Alea A. Mills
Professor
Ph.D., University of California, Irvine, 1997
mills@cshl.edu | (516) 367-6910 (p)
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
Portrait of a Neuroscience Powerhouse
April 27, 2018
At noon every Tuesday from September through June, scenes from a revolution in neuroscience are playing out at Cold Spring Harbor Laboratory. Week after week, over 100 scientists cram themselves into a ground-floor meeting room in the Beckman Laboratory. It’s standing-room only as everyone in the Neuroscience Program settles in to hear details of the...
Partners Profile: High School Senior Tamanna Bhatia on becoming a scientist
January 26, 2016
LabDish blog Written by Marygrace Navarra, CSHL Human Resources Assistant The young scientists in CSHL’s Partners for the Future Program have a real impact—not only by conducting research in the lab, but also by inspiring the people they meet. When 18-year-old Tamanna Bhatia came to the Human Resources office at CSHL to hand in some...
12th annual LI2DAY Walk raises over $400,000
September 1, 2015
Cold Spring Harbor, NY – Cold Spring Harbor Laboratory (CSHL) is among 17 Long Island-based organizations to receive funding from the 2015 Long Island 2 Day Walk to Fight Breast Cancer. This year’s walk raised over $400,000 for outreach services, educational programs and research to benefit women and their families affected by breast and other...
Male infertility: it’s all about the package
May 13, 2014
Scientists find a protein that controls DNA organization during sperm development Cold Spring Harbor, NY – Infertility is generally thought of as a woman’s problem. In fact, more than 3 million men across America also experience it. Today, researchers from Cold Spring Harbor Laboratory (CSHL) describe a key event during sperm development that is essential...
CSHL geneticists solve mystery of EEC Syndrome’s variable severity in children
June 14, 2013
Proteins called TAp63 act as genetic modifiers in an illness that produces cleft palate and major deformities of limbs, skin Cold Spring Harbor, NY — By identifying a protein that acts as a genetic modifier, scientists at Cold Spring Harbor Laboratory (CSHL) have solved the mystery of why some infants are born with a grave...
Cancer scientists determine mechanism of one of the most powerful tumor-suppressor proteins, Chd5
January 10, 2013
The Mills lab found that the major tumor suppressor Chd5 binds to histone H3, offering insight into how this protein regulates a diverse set of cancers.
Alea Mills explains mouse modeling at the Secret Science Club
April 3, 2012
LabDish blog A rapt audience of more than 450 New Yorkers gathered at the Secret Science Club in Brooklyn on one unseasonably balmy night in mid-March to listen to tales of gene hunting expeditions by CSHL Professor Alea Mills. She is an expert in chromosome engineering, a technique for developing mouse models of human disease...
CSHL team finds evidence for the genetic basis of autism
October 3, 2011
Models of autism show that gene copy number controls brain structure and behavior Cold Spring Harbor, NY — Scientists at Cold Spring Harbor Laboratory (CSHL) have discovered that one of the most common genetic alterations in autism—deletion of a 27-gene cluster on chromosome 16—causes autism-like features. By generating mouse models of autism using a technique...
Study finds a stem cell origin of skin cancer and the genetic lesions that promote its malignancy
February 4, 2011
Findings reveal a new role for p63—a sister gene of the master tumor suppressor p53—in cancer and stem cell biology Cold Spring Harbor, NY — A constellation of different stem cell populations within our skin help it to cope with normal wear and tear. By constantly proliferating, the stem cells allow skin to replenish itself,...
CSHL study shows that malignant tumors can be shut down after all
November 9, 2009
Aggressive tumors lacking p53 protein stop dead in their tracks when p53’s sister protein—TAp63—steps in Cold Spring Harbor, NY — Oncologists have had their hands tied because more than half of all human cancers have mutations that disable a protein called p53. As a critical anti-cancer watchdog, p53 masterminds several cancer-fighting operations within cells. When...
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 atCSHL Institutional Repository