The Mills laboratory is currently focused on assessing the role of tumor suppressor CHD5 in stem cells. They discovered that CHD5 functions as a tumor suppressor by serving as a master switch for a tumor suppressive network. CHD5 facilitates expression of Ink4/Arf, a locus that is also regulated by Bmi1, a protein that plays a key role in both neural and hematopoietic stem cells. Their findings suggest that CHD5 competes with Bmi1 to modulate stem cell fate/renewal. A second area of research interest is how the p53-related protein p63 affects cancer stem cells. Mills has shown that p63 depletion compromises proliferation by inducing a program of cellular senescence, thereby providing tumor protection while simultaneously contributing to aging. Current efforts are providing mechanistic insight into how p63 negatively impacts senescence to promote proliferation of epithelial stem cells, the cell type responsible for the most common human malignancy-carcinoma. These studies will help to elucidate the genetic basis of stemness.
Bagchi A, Mills AA. The quest for the 1p36 tumor suppressor. Cancer Res. 2008 Apr 15;68(8):2551-6. Review.
Mignone JL, Roig-Lopez JL, Fedtsova N, Schones DE, Manganas LN, Maletic-Savatic M, Keyes WM, Mills AA, Gleiberman A, Zhang MQ, Enikolopov G. Neural potential of a stem cell population in the hair follicle.
Cell Cycle. 2007 Sep 1;6(17):2161-70. Epub 2007 Jun 13.
Bagchi A, Papazoglu C, Wu Y, Capurso D, Brodt M, Francis D, Bredel M, Vogel H, Mills AA. CHD5 is a tumor suppressor at human 1p36. Cell. 2007 Feb 9;128(3):459-75.