2000-2001 NAAF Research Grant Awardees

1. Amos Gilhar, M.D., The Technion-Israel Institute of Technology, Haifa, Israel, and Richard S. Kalish, M.D., Ph.D., State University of New York at Stony Brook, will further their investigation into the “Molecular Basis of Alopecia Areata.” They have demonstrated, with prior NAAF funding, that the hair loss in alopecia areata is due to white blood cell (T-lymphocytes) attacks on hair follicles. The next goal is to find the specific protein that activates these white blood cells to launch the attack. Preliminary data generated by these investigators implicates pigment cell (melanocyte) proteins that turn on the white blood cells and cause alopecia areata. The purpose of this project is to obtain data from a larger number of patients on which pigment proteins turn on their T-lymphocytes. This information is needed for further development of specific immunotherapies for alopecia areata.

2. Bruce A. Morgan, Ph.D., Massachusetts General Hospital in Charlestown, will conduct a study on “Signaling to the Dermal Papilla.” Hair growth depends on communication between cells in different layers of the hair follicle. Cells at the base of the hair follicle, which compose the dermal papilla, induce cells in the overlying layer to form the hair shaft. The inductive activity of the dermal papilla is in turn maintained by signals from cells at the base of the hair shaft while the hair is actively growing, but is lost when the hair ceases to grow during the quiescent phase of the hair cycle. Dr. Morgan will identify the signals that activate dermal papilla cells so that those cells may instruct a new hair shaft to grow. A better knowledge of the signals used to communicate between cells in the hair follicle may be applied to reversing the hair loss caused by alopecia areata.

3. John P. Sundberg, Ph.D., The Jackson Laboratory, Bar Harbor, ME, will receive funds to support the “Distribution of a Mouse Model for Alopecia Areata.” Alopecia areata is an autoimmune disease directed against the growing stage of hair follicles. Dr. Sundberg and others have developed a mouse model that closely resembles human alopecia areata called the “NAAF Mouse”, since NAAF supported its initial development. The mouse mechanism appears to be similar, if not identical, to the human disease and preliminary studies have indicated that the mice respond to the same treatments as people do. The model is dependent upon grafting skin from affected mice onto normal mice that can accept the grafts. Due to the fact that this is a labor-intensive procedure, support is necessary to produce and distribute these mice to investigators around the world, thereby expediting research on ways to treat alopecia areata.

4. Rachid Tazi-Ahnini, Ph.D., and Michael J. Cork, Ph.D., both at the Royal Hallamshire Hospital in Sheffield, England, will conduct a study on the “Role of the Autoimmune Regulator (AIRE) Gene in Alopecia Areata.” About one quarter of people with alopecia areata have another family member affected and it is known that several genes are involved in causing the condition. Drs. Tazi-Ahnini and Cork have recently found specific evidence that genes located on Chromosome 21 are involved in alopecia areata. This fact is underscored by knowledge that alopecia areata is commoner than usual with Down syndrome, in which there is a major abnormality on Chromosome 21. Alopecia areata is commonest of all in people with a rare disease called autoimmune polyendocrinopathy (APECED) and the gene responsible (AIRE) is now known to also be located on chromosome 21. The investigators plan to test AIRE in people with alopecia areata and their families. Confirming AIRE abnormalities should provide opportunities to design new treatments that attack the root cause of alopecia rather than just suppressing it.

5. Sarah E. Millar, Ph.D., University of Pennsylvania, Philadelphia, will continue her study on “WNT Signaling in Hair Follicle Formation and Hair Growth.” Hair follicle formation in embryos and hair growth in the adult are processes that involve communication between hair follicle cells of different types. Failure of this dialog between cells can result in a lack of hair growth or hair loss. Cells communicate by sending and receiving protein messengers. Dr. Millar’s laboratory discovered that increased levels in hair follicles of the WNT3 messenger, a member of the WNT family of signaling proteins, cause fragile hair and hair loss. Dr. Millar has now found that other WNT proteins are present in developing and mature hair follicles. She proposes to study their functions in the control of hair formation and growth. These experiments will provide important information about the molecular mechanisms underlying normal hair growth and hair loss disease. Ultimately, they may facilitate the development of novel therapies for hair loss disease.

6. Maria Hordinsky, M.D. and Marna Ericson, Ph.D., both at the University of Minnesota in Minneapolis, will conduct a study on “Phenotype and Cytokine Production Characteristics of T Cells from Alopecia Areata Scalp Skin Before and After Aldara 5% Cream Using Flow Cytometry.” Alopecia areata occurs as the result of an inappropriate response of the body’s immune system to as yet unknown substances in or around the hair follicle. Prior research has demonstrated that T lymphocytes (a special category of white blood cells) are responsible for the assault on the hair follicle in the immune attack. In this study, the investigators will examine the efficacy of Aldara Cream 5%, a known immunomodulatory agent. Research will determine how Aldara Cream affects the hair follicle and the inflammation present in the skin of patients with alopecia areata. The T lymphocytes will be extracted and analyzed individually in order to determine the type and quantity of inflammatory products they produce. This type of information will provide data about the behavior of these cells in mediating the hair loss associated with alopecia areata, as well as how this behavior may be effected by Aldara Cream 5% treatment.

7. Hung Tseng, Ph.D., University of Pennsylvania in Philadelphia, will conduct a study entitled “Does Gli 1 Regulate Basonuclin Expression During Hair Follicle Development?” Understanding the molecular mechanisms that control hair follicle development is an essential part in devising new therapeutics for treating alopecia areata. Hair follicles arise from embryonic epidermis and this process requires complex communications between cells. One of the cellular signals is conducted by the Sonic hedgehog pathway, which induces expression of genes required for hair follicle development. In this study, Dr. Tseng aims to demonstrate that the signal of the Sonic hedgehog pathway induces the expression of basonuclin, a transcriptional regulator that may play an important role in follicular development. This knowledge will help us understand how cellular signaling and responses are achieved during embryonic hair follicle formation, important information that may one day allow the re-creation of hair follicles in adult skin.

NOTE:In addition to these seven grants, NAAF has agreed to support the ongoing work of Angela Christiano, Ph.D., Columbia University, New York City, and Madeleine Duvic, M.D., MD Anderson Cancer Center, Houston, who are investigating the genetic basis of alopecia areata and are developing an alopecia areata patient registry and database. The nature of that support will be determined after the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) makes its grant award announcements this fall. NIAMS recently announced that it will fund five new patient research registries, and a team headed by principal investigator Dr. Duvic has submitted a proposal focused on alopecia areata.