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James
M. Grichnik, M.D., Ph.D.
(Harvard Medical School)
Assistant Professor,
Departments of Medicine (Dermatology) and Cell Biology
Programs: Duke Comprehensive Cancer Center, Cancer Biology
Study Program
Director, Melanocytic Diseases Section
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Genetic
defects of the KIT receptor or its ligand, stem cell factor
(SCF; also known as steel factor or mast cell growth factor),
result in the loss of cutaneous melanocyte precursors
during murine development. In humans, a defect in a single
allele of the c-KIT gene has been noted in patients with
congenital amelanocytic patches (piebaldism) suggesting
that this pathway also functions in the survival of human
melanocytes. We have established that stimulation of KIT
results in human melanocytic proliferation and expression
of the "melanoma-associated-antigen" identified
by the monoclonal antibody HMB-45. Further, inhibition
of the KIT receptor with an inhibitory antibody, K44.2,
appears to result in melanocyte loss. This pathway clearly
plays a critical role in proliferation control of normal
melanocytes but it's role in early melanoma tumor development
remains to be defined. In advanced melanoma tumors, KIT
is often down-regulated and this may allow tumors to escape
its growth-controlling properties. Modulators of the KIT
pathway may have therapeutic value in the treatment of
melanoma. |
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E-mail
grich001@mc.duke.edu
4032 Hospital South, Box 3135
Duke University Medical Center
Durham, NC 27710
Telephone 919-684-3270
Fax 919-684-3002 |
Selected
Publications
Grichnik, J, Burch, J, Burchette J and Shea C. Stem Cell
Factor/KIT pathway plays a critical role in the control
of normal human melanocyte homeostasis. J Invest Derm
1998; 111:233-238
Wallace M, Grichnik J, Priota V, Shea C. Differentiation
Antigen vs Cellular Loss of Melanocytes in Idiopathic
Guttate Hypomelanosis. J Cutan Pathol 1998;25:375-9
Whited J. and Grichnik J. Rational Physical Examination:
Does this patient have a mole or a melanoma? JAMA 1998;
279(9):696-701
Grichnik JM, Ali WN, Burch JA, Byers JD, Garcia CA, Clark
RE, Shea CR: KIT expression reveals a population of precursor
melanocytes in human skin. J Invest Dermatol 1996;106(5):967-971
Grichnik JM, Crawford J, Jimenez F, Kurtzberg J, Buchanan
M, Blackwell S, Clark RE, Hitchcock MG. Human recombinant
stem cell factor induces melanocytic hyperplasia in susceptible
patients. J Amer Acad Derm 1995;33:577-583 |
Current
Projects
Laboratory efforts are currently focused on:
1) regulation of the KIT receptor in normal melanocytes
and melanoma cells
2) identification of agents that modulate KIT receptor
levels, and
3) the study of the effects of KIT inhibition on xenografted
human melanocytic tumors. |
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