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
Hernandez A (2021). Towards Epigenetic Profiling of Thyroid Hormone Status. J. Clin. Endo. Metab. in press, dgab141, https://doi.org/10.1210/clinem/dgab141
Galton VA, Martinez ME, Dragon JA, St Germain DL and Hernandez A (2021). The Intrinsic Activity of Thyroxine is Critical for Survival and Growth and Regulates Gene expression in Neonatal Liver. Thyroid, 31(3): 528-541.
Martinez ME, Duarte CW, Stohn JP, Karaczyn A, Wu Z, DeMambro VE and Hernandez A (2020). Thyroid Hormone Influences Brain Gene Expression Programs and Behaviors in Later Generations by Altering Germ Line Epigenetic Information. Mol. Psychiatry 25: 939-950.
Stohn JP, Martinez ME, St. Germain DL and Hernandez A (2019). Adult Onset of Type 3 Deiodinase Deficiency Increases Locomotor Activity and Alters Brain Gene Expression. Psychoneuroendocrinology, in press. (https://doi.org/10.1016/j.psyneuen.2019.104439)
Martinez ME, Duarte CW, Karaczyn A, Griswold M and Hernandez A (2019). Spermatogonial Type 3 Deiodinase Regulates Thyroid Hormone Action in Developing Testicular Somatic Cells. Endocrinology, 160(12): 2929-2945.
Hernandez A (2019). Cognitive function in hypothyroidism: What is that deiodinase again? J Clin Invest, 129 (1): 55-57.
Hernandez A (2019). Thyroid Hormone and Alcoholic fatty Liver: The Developmental Input. Alcoholism: Clin and Exp Res 43(9):1834-8137.
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.
Hernandez A (2015). 3,5-Diiodo-L-Thyronine in Dietary Supplements: What are the physiological Effects? Endocrinology 156(1): 5-7.
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.
- Faculty Scientist III, Center for Molecular Medicine, MaineHealth Institute for Research, MaineHealth
- Member, Graduate Faculty, Graduate School of Biomedical Sciences and Engineering, University of Maine
- Associate Professor of Medicine, Tufts University School of Medicine
- Member, American Thyroid Association
- Member, The Endocrine Society
- Member, Society for Neuroscience
- Member, International Behavioral and Neural Genetics Society
- Chartered Member, NIH Molecular and Cellular Endocrinology Study Section (2016-2020)
- Ad hoc member Molecular and Cellular Endocrinology Study Section and of the Basic Mechanisms of Diabetes and Metabolism Study Section at NIH
- Editorial Board Member Endocrinology (2013-2017)
- Editorial Board Member Molecular Endocrinology (2012-2017)
- Ad hoc reviewer for 30+ journals in the areas of genetics, endocrinology, neuroscience, development and medicine
February 2006 – Ethics in Research for Undergraduate Students, Dartmouth Medical School
Spring 2008 – Environmental Influences on the Reproductive Axis: a postgraduate course; part of the Ph.D. Program in Experimental and Molecular Medicine, Dartmouth Medical School, Hanover, NH
2008-2012 – Endocrine Physiology: part of the Physiology Course for 1st year medical students at Dartmouth Medical School, Hanover, NH
2013 – Lecturer, MHIR graduate course on Cell Biology of Tissue Development and Function, GSBSE Graduate Program, MHIR and the University of Maine
2014 – Lecturer, MHIR graduate course on Cell Biology of Tissue Development and Function, GSBSE Graduate Program, MHIR and the University of Maine
Spring 2015 – Endocrine Journal Club, GSBSE Graduate Program, MHIR and the University of Maine
Spring 2016 – Lecturer, MHIR graduate course on Cell Biology of Tissue Development and Function, GSBSE Graduate Program, MHIR and the University of Maine
Spring 2018 – Lecturer, MHIR graduate course on Cell Biology of Tissue Development and Function, GSBSE Graduate Program, MHIR and the University of Maine
Fall 2020 – “Epigenetics and Disease” Journal Club 630, GSBSE Graduate Program, MHIR and the University of Maine
Spring 2021 – “SARS-CoV-2 and COVID-19” Journal Club, GSBSE Graduate Program, MHIR and the University of Maine