The eukaryotic initiation factor 5A is the only protein known to contain a hypusine residue, an unusual amino acid formed by the action of deoxyhypusine synthase and deoxyhypusine hydroxylase using spermidine as the substrate. Although genes encoding eIF-5A and deoxyhypusine synthase are essential for cell survival and proliferation, the function of eIF-5A is unknown. We have generated almost all the molecular tools to study the biochemistry and function of eIF-5A and the significance of its hypusine formation. The biological systems used are mammalian cells, yeast, and C.elegans.
Cancer Biology Project:
There are three focuses: (i) Systematic screening of food chemicals and nutraceuticals isolated from plants that are anti-proliferative, anti-inflammatory, or pro-apoptotic. We are particularly interested in nutraceuticals that may modulate or inhibit important or disease-related genes such as NF-kB, p53, ornithine decarboxylase, and cyclooxygenase 2 (Cox-2), either at transcriptional or translational level. Novel methodologies, including microarray, are being developed to perform these screenings. (ii) Design and synthesis of compounds targeting at polyamine network, including hypusine formation. High polyamine content has known to be associated with many cancer types, (iii) Design and synthesis natural product-based compounds that possess clear and enhanced differential growth inhibitory effect against tumor cells in vitro and in vivo.
Cellular Aging Project:
The hallmark of cell aging is the loss of dividing potential in normal cells during senescence. A global change of expressions of G1/S genes in human diploid cells during aging process, which ensures limited lifespan of normal cells. Our current focuses are: (i) the role of NF-Y and E2F on this global change and (ii) screening for small molecules that can modulate the lifespan of cells.
Osmosis Stress Project
Similar to heat stress, osmotic stress activates HSF1. Unexpectedly, both hypo- and hyper-osmotic stress produce similar activation. We are studying the mechanism and physiological significance of this intriguing phenomenon.