Research & Publications
We employ a comprehensive approach human genetic disorders, attempting to understand their clinical presenations by studying their genetics and pathobiology. Using genetic tools, we have identified new genetic causes of inherited disorders and we are actively studying how these genes function in health and disease.
Extensive Research Description
Genetics has informed our understanding of normal skin development and differentiation, largely due to the fact that mutations affecting the skin result in easily observed phenotypes. Genetic investigation has permitted us to identify a priori pathways previously unrecognized to be relevant to skin biology. These insights have been relevant to diagnosis, disease prevention, and development of novel therapeutics.
We have three ongoing projects in the lab:
1. Identification of novel genetic causes of inherited skin disorders including ichthyosis, inflammatory disorders and alopecia. We have developed one of the largest registries of kindreds with ichthyosis and have identified over 10 new genetic cause of this group of disorders – we employ cell, murine, and engineered tissue models to understand that biological basis of disease and the role of novel genes in disease pathobiology.
2. Identification of novel genetic causes of mosaic skin disorders including childhood malformations, vascular tumors, and linear presentations of inflammatory disorders. Mosaic disorders are the result of embryonic somatic mutation, with timing of mutation determining the extent of disease. Among other discoveries, we have systematically dissected pathways leading to development of aggressive infantile vascular tumors, identified novel causes of acne pathogenesis and hair follicle differentiation, and have identified Ras as a regulator of phosphate homeostasis. A new project is focused on linear manifestation of common inflammatory disorders such as lupus, psoriasis, and lichen planus with the expectation that investigation will identify novel pathways in cutaneous innate immunity.
3. Elucidation of mechanisms of revertant mosaicism in ichthyosis with confetti to enable therapeutic recombination in the skin. We have found that specific mutations in KRT1 and KRT10 cause ichthyosis with confetti which undergoes spontaneous self-correction via revertant mosaicism, resulting in hundreds to thousands of patches of normal skin. All spots arise from mitotic recombination, and have found that keratin mutations directly influence DNA damage and repair and that cellular competition favors reversion. We are employing forward genetics to identify the pathways relevant to recombination and competition.
Cell Biology; Genetics; Genetics, Medical; Ichthyosis; Mosaicism; Skin Diseases; Human Genome Project; Skin and Connective Tissue Diseases; Human Genetics
Public Health Interests
Genetics, Genomics, Epigenetics; Child/Adolescent Health