RAB38, a Target for Treatment of Melanoma and Pigmentation Disorders
Description of Invention:
Melanocytes are specialized pigment-producing cells that are responsible for coloration of skin, eyes and hair. Using cDNA microarray expression profiling, the inventors have identified RAB38, a small GTP-binding protein, as an important gene involved in melanocyte function. Human RAB38 was localized to the mouse chocolate (cht) locus, and mutation of this gene in mice changes hair color from black to brown, similar to OCAIII mice, which have a mutation in TYRP1, another melanosomal gene, and are used as a model for oculocutaneous albinism.
The inventors have demonstrated that RAB38 is important for trafficking of the TYRP1 protein; thus, RAB38 mutant mice are genocopies of TYRP1 mutant mice. Modulation of RAB38 activity, such as by pharmacologic intervention, might alter pigmentation in human skin. Recently, RAB38 has also been identified as a melanocyte differentiation antigen that is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. Thus, RAB38 may also have applications for melanoma diagnostics and treatment.
This invention discloses RAB38 nucleic acids and protein, and methods for detecting mutations in RAB38. Also disclosed are methods for screening for agents to modulate RAB38 activity, and for modulating pigmentation through modulation of RAB38 activity.
Applications:
Marker protein and target for antigen-specific immunotherapy in patients with malignant melanoma.
Therapeutics and diagnostics for melanin-related disorders.
Patent Status:
DHHS Reference No. E-315-2001/0 --
U.S. National Stage Application No. 10/501,611 filed 20 Nov 2005, claiming priority to 18 Jan 2002
Foreign counterparts pending in Australia, Canada, Europe, and Japan
Relevant Publication: Stacie K. Loftus, Denise M. Larson, Laura L. Baxter, Anthony Antonellis, Yidong Chen, Xufeng Wu, Yuan Jiang, Michael Bittner, John A. Hammer III, and William J. Pavan. Mutation of melanosome protein RAB38 in chocolate mice. Proc Natl Acad Sci U.S.A. 2002 Apr 2;99(7):4471-4476. [PubMed abs]
Licensing Status: This technology is no longer available for licensing.
Portfolios: Rare Diseases Internal Medicine Cancer
Internal Medicine-Diagnostics-Skin Disorders Internal Medicine-Therapeutics-Skin Disorders Cancer -Diagnostics Cancer -Therapeutics Internal Medicine-Diagnostics Internal Medicine-Therapeutics
For Additional Information Please Contact: Charlene A. Sydnor Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-4689
Email: sydnorc@mail.nih.gov
Fax: 301/402-0220
