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.
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.
Correa MC, Fonseca T, Molina J, Fachado A, Castillo M, Dong L, Soares R, Hernandez A, Caicedo A, Bianco AC (2014). Maternal inheritance of an inactive type III Deiodinase Gene affects mouse Pancreatic β-cells and disrupts Glucose Homeostasis. Endocrinology, 155 (8): 3160-3171.
Galton VA, de Waard E, Parlow AF, St. Germain DL, Hernandez A (2014) Life without the iodothyronine deiodinases. Endocrinology, 155: 3172-3181.
Charalambous M, da Rocha ST, Hernandez A, Ferguson-Smith AC (2014). Perturbations to the IGF1growth pathway and adult energy homeostasis following disruption of mouse chromosome 12 imprinting. Acta Physiol (Oxf) 210(1):174-87.
Galton VA, Hernandez A, St. Germain DL (2014). The 5¹-Deiodinases are Not Essential for the Fasting-induced Decrease in Circulating Thyroid Hormone Levels in Male Mice: Possible Roles for the Type 3 Deiodinase and Tissue Sequestration of Hormone. Endocrinology, 155 (8): 3172-3181.
Peeters RP, Hernandez A, Ng L, Ma M, Sharlin DS, Pandey M, Simonds W, St. Germain DL, Forrest D (2013). Cerebellar abnormalities in mice lacking type 3 deiodinase and partial reversal of phenotype by depletion of the thyroid hormone receptor α1. Endocrinology, 154 (1): 550-561.
Hernandez A, Morte B, Belinchon MM, Ceballos A, Bernal J (2012). Critical role of type 2 and 3 deiodinases in negative regulation of gene expression by T3 in the brain. Endocrinology, 153 (6): 2919-2928.
Charalambous M, Hernandez A (2012). Genomic imprinting of the type 3 thyroid hormone deiodinase gene: Regulation and developmental implications. Biochim. Biophys. Acta, in press.
Charalambous M, Ferron SR, da Rocha ST, Murray AJ, Rowland T, Ito M, Schuster-Gossler K, Hernandez A, Ferguson-Smith AC (2012). Imprinted gene dosage is critical for the transition to independent life. Cell Metabolism 15: 209-221.
- 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