Cellular events which mediate thyroid hormone action in development and pathophysiology
1974 B.S., Biology and Psychology cum laude; Boston College, Chestnut Hill MA.
1980 Ph.D., Physiology & Biophysics/Molecular Endocrinology University of Illinois Medical Center Chicago IL
1980-1983 Postdoctoral Research Fellow, Division of Endocrinology, U Minnesota, Minneapolis MN
1983-1984 Research Fellow in Medicine, Massachusetts General Hospital, Harvard Medical School Boston MA
2005-present Professor, Department of Pharmacology, College of Medicine, Member-Vermont Cancer Center, University of Vermont, Burlington VT
1999-2005 Professor, Department of Biological Sciences, Binghamton University, State University of New York, Binghamton NY
1992-1999 Associate Professor (adjunct), Department of Pharmacology; Research Associate Professor, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD
1987-1993 Director, Endocrine Research Division-Kyle Metabolic Unit, Department of Clinical Investigation, Walter Reed Army Medical Center, Washington DC
1987-1992 Assistant Professor (adjunct), Department of Physiology; Research Assistant Professor, Department of Medicine, Uniformed Services University of Health Sciences, Bethesda MD
1985-1987 Associate, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston MA
1986-1987 Instructor, Department of Physiology and Biophysics, Harvard Medical School, Boston MA
1983-1987 Instructor in Medicine, Harvard Medical School, Boston MA
1981-1983 Instructor, Department of Physiology, University of Minnesota, Minneapolis, MN
1978-1980 Instructor, Department of Physiology and Biochemistry, Illinois College of Podiatric Medicine, Chicago, IL
Thyroid hormones are essential for coordinated fetal and neonatal growth and development, as well as metabolic, reproductive and cardiovascular functions throughout life. The diverse physiological effects of thyroid hormones are mediated through cellular events that may be initiated within the cell nucleus, the plasma membrane, the mitochondrion and the cytoplasm. The overall goal of the research program in the Carr lab is to understand the cellular events which mediate thyroid hormone action in development and pathophysiology, thyroid cancer.
Environmental toxins, by disrupting endocrine function, have emerged as a major public health issue. Endocrine disrupting chemicals with structural similarities to steroid and thyroid hormones have been shown to mimic or antagonize hormone action at the cellular level resulting in disruption of a complex array of genomic and non-genomic events resulting in discordant reproductive development, impaired neurodevelopment, disruption of thyroid homeostasis and an increase in endocrine-related cancers. The goals or our endocrine disruption program in environmental carcinogenesis are to 1) determine the intracellular mechanism(s) of disruption of thyroid hormone action in pituitary and thyroid tumor cells and 2) elucidate the impact on the etiology of thyroid cancer in tumor cells and tumor biomarkers in thyroid cancer clinical studies. To determine the impact of selected toxins on thyroid hormone mediated cellular processes, the laboratory uses a variety of biochemical, molecular, proteomic, and microarray techniques. Our recent studies in pituitary tumor cells revealed that bisphenol A (BPA) and DDE, a metabolite of the pesticide DDT, in part through disruption of the thyroid hormone receptor (TR) within the nucleus, alter cell proliferation as well as gene expression (Zakrzewska et al. 2010). Through proteomic analysis and expression arrays, we are determining the functional significance of toxin disruption of the nuclear protein complex assembly with the thyroid hormone receptor (TR) that mediates thyroid hormone effects on gene regulation. We are also determining whether selected toxins alter plasma membrane (integrin) mediated changes in intracellular signaling including MAPK, PI3K phosphorylation of the TR to induce a cellular mislocation of the TR to impede gene regulation and tumor suppression as detected by IF and confocal microscopy. We have recently characterized the molecular phenotypes of benign thyroid cells and differentiated and de-differentiated thyroid cancers (Zakrzewska et al. 2008). The lab is determining the impact of selected environmental toxins on selected biomarkers, cell motility, cell invasion and microRNA profiles in human thyroid cancer cell lines and thyroid tumors.
Zakrzewska EI, McKenzie A, White JH, Carr FE. Environmental toxins, bisphenol A (BPA) and dichlorodiphenyoldichloroethylene (DDE), disrupt thyroid hormone mediated events in rat pituitary GH3 cells. 14TH International Thyroid Congress, Paris, 2010.
Zakrzewska EI, Bond JP, Carr FE. Microarray-based identification of putative biomarkers in follicular, papillary and anaplastic thyroid cancer. American Thyroid Association, Chicago IL, 2008.
Carome MA, Kang Y-H, Bohen EM, Nicholson DE, Carr FE, Kiandoli LC, Brummel SE, Yuan CM. Distribution of the cellular uptake of phosphorothioate oligodeoxynucleotides in the rat kidney in vivo. Kidney. 75:82-87, 1997.
Dong Q, Brucker-Davis F, Weintraub BD, Smallridge RC, Carr FE, Battey J, Spiegel AM, Shenker A. Screening of candidate oncogenes in human thyrotroph tumors: absence of activating mutations of the G alpha q, G alpha 11, G alpha s or thyrotropin-relasing hormone receptor genes. Journal of Clinical Endocrinology and Metabolism. 81:1134-1140, 1996.
Kiang JG, Carr FE, Burns MR, McClain D. HSP-72 synthesis is promoted by increase in [Ca2+]i or activation of G proteins but not pHi or cAMP. Am J Physiol 267:c104-14, 1994.
* indicates equal contribution
Meritorious Honor Award-U.S. Agency for International Development (1996)
Recipient of seven U.S. government Outstanding Performance Awards (1987-1994)
National Research Service Award, National Institutes of Health (1980-1983)
Sigma Xi Graduate Research Forum, First Awards (1979 & 1980)
Department of Pharmacology
Office: HSRF 318
Lab: C444 Given
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