U.S. Department of Health and Human Services
Douglas Forrest
 

 Contact Info

 
Tel: 301-594-6170
Email: df189j@nih.gov
 

 Select Experience

 
  • Senior InvestigatorNIDDK, NIH2004
  • Associate ProfessorMount Sinai School of Medicine, Department of Human Genetics1995–2004
  • Ph.D.Glasgow University1987
 

 Related Links

 

    Specialties
    • Developmental Biology
    • Endocrinology
    • Genetics/Genomics
    • Molecular Biology/Biochemistry
    • Neuroscience/Neurophysiology/Neurodevelopment

    Research Summary

    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 in both 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 genes that cooperate with the receptor genes to determine cell-specific responses. For example, it has been found that genes encoding deiodinase enzymes that control the availability of thyroid hormone in specific tissues are critical determinants in differentiation.

    Our studies include investigation of thyroid hormone receptor functions in the development of sensory systems, including 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 thyroid hormone signaling is critical for generating the cone photoreceptor diversity that determines color visual functions in mammalian species. 

    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 both 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.