test

Leonard M Milstone MD

Professor Emeritus of and Senior Research Scientist in and Research Scientist in Dermatology

Research Interests

Keratinocytes; Keratins; Ichthyosis; Iron; Oligonucleotide; Proteoglycans; Vitamin A; Gene Therapy; Genodermatoses

Current Projects

Leonard 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.

Research Summary

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.


Selected Publications

  • Milstone LM, Miller K, Haberman M, Dickens J. Incidence of moderate to severe ichthyosis in the United States. Arch Dermatol, 148:1080-1081, 2012
  • Rogers FA, Hu R-H, Milstone LM. Local delivery of gene-modifying triplex-forming molecules to epidermis. J Invest Dermatol, in press
  • Milstone LM, Hu R-H, Dziura JD, Zhou J. Impact of epidermal desquamation on tissue stores of iron. J Dermatol Sci, 67: 9-13, 2012
  • Choate KA, Yu L, Zhou J, Choi M, Elias PM, Farhi A, Nelson-Williams C, Crumrine D, Williams ML, Nopper AJ, Bree A, Milstone LM, Lifton RP. Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science, published online 26 August 2010; 10.1126/science.1192280
  • Leachman SA, Hickerson RP, Schwartz ME, Bullough EE, Hutcherson SL, Boucher KM, Hansen CD, Eliason MJ, Srivatsa GS, Kornbrust DJ, Smith FJD, McLean WHI, Milstone LM, Kaspar RL. First-in human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder. Molec Therapy 18:442-446, 2010
  • Adams BD, Lazova R, Andrews NC, Milstone LM. Iron in skin of mice with three etiologies of systemic iron overload. J Invest Dermatol, 125:1200-1205, 2005
  • Leachman SA, Insogna KL, Katz L, Ellison A, Milstone LM. Bone densities in patients receiving isotretinoin for cystic acne. Arch Dermatol 135:961-966, 1999
  • Milstone LM, Hough-Monroe L, Kugelman LC, Bender JR, Haggerty JG. Epican, a heparan/ chondroitin sulfate proteoglycan form of CD44, mediates cell-cell adhesion. J Cell Sci 107: 3183-3190, 1994
  • Petty EM, Spiesel SZ, Seashore M, Braverman IM, Smith LT, Byers PH, Milstone LM. Dermatosparaxis in humans: a case report and description of the newly recognized phenotype. Arch Dermatol 129:1310-1315, 1993
  • Kugelman LC, Ganguly S, Haggerty JG, Weissman SM, Milstone LM. The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44. J Invest Dermatol 99:887-891, 1992

Read more...

Edit Profile