- Staff Scientist, NIDDK, NIH, 2004–Present
- Research Assistant Professor, Department of Human Genetics, Mount Sinai School of Medicine, 1997–2004
- Ph.D., State University of New York at Stony Brook, 1991
One of the most important functions for thyroid hormone is to stimulate the development and function of immature tissues. However, much remains unknown about the specific actions of this hormone in the different cell types and tissues in the body. We study thyroid hormone receptors to reveal critical steps in development and to gain important insights into the underlying mechanisms of cellular differentiation and function.
My research is focused on the neurodevelopmental functions of thyroid hormone receptors. These receptors control cellular responses via the regulation of gene expression and belong to a wider family of nuclear receptors that act as ligand-dependent receptors. We use molecular biology and genetic analysis to gain insights into how thyroid hormone receptors and other factors regulate development in mammalian systems. We have found that sensory systems are particularly dependent on thyroid hormone receptors. We investigate novel roles of these receptors in the auditory and visual systems.
In addition to thyroid hormone receptors, we also study the deiodinase enzymes that metabolize thyroid hormone into active or inactive forms. There is growing awareness that development requires not only appropriate levels of thyroid hormone in the circulation but also the ability to modify the level of active hormone in target tissues. Deiodinases play a major role in determining thyroid hormone availability in tissues. We investigate the role of deiodinases in development of different tissues including critical functions in the eye and the inner ear, the sensory organs for vision and hearing.
Applying our Research
The development and maintenance of the nervous system is important for health. Thyroid disorders can lead to retarded development if untreated. There is a lack of knowledge of how thyroid hormone stimulates the development of many tissues at the cellular level. Our research addresses this need to understand the actions of thyroid hormone in development. Advances gained by research that improve our knowledge of the actions of thyroid hormone may lead to better insights into the developmental defects that arise in thyroid disorders.
Retarded development of the brain can impair mental function, and retarded development of the eye or inner ear can impair sensory function. Understanding the contribution of thyroid hormone to the development and function of the nervous system is essential for providing information that could help in the design of future treatments for neurodevelopmental disorders.
Need for Further Study
It is known that developmental thyroid disorders in humans present a risk to different tissues including in the nervous system. However, our understanding of what thyroid hormone does at the cellular and molecular level is far from complete. A crucial question concerns the need to identify the cellular responses and the downstream target genes that are regulated by thyroid hormone receptors in different tissues. Research to address these questions would reveal regulatory mechanisms of these receptors and would provide key insights that will help us understand how thyroid hormone receptors control cellular differentiation and function.
- Deafness and loss of cochlear hair cells in the absence of thyroid hormone transporters Slc16a2 (Mct8) and Slc16a10 (Mct10).
- Sharlin DS, Ng L, Verrey F, Visser TJ, Liu Y, Olszewski RT, Hoa M, Heuer H, Forrest D.
- Sci Rep (2018 Mar 13) 8:4403. Abstract/Full Text
- SKP2 Activation by Thyroid Hormone Receptor β2 Bypasses Rb-Dependent Proliferation in Rb-Deficient Cells.
- Xu XL, Li Z, Liu A, Fan X, Hu DN, Qi DL, Chitty DW, Jia R, Qui J, Wang JQ, Sharaf J, Zou J, Weiss R, Huang H, Joseph WJ, Ng L, Rosen R, Shen B, Reid MW, Forrest D, Abramson DH, Singer S, Cobrinik D, Jhanwar SC.
- Cancer Res (2017 Dec 15) 77:6838-6850. Abstract/Full Text
Research in Plain Language
Thyroid hormone is a powerful stimulus for development of different tissues including a particularly important role in the nervous system. However, there is a gap in our understanding of the actions of thyroid hormone at the cellular level in target tissues. Our research addresses this need to elucidate how thyroid hormone stimulates development. We investigate the functions of thyroid hormone receptors, which are the crucial proteins within cells that bind the hormone and mediate the cellular response. We also investigate deiodinase enzymes that convert thyroid hormone into active and inactive forms in different tissues and thereby provide another critical level of control over the response to thyroid hormone.