GLUCOCORTICOIDS IN EPIDERMIS: MECHANISMS OF ACTION

Project: Research project

Project Details

Description

DESCRIPTION: (Adapted from the applicant's abstract) - This proposal focuses on
GCs, hormones that are important physiologic and pharmacologic regulators of
epidermal growth, differentiation, and homeostasis, and are extensively used in
treatment of both acute and chronic skin diseases. GCs inhibit wound healing
and immune responses and are growth inhibitory agents. However, the precise
molecular mechanism by which GCs perform their function is largely unknown. In
order to develop more effective treatment of cutaneous disorders with minimal
side effects, which is the investigator's long-term goal, she wishes to
understand how GCs operate in the skin. Towards this end, her current goal has
been to characterize the molecular mechanisms of corticosteroid regulation in
epidermis, specifically on the mechanisms by which GCs regulate keratin gene
expression. Keratins are phenotypic markers of epithelial development,
differentiation, and pathogenic states. The principal investigator and her
colleagues have generated data to show that certain hormones and vitamins, such
as GCs and retinoic acid, directly regulate keratin gene expression through
their nuclear receptors. The principal investigator found that the GC receptor
uses a novel mechanism for regulation of keratin gene expression. In this
proposal, the principal investigator wishes to define and characterize
precisely this novel mechanism. In the proposal, the principal investigator
plans to characterize the molecular interactions between the GC receptor and
the recognition sites for the receptor on keratin genes. Second, she plans to
define the particular regions of the GC receptor involved in these
receptor-gene interactions. Third, she wishes to define co-regulators (other
interactive proteins) involved in the interaction between the GC receptor and
keratin genes. The principal investigator believes that the experiments planned
will generate new insights and knowledge to provide an understanding of the
mechanism of action of the GC receptor, an important transcription factor for
keratin gene expression, and, in particular, its effects in skin. This new
knowledge could lead to the development of better treatments of patients with
cutaneous disorders, treatments that are more effective, have less side
effects, and are targeted to address the causes of the disease and not just
alleviate the symptoms.
StatusFinished
Effective start/end date7/1/006/30/06

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $185,357.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $195,850.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $201,724.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $186,151.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $190,534.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.