My research experience began with laboratory projects at Occidental College in Los Angeles. During my residency and fellowship training at Boston University Medical Center (BUMC), I undertook several clinical research projects with Drs. Lewis Braverman and Elizabeth Pearce. In June 2009, I completed a clinical and research fellowship in the Section of Endocrinology, Diabetes, and Nutrition at Boston University Medical Center (BUMC), the last 2 years of which were supported by an NIH T32 National Research Service Award. I completed the BUMC Clinical Research Training (CREST) program (an NIH K30 Clinical Research Curriculum Award) from 2007-2009. In July 2009, I became a junior faculty member at Boston University, a Clinical and Translational Institute (CTSI) site, (BU-BRIDGE). I received a Master of Science in Epidemiology degree at the Boston University School of Public Health in January 2010. I have had 5 original research publications related to the topics of the current proposal, including 3 as first author. I am supported by a Charles A. King Trust Postdoctoral Fellowship Award and an NIH K12 Building Interdisciplinary Research Careers in Women's Health (BIRCWH) grant at Boston University. The BIRCWH scholars program promotes career development of young investigators through mentored research, monthly research meetings, academic guidance, and national research presentations. During the K23 award period, my career development plans include participation in research-oriented seminars, presenting at national endocrine meetings, attending BUMC didactic conferences, teaching activities, and formal coursework at BUMC. I have assembled a research advisory committee who will assess my progress and provide ongoing guidance as I pursue my research plan. The skills and mentorship I will obtain through the BIRCWH and K23 awards will allow me to develop future research hypotheses aimed at specific strategies of achieving adequate iodine nutrition and normal thyroid function during pregnancy and lactation. This work will then prepare me to embark on the design and implementation of an R01 award aimed at specific strategies to achieve universal adequate iodine nutrition and normal thyroid function during pregnancy and lactation. Environment I am currently an Instructor of Medicine in the Section of Endocrinology, Diabetes, and Nutrition (Shalender Bhasin, MD;Chief) at BUMC, where the majority of my current appointment is devoted to research. The Section is comprised of 45 full-time faculty members (including one of the largest thyroid groups in the country with 7 fulltime MD faculty) and boasts over 12 million dollars in research funding, an NIH training grant, and several program and center projects. My mentor on this proposal is Dr. Lewis Braverman, Professor of Medicine at BUMC and an accomplished mentor to over 60 fellows in various aspects of thyroid physiology over his nearly 50-year career. My co-mentor is Dr. Elizabeth Hatch, Associate Professor of Epidemiology at Boston University School of Public Health, who has extensive experience and research interests in prenatal and childhood exposures relating to adverse reproductive outcomes. Research Iodine deficiency is debilitating, prevalent, and the leading cause of mental retardation worldwide. Dietary iodine is necessary for thyroid hormone synthesis. Normal thyroid function is particularly important during pregnancy and lactation, as maternal thyroid hormone levels are crucial for proper fetal and infant neurodevelopment. The impact of breast milk iodine levels on infant thyroid function is unknown. In addition, environmental exposures to perchlorate and cigarette smoke (which is metabolized to thiocyanate) decrease iodine uptake into the lactating breast, thereby further impairing iodine availability to the infant and potentially directly affecting infant thyroid function. The broad objective of this proposal is to test the hypotheses that: 1) hypothyroidism during pregnancy is associated with premature birth and other adverse obstetric/perinatal outcomes, and 2) breast milk perchlorate and thiocyanate levels, by their inhibition of NIS, decrease breast milk iodine levels (which fluctuate in relationship to dietary iodine ingestion), and are associated with infant hypothyroidism. The results of this research will have important public health implications for thyroid function screening among pregnant women and adequate maternal iodine nutrition during pregnancy and lactation.
Specific Aim 1 will be a database review studying the relationships between maternal hypothyroidism during pregnancy and obstetric/perinatal outcomes.
Specific Aim 2 will be an interventional assessment of an iodine load on the effects and timing of peak breast milk iodine levels in postpartum women.
Specific Aim 3 will be a cross-sectional study of maternal and infant iodine intake, maternal and infant perchlorate and cigarette smoke (thiocyanate) exposures, and infant thyroid function. The pursuit of these projects, in conjunction with formal coursework in biostatistical and epidemiological methods, is intended to foster my career as an independent academic clinical investigator in thyroid disease as it relates to women's and infant health.

Public Health Relevance

Iodine is necessary for thyroid hormone synthesis. Normal thyroid function, which requires adequate dietary iodine intake, is particularly important during pregnancy and lactation, as maternal thyroid hormone levels are crucial for proper fetal and infant neurodevelopment. The impact of breast milk iodine levels on infant thyroid function is unknown. This proposal will study maternal thyroid function and pregnancy outcomes, and in lactating women, the relationships between iodine nutrition and environmental exposures which may decrease the ability to use iodine.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Raiten, Daniel J
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Boston University
Internal Medicine/Medicine
Schools of Medicine
United States
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Leung, Angela M; Pearce, Elizabeth N; Braverman, Lewis E (2014) Environmental perchlorate exposure: potential adverse thyroid effects. Curr Opin Endocrinol Diabetes Obes 21:372-6
Labadzhyan, Artak; Brent, Gregory A; Hershman, Jerome M et al. (2014) Thyrotoxicosis of Pregnancy. J Clin Transl Endocrinol 1:140-144
Willard, Devina L; Leung, Angela M; Pearce, Elizabeth N (2014) Thyroid function testing in patients with newly diagnosed hyperlipidemia. JAMA Intern Med 174:287-9
Leung, Angela M; Braverman, Lewis E (2014) Consequences of excess iodine. Nat Rev Endocrinol 10:136-42
Thaker, V V; Leung, A M; Braverman, L E et al. (2014) Iodine-induced hypothyroidism in full-term infants with congenital heart disease: more common than currently appreciated? J Clin Endocrinol Metab 99:3521-6
Fast, Søren; Hegedüs, Laszlo; Pacini, Furio et al. (2014) Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study. Thyroid 24:727-35
Leung, Angela M; Katz, Pamela M; He, Xuemei et al. (2014) Urinary perchlorate and thiocyanate concentrations in pregnant women from Toronto, Canada. Thyroid 24:175-6
Katz, Pamela M; Leung, Angela M; Braverman, Lewis E et al. (2013) Iodine nutrition during pregnancy in Toronto, Canada. Endocr Pract 19:206-11
Pearce, Elizabeth N; Leung, Angela M (2013) The state of U.S. Iodine nutrition: how can we ensure adequate iodine for all? Thyroid 23:924-5
Pramyothin, Pornpoj; Leung, Angela M; Pearce, Elizabeth N et al. (2011) Clinical problem-solving. A hidden solution. N Engl J Med 365:2123-7

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