Our laboratory focuses on understanding the consequences of alterations in thyroid hormone exposure during different developmental periods for the hypothalamic-pituitary-thyroid axis, endocrine function, and neurological and behavioral outcomes. Abnormal levels of thyroid hormones are rather prevalent in humans due to disease of the thyroid gland, and can also occur during pregnancy, influencing fetal development.
We utilize mouse models with deficiency in the type 3 deiodinase gene (Dio3) and other transgenic mouse strains. Dio3 is as a key determinant of thyroid hormone exposure in both developing and adult tissues, as it encodes a selenoenzymethat converts thyroid hormones into metabolites that are biologically inactive, thus limiting thyroid hormone action in the tissues in which it is expressed and contributing to the clearance of thyroid hormones from the circulation. Using these models, we study endpoints that are relevant to a number of endocrineconditions including, obesity, type 2 diabetes and infertility, and to certain neurodevelopmental disorders such as autism, schizophrenia and depression.
Dio3 isalso an imprinted gene and, as such, it is regulated by epigenetic mechanisms that determine its allelic expression ratio and adequate gene dosage in a tissue- and developmental-specific manner. Thus, a second focus of our research is to understand such mechanisms, how they can be influenced by environmental factors, and to determine the situations in which altered epigenetic programming of Dio3 expression can lead to abnormal exposure to thyroid hormone, and to endocrine and neurological disease.
Selected Original Research from the Lab in Recent Years
Martinez ME, Duarte CW, Stohn JP, Karaczyn A, Wu Z, DeMambro VE and Hernandez A (2018). Thyroid Hormone Influences Brain Gene Expression Programs and Behaviors in Later Generations by Altering Germ Line Epigenetic Information. Mol. Psychiatry, in press.
Stohn JP, Martinez ME, Zafer M, Lopez-Espindola, D, Keyes LM, Hernandez A (2018). Increased Aggression and Lack of Maternal Behavior in DIO3-Deficient Mice are Associated with Abnormalities in Oxytocin and Vasopressin Systems. Genes, Brain and Behavior 17(1): 23-35.
Wu Z, Martinez ME, St. Germain DL and Hernandez A (2017). Type 3 Deiodinase Role on Central Thyroid Hormone Action Affects the Leptin-Melanocortin System and Circadian Activity. Endocrinology, 158: 419-430.
Stohn JP, Martinez ME and Hernandez A (2016). Decreased Anxiety- and Depression-like Behaviors and Hyperactivity in a Type 3 Deiodinase-Deficient Mouse Showing Brain Thyrotoxicosis and Peripheral Hypothyroidism. Psychoneuroendocrinology, 74: 46-56
Stohn JP, Martinez ME, Matoin K, Morte B, Bernal J, Galton VA, St. Germain DL, Hernandez A (2016). MCT8 Deficiency in Male Mice Mitigates the Phenotypic Abnormalities Associated with the Absence of a Functional Type 3 Deiodinase. Endocrinology, 157(8): 3266-3277.
Martinez ME, Cox DF, Youth BP, Hernandez A (2016). Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14. Eur J Human Genetics, 24: 1617-1621.
Martinez ME, Karaczyn A, Stohn JP, Donnelly WT, Croteau W, Peeters RP, Galton VA, Forrest D, St. Germain DL and Hernandez A (2016). The Type 3 Deiodinase is a Critical Determinant of Appropriate Thyroid Hormone Action in the Developing Testis . Endocrinology, 157(3): 1276-1288.
Martinez ME, Charalambous M, Saferali A, Fiering SN, Naoumova A, St. Germain DL, Ferguson-Smith AC and Hernandez A (2014). Genomic Imprinting Variations in the Mouse Type 3 Deiodinase Gene Between Tissues and Brain Regions. Mol Endocrinology, 28 (11): 1875-1886.
- Member, Graduate Faculty, Graduate School of Biomedical Sciences and Engineering, University of Maine
- Faculty Scientist II, Department of Molecular Medicine, Maine Medical Center Research Institute
- Ad hoc member of the Molecular and Cellular Endocrinology NIH Study Section on October 2012, October 2014, February 2015, October 2015.
- Editorial Board Member and active reviewer: Endocrinology (2013-present)
- Editorial Board Member and active reviewer: Molecular Endocrinology (2012-present)
- Ad hoc reviewer -Thyroid
- Ad hoc reviewer – Biological Psychiatry
- Ad hoc reviewer -Epigenetics
- Ad hoc reviewer – NeuroToxicology
- Ad hoc reviewer – Journal of Clinical Endocrinology and Metabolism
- Ad hoc reviewer – International Immunopharmacology
- Member, Endocrine Society (2003-present)
- Instructor, Endocrine Journal Club, Graduate School of Biomedical Sciences, University of Maine
- Lecturer, Cell Biology of Tissue Development and Function, Graduate School of Biomedical Sciences, University of Maine
- Co-Instructor, Endocrine Physiology, Medical School Program for 1st year Students, Geisel School of Medicine at Dartmouth
- Co-Instructor, Environmental Influences on the Reproductive axis, Graduate Program in Experimental and Molecular Medicine, Geisel School of Medicine at Dartmouth
- Co-Instructor, Ethics in Research, Undergraduate Program of Dartmouth College