Columbia University Medical Center

New Hair Loss Gene Identified By Columbia Led Research Team

Mutation in Gene Leads to a Type of Thin Hair,
also Seen in Male Pattern Baldness

NEW YORK (April 14, 2010) – A team of investigators from Columbia, Rockefeller and Stanford Universities has identified a new gene involved in hair growth, as reported in a paper in the April 15 issue of Nature. This discovery may affect future research and treatments for male pattern baldness and other forms of hair loss.

The researchers found that the gene, called APCDD1, which causes a progressive form of hair loss beginning in childhood (known as hereditary hypotrichosis simplex). The disease is caused by a phenomenon called hair follicle miniaturization – the same key feature of male pattern baldness. When hair follicles go through this miniaturization process, they shrink or narrow, causing the thick hair on the head to be replaced by thin, fine hair, known as “peach fuzz.”

“The identification of this gene underlying hereditary hypotrichosis simplex has afforded us an opportunity to gain insight into the process of hair follicle miniaturization, which is most commonly observed in male pattern hair loss or androgenetic alopecia,” said Angela M. Christiano, Ph.D., professor of dermatology and genetics & development at Columbia University Medical Center, and lead author of the study. “It is important to note that while these two conditions share the same physiologic process, the gene we discovered for hereditary hypotrichosis does not explain the complex process of male pattern baldness.”

The team made their discovery by analyzing genetic data from a few families from Pakistan and Italy with hereditary hypotrichosis simplex. They found a common mutation in the APCDD1 gene, which is located in a specific region onchromosome 18 that has been shown in previous studies to be implicated in other forms of hair loss, including androgenetic alopecia and alopecia areata, hinting at a broader role in hair follicle biology.

Importantly, the researchers found that APCDD1 inhibits a signaling pathway that has long been shown to control hair growth in mouse models, but has not been extensively linked to human hair growth. Laboratory researchers have targeted this pathway, known as the Wnt signaling pathway, to turn on or off hair growth in mice, but, until now, the pathway did not appear to be involved in human hair loss. This finding is significant because it provides evidence that hair growth patterns in humans and in mice are more similar than previously believed.

“We have at last made a connection between Wnt signaling and human hair disease that is highly significant,” said Dr. Christiano. “We have years of beautiful data in our field about hair growth in mice, but this is the first inroad into showing that the same pathway is critical in human hair growth. This is the first mutation in a Wnt inhibitor that deregulates the pathway in a human hair disease.”

“Furthermore, these findings suggest that manipulating the Wnt pathway may have an effect on hair follicle growth – for the first time, in humans,” said Dr. Christiano. “And unlike commonly available treatments for hair loss that involve blocking hormonal pathways, treatments involving the Wnt pathway would be non-hormonal, which may enable many more people suffering from hair loss to receive such therapies.”

Dr. Christiano and her team are now working to understand the complex genetic causes of other forms of hair loss including alopecia areata, with the hope of eventually developing new, effective treatments for these conditions.

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Authors of the paper are: Yutaka Shimomura 1*, Dritan Agalliu 2;*, Alin Vonica 3*, Victor Luria 1, 6 *, Muhammad Wajid 1, Alessandra Baumer 4 , Serena Belli 5, Lynn Petukhova 1, Albert Schinzel 4, Ali H. Brivanlou 3, Ben A. Barres 2† and Angela M. Christiano 1,6†

Affiliations:

1Departments of Dermatology and 6Genetics & Development, Columbia University, New York, NY, USA; 2Department of Neurobiology, Stanford University, Stanford, CA, USA; 3The Laboratory of Vertebrate Embryology, The Rockefeller University, New York, NY, USA; 4Institute of Medical Genetics, University of Zurich, Zurich, Switzerland; 5Struttura Semplice Genetica Medica APSS, Trento, Italy.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the most comprehensive medical research enterprise in New York City and State and one of the largest in the United States. Columbia University Medical Center is affiliated with NewYork-Presbyterian Hospital, the nation’s largest not-for-profit hospital provider. For more information, please visit www.cumc.columbia.edu.

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