and tyrosyl ring iodothyronine deiodinases in the nervous system of normal and hypothyroid rats. Endocrinology. 1981 Aug; 109(2):397-402.
          View in: PubMed
        61. Leonard JL, Rosenberg IN. Iodothyronine 5'-deiodinase from rat kidney: substrate specificity and the 5'-deiodination of reverse triiodothyronine. Endocrinology. 1980 Nov; 107(5):1376-83.
          View in: PubMed
        62. Leonard JL, Rosenberg IN. Characterization of essential enzyme sulfhydryl groups of thyroxine 5'-deiodinase from rat kidney. Endocrinology. 1980 Feb; 106(2):444-51.
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        63. Leonard JL, Rosenberg IN. Thyroxine 5'-deiodinase activity of rat kidney: observations on activation by thiols and inhibition by propylthiouracil. Endocrinology. 1978 Dec; 103(6):2137-44.
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