Myung Hee Park, Ph.D. Chief
Mission
The goal of this Unit is the understanding of molecular structure/biological function relationships. Its major emphasis has been centered around enzymes involved in a unique posttranslational modification reaction resulting in the formation of the unusual amino acid hypusine in a single cellular protein, eukaryotic translation initiation factor 5A (eIF5A). The essential role of the hypusine modification in the activity of eIF5A and in eukaryotic cell proliferation has now been demonstrated in studies in yeast and mammalian cells, and the biosynthetic pathway of hypusine which involves two enzymes, deoxyhypusine synthase and deoxyhypusine hydroxylase, has been revealed through the UnitÕs efforts. Potent inhibitors of one of these enzymes, deoxyhypusine synthase, have been developed and shown to exert strong antiproliferative effects on normal and cancer cells. These findings have furthered the knowledge of the role of hypusine modification and offered a potential mechanism for control of normal and aberrant cell growth. In addition, this Unit has recently established a research program on human oral keratinocytes as a part of the head and neck cancer program of OPCB. Its goal is to understand the normal control mechanisms underlying the regulation of proliferation, differentiation and apoptosis of human oral keratinocytes and to understand the multistep genotypic and phenotypic changes associated with oral carcinogenesis.
Personnel