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Alea A. Mills

Alea A. Mills

Professor

Ph.D., University of California, Irvine, 1997

mills@cshl.edu | (516) 367-6910

Cells employ stringent controls to ensure that genes are turned on and off at the correct time and place. Accurate gene expression relies on several levels of regulation, including how DNA and its associated molecules are packed together. I study the diseases arising from defects in these control systems, such as aging and cancer.

Alea Mills is studying genetic pathways important in cancer, aging, and autism, identifying the genetic players and determining how aberrations in their functions culminate in human disease. Through innovative use of a technique called “chromosome engineering,” the Mills group discovered that one of the most common genetic alterations in autism—deletion of a 27-gene cluster on chromosome 16—causes autism-like features in mice. These autism-like movement impairments can be identified just days after birth, suggesting that these features could be used to diagnose autism. Mills has also used chromosome engineering to identify a tumor suppressor gene that had eluded investigators for three decades. The gene, called Chd5, was shown by Mills to regulate an extensive cancer-preventing network. This year, the Mills lab uncovered how Chd5 acts as a tumor suppressor: It binds to a protein found within chromatin to turn specific genes on or off, halting cancer progression. The epigenetic role of Chd5 in development, cancer, and stem-cell maintenance is currently being investigated. The Mills lab is also studying p63 proteins, which regulate development, tumorigenesis, cellular senescence, and aging in vivo. They succeeded in halting the growth of malignant tumors by turning on production of one of the proteins encoded by the p63 gene, called TAp63. TAp63 also exerts other protective effects. This year, the Mills lab generated a mouse model which allowed them to find that TAp63 is required to prevent a genetic disorder, known as EEC (ectrodactyly-ectodermal dysplasia cleft lip/palate syndrome), which is characterized by a cleft palate and major deformities of the skin and limbs in infants. In addition, they recently discovered that a different version of p63, called ΔNp63, reprograms stem cells of the skin to cause carcinoma development—the most prevalent form of human cancer. Modulation of these proteins may offer new ways to treat human malignancies in the future.

Woman of the Year in Health/Medicine – 2012

Keyes, W. M. and Pecoraro, M. and Aranda, V. and Vernersson-Lindahl, E. and Li, W. and Vogel, H. and Guo, X. and Garcia, E. L. and Michurina, T. V. and Enikolopov, G. N. and Muthuswamy, S. K. and Mills, A. A. (2011) DeltaNp63alpha Is an Oncogene that Targets Chromatin Remodeler Lsh to Drive Skin Stem Cell Proliferation and Tumorigenesis. Cell Stem Cell, 8(2) pp. 164-76.

Mills, A. A. (2010) Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins. Nat Rev Cancer, 10(10) pp. 669-82.

Guo, X. and Keyes, W. M. and Papazoglu, C. and Zuber, J. and Li, W. and Lowe, S. W. and Vogel, H. and Mills, A. A. (2009) TAp63 induces senescence and suppresses tumorigenesis in vivo. Nat Cell Biol, 11(12) pp. 1451–1457.

Bagchi, A. and Mills, A. A. (2008) The quest for the 1p36 tumor suppressor. Cancer Res, 68(8) pp. 2551-6.

Additional materials of the author at
CSHL Institutional Repository