Professor Garrett-Sinha is interested in the role of Ets proteins in regulating the normal development of hematopoietic cells, and the role of Ets family members in tumor formation and progression. Ets-1 is one of the Ets genes that has been shown to be over-expressed in a large number of different types of human cancers. Human tumors that over-express Ets-1 tend to be more aggressive and metastatic than Ets-1 negative tumors. To explore the relationship between Ets-1 expression and tumor formation and metastasis, this lab has recently developed a transgenic mouse model in which they can inducibly express Ets-1 in a variety of tissues at different stages of development. The induction of Ets-1 in the epithelial cells of stratified squamous epithelial tissues in adult mice resulted in a dramatic hyper-proliferative phenotype and altered terminal differentiation of the tissues. These results support a role for Ets-1 in mediating early events in squamous cell carcinogenesis.
John SA, Clements JL, Russell LM, Garrett-Sinha LA. Ets-1 regulates plasma cell differentiation by interfering with the activity of the transcription factor Blimp-1. J Biol Chem. 2008 Jan 11;283(2):951-62. Epub 2007 Oct 31.
Clements JL, John SA, Garrett-Sinha LA. Impaired generation of CD8+ thymocytes in Ets-1-deficient mice. J Immunol. 2006 Jul 15;177(2):905-12.
Wang D, John SA, Clements JL, Percy DH, Barton KP, Garrett-Sinha LA. Ets-1 deficiency leads to altered B cell differentiation, hyperresponsiveness to TLR9 and autoimmune disease. Int Immunol. 2005 Sep;17(9):1179-91. Epub 2005 Jul 28.