The Rockefeller University
Election Year: 1996
Primary Section: 22, Cellular and Developmental Biology
Secondary Section: 41, Medical Genetics, Hematology, and Oncology
Membership Type: Member
My laboratory studies the mechanisms underlying differentiation and development in mammalian ectoderm and their relation to genetic diseases of the skin and nervous system. Epidermal cells and neurons are the only cells that devote most of their time to making an extensive cytoskeletal network of intermediate filaments (IFs). Using tissue culture and transgenic/knockout mice as model systems, we employed biochemistry, genetics, and cell and molecular biology to characterize the program of keratin IF expression in epidermis and to provide insights into the macromolecular process of IF assembly. Beginning with an interest in keratin proteins, we worked our way up to elucidating the bases of a group of human keratin disorders. More recently, we have focused on how cytoskeletal filaments form an architecture in cells. This has led us to a novel gene that in epidermal cells, makes a protein that connects keratin networks to hemidesmosomes and in axons, makes a protein that interconnects the actin and neurofilament cytoskeletons. Mice missing this protein are defective in wound healing and display gross neurologic degeneration. In the future such studies will hopefully lead us to the genetic bases of human neurological disorders, as well as provide additional insights into human genetic skin diseases.