Douglas Forrest, Ph.D.

Senior Investigator

Nuclear Receptor Biology Section, Laboratory of Endocrinology and Receptor Biology

NIDDK

Building 10, Room 8N307
10 Center Drive
Bethesda, MD 20814

301-594-6170

df189j@nih.gov

Research Topics

Research Goal

Thyroid hormone has numerous functions both in development and in homeostasis, the body’s ability to maintain internal stability.  Although thyroid hormone is known to elicit powerful responses in the body, we do not fully understand how this happens or how disease arises when these controls become faulty.  It is therefore necessary to elucidate the mechanisms by which thyroid hormone elicits its cell-specific actions as a prerequisite to understanding the basis of thyroid disease.  Ultimately, this knowledge may aid in the design of improved treatments for thyroid disease.   

Current Research

Thyroid hormone controls diverse functions both in development and in adult homeostasis in vertebrate species. In humans, congenital thyroid hormone abnormalities may result in neurodevelopmental and physical retardation, whereas abnormalities in adulthood result in a range of other forms of impairment. Using genetic approaches, we aim to elucidate the mechanisms that regulate where, when, and how thyroid hormone acts and to uncover new functions for this hormone.

Thyroid hormone receptors are nuclear receptors that act as ligand-regulated transcription factors and control a critical point at which the hormonal signal is converted into a cellular response. We investigate how thyroid hormone receptors mediate specialized functions in the endocrine system, nervous system, and other systems of the body. We also investigate other factors that determine cell-specific responses. These factors include deiodinase enzymes that control the availability of thyroid hormone in specific tissues may be critical determinants in differentiation.

Our studies include investigation of thyroid hormone receptors in sensory development, including in the auditory and visual systems. We identified a specific receptor isoform in the retina, which proved to be unexpectedly critical for the development of the light-sensitive photoreceptors that mediate vision. Genetic studies indicated that this thyroid hormone receptor is critical for generating the cone photoreceptor diversity that determines color visual functions and moreover, also contributes to the death or survival of cone photoreceptors. 

We also investigate other nuclear receptors in mammalian development, including retinoid-related orphan receptors. The study of nuclear receptors, which act as ligand-regulated transcription factors, should reveal how networks of transcriptional responses mediate specific biological processes.

Applying our Research

Thyroid diseases are common in the human population. For example, impaired thyroid function occurs in about one in 2,500 newborns and can result in mental and physical retardation. In adults, impaired thyroid function can produce a range of other types of symptoms (for example, in metabolism and cardiac function). Although thyroid hormone is known to control powerful responses in the body, we do not understand fully how this happens, or how disease arises when these controls become faulty. Research to uncover how thyroid hormone controls the development of different tissues and subsequently how this hormone maintains normal function throughout adult life is therefore necessary for understanding the basis of thyroid disease. Ultimately, such knowledge may aid in the design of improved treatment of disease.

Biography

  • Senior Investigator, NIDDK, NIH, 2004
  • Associate Professor, Mount Sinai School of Medicine, Department of Human Genetics, 1995–2004
  • Ph.D., Glasgow University, 1987

Selected Publications

  1. Ng L, Kelley MW, Forrest D. Making sense with thyroid hormone--the role of T(3) in auditory development. Nat Rev Endocrinol. 2013;9(5):296-307.

  2. Liu H, Kim SY, Fu Y, Wu X, Ng L, Swaroop A, Forrest D. An isoform of retinoid-related orphan receptor β directs differentiation of retinal amacrine and horizontal interneurons. Nat Commun. 2013;4:1813.

  3. Huang CC, Kraft C, Moy N, Ng L, Forrest D. A Novel Population of Inner Cortical Cells in the Adrenal Gland That Displays Sexually Dimorphic Expression of Thyroid Hormone Receptor-β1. Endocrinology. 2015;156(6):2338-48.

  4. Swaroop A, Kim D, Forrest D. Transcriptional regulation of photoreceptor development and homeostasis in the mammalian retina. Nat Rev Neurosci. 2010;11(8):563-76.

  5. Ng L, Lyubarsky A, Nikonov SS, Ma M, Srinivas M, Kefas B, St Germain DL, Hernandez A, Pugh EN Jr, Forrest D. Type 3 deiodinase, a thyroid-hormone-inactivating enzyme, controls survival and maturation of cone photoreceptors. J Neurosci. 2010;30(9):3347-57.


This page was last updated on November 2nd, 2017