Leonard M Milstone MD
Professor Emeritus of and Senior Research Scientist in and Research Scientist in Dermatology
Keratinocytes; Keratins; Ichthyosis; Iron; Oligonucleotide; Proteoglycans; Vitamin A; Gene Therapy; Genodermatoses
Current ProjectsLeonard Milstone follows one of the largest groups of patients with ichthyosis in the country. These patients have stimulated a number of collaborative studies on systemic effects of retinoids, on genotype-phenotype correlations and, currently, on revertant mosaicism.
His lab has an ongoing program to demonstrate that epidermal desquamation can be harnessed to remove systemic toxins from the body. Using iron as a model toxin, pharmacological and transgenic mouse models are tested for their ability to reduce the body burden of iron in mice with hemochromatosis. Appropriate interpretation of those studies has necessitated better characterization of iron homeostasis in keratincytes.
The lab also investigates methods to correct dominant negative gene defects in keratinocytes. One area of study is the use of triplex-forming oligonucleotides to induce mutations in a SupF reporter in mouse skin and in a keratin 6a-YFP reporter in tissue culture cells. The lab also participates in a large, international collaborative group, which has just completed a successful clinical pilot of siRNA to treat the mutant keratin disorder, pachyonychia congenita.
Leonard Milstone's laboratory studies have focused mainly on the structure and function of epidermal keratinocytes in tissue culture, in experimental animals and in patients who have ichthyosis. Past work includes: identification and characterization of keratins 4 and 13; discovery of epican, the CD44 proteoglycan characteristically found on stratified squamous epithelia; production of PTHrP by keratinocytes; seminal observations on interferon gamma.
Clinical studies have focused on effects that systemic retinoids have on bones of patients who have ichthyosis or acne, and on characterization of rare genodermatoses, such as dermatosparaxis and ichthyosis with confetti.