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Melanocyte Pigmentation or Proliferation with Neuregulin: Compositions and Methods to Treat Skin Disorders, Including Skin Canc

Posted Aug 18 2010 5:00pm

Description of Invention:
Human skin pigmentation is regulated by complex and intricate interactions among melanocytes and keratinocytes in the epidermis and fibroblasts in the dermis. A number of factors secreted from keratinocytes and/or from fibroblasts have been shown to be involved in regulating skin pigmentation after UV exposure. NIH investigators have previously demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted factor (DKK1) that modulates Wnt signaling. Now, using microarray analysis to compare gene expression patterns in 15 different primary dermal fibroblast populations derived from the dorsal trunk skin of three different skin phototypes (I, III and VI), these investigators have identified a number of genes that differ dramatically in expression. One among them, neuregulin 1 (NRG-1), secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting it is one of the major factors determining human skin color. NRG-l was observed to be highly expressed by fibroblasts derived from darker skin. NIH investigators believe that NRG-1 increases the proliferation of human melanocytes via the phosphorylation of Akt. These results suggest a potential role for NRG-1 in regulating constitutive human skin color and perhaps its dysfunction in pigmentary skin diseases. Based on these observations, NIH investigators are currently developing compositions and methods of modulating pigmentation and proliferation of a melanocyte to prevent or treat skin disorders, including skin cancer.

Applications:
  • Therapeutics for skin disorders.
  • Therapeutics for skin cancer.


Development Status:
Early stage and studies on reconstructed skin model and in melanocytes.

Inventors:
Vincent J Hearing (NCI)
Wonseon Choi (NCI)


Patent Status:
HHS, Reference No. E-100-2010/0
US, Application No. 61/357,846 filed 23 Jun 2010


Relevant Publication:
  1. Choi W, Wolber R, Gerwat W, Mann T, Hearing VJ. Characterization of the influence of fibroblasts on melanocyte function and pigmentation. In: Proc. XXth Intl. Pigment Cell Conf., edited by K. Jimbow, Bologna, Italy: Medimond, 2008, p. 79-82.
  2. Choi W, Wolber R, Gerwat W, Mann T, Batzer J, Smuda C, Liu H, Kolbe L, Hearing VJ. A novel fibroblast-derived melanogenic paracrine factor neuregulin-1 (NRG-1) that modulates the constitutive color and melanocyte function in human skin. J. Cell Sci. in press, 2010.


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The Center for Cancer Research, Laboratory of Cell Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of NRG-1 (or modifiers of its function) to regulate skin pigmentation. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Therapeutics
Internal Medicine
Internal Medicine - Therapeutics



For Licensing Information Please Contact:
Suryanarayana Vepa Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vepas@mail.nih.gov
Phone: 301-435-5020
Fax: 301-402-0220


Ref No: 2146

Updated: 08/2010

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