|SOM Address||544 Cancer Research Building I|
Kurtis Bachman 1996 – 2000
Xiaobei Zeng 1996 – 2002
Virote Sriurangpong 1997 – 2001
Eric Nakakura 1998 – 2001
Sayaka Eguchi 1999 – 2006
Brian Reese 1999 – 2004
Jill Fahrner 2000 – 2004
Angela Ting 2001 – 2005
Kimberly Briggs 2002 – 2008
Kelly McGarvey 2002 – 2007
Eriko Greene Clements 2003 – 2011
David Wang 2003 – 2010
Molecular Determinants of Tumor Progression
Our laboratory group studies the molecular determinants of altered cellular differentiation in the evolution of selected human tumors. One focus involves delineating how differentiation features are lost from endocrine tumors during progression. Transcription factors that mediate peptide hormone gene expression are being defined and their role in mediating the endocrine cell phenotype is under study. Gene insertion studies are used to delineate the signal transduction steps that guide endocrine differentiation.
We have shown that, in human tumors, abnormal hypermethylation of CpG rich promoter regions is associated with loss of important tumor suppressor gene expression during tumor progression. We are continuing to define the genes involved with this alteration and to investigate the mechanisms underlying appearance of the methylation changes. Regulation of DNA methylation is being studied by characterization of the human DNA methyltransferase gene and the effects of its over and under expression in eukaryotic cells. To understand the role of abnormal methylation patterns, we are delineating, in experimental systems and selected human tumors, the relationships between abnormal DNA methylation sites, time of their appearance during tumor evolution and consequences for specific chromosome changes and gene expression events.
- Rhee I, Bachman KE, Park BH, Jair KW, Yen RW, Schuebel KE, Cui H, Feinberg AP, Lengauer C, Kinzler KW, Baylin SB, and Vogelstein B.DNMT1 and DNMT3b cooperate to silence genes in human cancer cells.Nature, 416: 552-556, 2002.
- Suzuki H, Gabrielson E, Chen W, Anbazhagan R, van Engeland M,Weijenberg MP, Herman JG, and Baylin SB. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in humancolorectal cancer. Nat Genet, 31: 141-149, 2002.
- Chen WY, Zeng X, Carter MG, Morrell CN, Yen, RW, Esteller M,Watkins DN, Herman JG, Mankowski JL, and Baylin SB. Heterozygousdisruption of Hic1 predisposes mice to a gender-dependent spectrum ofmalignant tumors. Nat Genet, 33: 197-202, 2003.
- Watkins DN, Berman DM, Burkholder SG, Wang B, Beachy P, Baylin SB.Hedgehog signaling within airway epithelial progenitors and small cell lung cancer.Nature, 422: 313-317, 2003.