Deborah Lang, Ph.D.

Transscription Factor Pax3, which Plays an Important Role During Development. Focus is on the Role of Pax3 in the Normal Maintainance of Adult Melanocyte Stem Cells and Disregulation in Melanoma Cells

Research Summary

Our lab studies the transcription factor Pax3, which plays an important role during development. We focus on the role of Pax3 in the normal maintainance of adult melanocyte stem cells and disregulation in melanoma cells.

Melanoma, one of the most common cancers in the United States, is projected to cause almost eight thousand deaths this year. The development of this tumor is not well understood, although it is thought to orginate from a rare melanocyte stem cell that resides in the skin. Recently, we have found Pax3 expressed by these uncommon melanocyte stem cells. The transcription factor Pax3 plays an important role in the development of the melanocyte during embryogensis. However, a role Pax3 in mature melanocytes has not been previously described.

In our recent report we describe a model where Pax3 acts as a molecular switch by promoting a melanocytic phenotype but blocks terminal differentiation. Our data suggests a model where Pax3 is down-regulated in response to terminal differentiation signals. Pax3 expression can then be maintained to promote pluripotency or repressed to induce differentiation. It may be these same mechanisms that promote the uncontrolled cell growth and loss of terminal differtiation in melanomas.

Selected Papers

Lang D, Miknyoczki SJ, Huang L, Ruggeri BA. (1998). Stable reintroduction of wild-type P53 (MTmp53ts) causes the induction of apoptosis and neuroendocrine-like differentiation in human ductal pancreatic carcinoma cells. Oncogene. 16(12):1593-602

Lang D, Chen F, Milewski R, Li J, Lu MM, Epstein JA. (2000). Pax3 is required for enteric ganglia formation and functions with sox10 to modulate expression of c-ret. Journal of Clinical Investigation 106:963-971

Lang D, Epstein JA. (2003). Sox10 and Pax3 physically interact to mediate activation of a conserved neural crest enhancer within the c-RET promoter. Human Molecular Genetics 12:(8)937-945

Lang D, Brown CB, Milewski R, Lu MM, Epstein JA. (2003). Regulation of Pax7 expression through upsteam and downstream enhancers. Genomics 82:(5)553-560

Lang D, Brown CB, Epstein JA. (2004). Neural Crest Formation and Craniofacial Development in Molecular Basis of Inborn Errors of Development, Charles Epstein, Robert Erickson and Anthony Wynshaw-Boris eds. Oxford University Press, San Francisco, CA.

Lang D, Lu MM, Huang L, Engleka K, Zhang M, Chu EY, Lipner S, Skoultchi A, Millar S and Epstein JA. (2005). Pax3 functions at a nodal point in adult melanocyte stem cell differentiation. Nature 433:884-7