1999-2000 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 investigate “The Molecular Basis of Alopecia Areata”. They have demonstrated, with previous NAAF funding, that alopecia areata lesions can be induced by T lymphocytes that appear to recognize and attack hair follicles. The next goal is to find the protein that activates these T lymphocytes to attack hair follicles. There is evidence that the pigment cells (melanocytes) in the hair follicle are the target of the T lymphocytes. The purpose of this project is to first confirm that pigment cell proteins can activate T lymphocytes that are involved in alopecia areata, and then to find which pigment cell proteins are involved in inducing alopecia areata. Identification of the protein (antigen) that induces alopecia areata would be a major breakthrough, as it would make possible the development of specific immunotherapy for alopecia areata.

2. George Cotsarelis, M.D., University of Pennsylvania in Philadelphia, will continue his study on “Gene Therapy for Alopecia Areata”. This research should bring us one step closer to using gene therapy for the treatment of alopecia areata. The long-term goals of this research are to better understand hair follicle stem cells, and to develop methods for introducing genes into human hair follicle cells in order to treat alopecia areata and other skin disorders using gene therapy. Dr. Cotsarelis' research has identified a protein (K15) found in hair follicle stem cells, and now he proposes to isolate the portion of the K15 gene (called the “promoter”) that controls K15 expression in those cells. Once accomplished, this will provide a powerful tool for manipulating hair follicle stem cells. His studies will continue introducing foreign genes into both mouse and human hair follicles using topical liposome-mediated delivery. In this research plan, he will also use viral vectors for delivering genes to the hair follicle.

3. Madeleine Duvic, M.D., and Ana A. Oliveria Hoff, M.D., both at the MD Anderson Cancer Center in Houston, will investigate “The Role of Calcitonin Gene Related Protein (CGRP) in the Pathogenesis of Alopecia Areata”. It has been observed that CGRP, a neuropeptide, suppresses immune reactions and alopecia areata patients have a decreased serum level of CGRP. Mice that lack CGRP develop an inflammatory alopecia that resembles alopecia areata. The hypothesis is that loss of CGRP in hair-bearing skin may allow a targeted immune response to hair follicles resulting in alopecia areata. The availability of a mouse model that lacks CGRP allows a study of the role of CGRP in alopecia areata.

4. Vladimir A. Botchkarev, M.D., Ph.D., Department of Dermatology, Boston University Medical School, will investigate “A Role For Neurotrophins and their Receptors in the Pathogenesis of Alopecia Areata”. This proposal focuses on the hypothesis that neurotrophins and their receptors play a role in the pathogenesis of alopecia areata. A detailed analysis of the distribution of neurotrophins and their receptors in alopecia areata will be made, and this raises the possibility for use of neurotrophin receptor antagonists for the treatment of alopecia areata and related hair growth disorders.

5. Yan Chun Li, Ph.D., University of Chicago, will study “Ligand-Independent Action of the Vitamin D Receptor in the Regulation of Hair Cycle”. It is observed that vitamin D receptor (VDR) defect, but not vitamin D deficiency, results in complete loss of hair. The hypothesis is that the regulation of hair growth by the vitamin D receptor is independent of vitamin D or its most active metabolite, 1,25-dihydroxy vitamin D3. This study proposes to explain these seemingly contradictory observations by studying VDR knockout mice.

6. Sarah E. Millar, Ph.D., University of Pennsylvania, Philadelphia, will investigate “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 discovered that increased levels in hair follicles of the WNT3 messenger, a member of the WNT family of signaling proteins, causes the hair to be fragile and results in hair loss. She proposes to determine which other WNT proteins are present in developing and mature hair follicles and 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, and ultimately may facilitate the development of novel therapies for hair loss.

7. Gabriele Richard, M.D., Thomas Jefferson University, Philadelphia, Sheri Bale, Ph.D., NIH/NIAMS Genetic Studies Section, Bethesda, Maryland, and John DiGiovanna, M.D., Brown University, Rhode Island, will conduct “Clinical and Genetic Studies of Netherton Syndrome, a Congenital Recessive Ichthyosis Associated with Hair Shaft Anomalies and Immune Deficiency”. Netherton syndrome is a rare inherited disorder of skin and hair associated with immunologic problems. It is characterized by generalized redness and scaling of the skin, which may develop into scaling plaques. Patients have a characteristic hair shaft ball and socket defect resembling bamboo joints. The affected hair is thin, sparse, and breaks easily at the bamboo joints and leads to diffuse hair thinning. Netherton syndrome may also include elevated immunoglobulin levels, allergies, recurrent infections, and other manifestations. The goal is to study the clinical spectrum of the syndrome, define the chromosomal location of the responsible genes, and ultimately, identify the underlying genetic defects responsible for Netherton syndrome. This knowledge will discover new mechanisms leading to hair shaft abnormalities, and enhance the understanding of normal structure, function and interconnection of skin, hair and the immune system.

8. Marty Sawaya, M.D., Ph.D., University of Miami School of Medicine, and Robert W. Keane, Ph.D., University of Miami, will study “The Regulation of Apoptosis by Caspases in Alopecia Areata”. Alopecia areata is associated with an inflammatory reaction at the lesion site and dysregulation of programmed cell death, but the mechanisms governing the disease process are still unknown. Experimental and clinical evidence indicates that apoptosis, a form of programmed cell death, is an important process in normal cell turnover for maintenance of skin and hair in adults. The overall goal of this study is to define and characterize the specific proteins involved in cell interaction in the normal dynamic cycles of hair growth and those induced in alopecia areata. A secondary goal is to determine immune involvement in the disease process. These studies may provide new therapeutic strategies to treat alopecia areata.

9. Wasim Ahmad, Ph.D., and Angela M. Christiano, Ph.D., both of the Department of Dermatology at Columbia University in New York, will conduct “Genetic Studies in Inherited Alopecias”. In previous NAAF-funded research, they were successful in establishing genetic linkage and identification of a mutation in the human hairless gene in a rare non-inflammatory form of generalized hair loss. In this study, they propose genetic linkage analysis using DNA pooling and homozygosity mapping in a large Pakistani family with an inherited form of inflammatory alopecia, followed by positional cloning of the underlying genes. Positional cloning of the genes underlying the alopecia in this family and in previously studied families, will advance our understanding of genetic control of the hair cycle, and add to the discovery of genes responsible for the pathogenesis of inherited hair loss.