Moye-Rowley Laboratory Research Activities
Our laboratory is interested in the molecular basis underlying the response of eukaryotic cells to environmental stress. We are using the yeast Saccharomyces cerevisiae as a model organism for the cell and molecular biological response of eukaryotic cells to two different types of environmental challenges, cytotoxic drugs and oxidative stress. We have found that the cellular response to each of these stress regimens is modulated by the action of transcriptional regulatory proteins and often involves the expression of ATP binding cassette (ABC) transporter proteins. A brief description of each research area is presented below. More detail can be found by clicking on the link of interest and publications on these areas are listed here.
Pleiotropic Drug Resistance
A major problem in the
chemotherapy of cancer is the appearance of drug resistant tumor cells.
Often these drug resistant tumors exhibit broad range tolerance to
several structurally unrelated cytotoxic drugs. This ability to
tolerate a variety of different drugs is referred to as multidrug
resistance. One of the best understood mechanisms behind the acquistion
of multidrug resistance involves the overproduction of an ABC
transporter protein designated MDR1. This membrane protein acts as an
ATP-dependent drug pump and prevents the accumulation of toxic levels
of target compounds. Saccharomyces cerevisiae
exhibits loci that can be altered to give rise to multidrug resistance
(referred to in this organism as pleiotropic drug resistance). We
are also expanding our studies into the human pathogenic fungus Candida glabrata which can acquire
a multidrug resistance phenotype that is highly related to that seen in
S. cerevisiae. Along
with analyses of the transcriptional regulatory systems involved in
control of fungal multidrug resistance, we are interested in the
function and activity of proteins encoded by target genes. We have isolated an ABC
transporter-encoding gene (YOR1) from S.
cerevisiae that is regulated by the PDR system and
are analyzing the trafficking of this protein through the secretory
pathway. Our goal is to use Yor1p trafficking as a model for the
delivery of ABC
transporters to their final destination in eukaryotic
cells. This work is described here.
Membrane Lipid Composition
Oxidative Stress Resistance
An inescapable challenge posed to all cells growing under aerobic conditions is the production of reactive oxygen species that can damage intracellular components. To deal with this problem, cells elaborate a variety of different proteins and small molecules that are directed towards maintaining normal intracellular redox balance. In S. cerevisiae, transcriptional control of many of these oxidative stress resistance components is provided by the transcription factor Yap1p. We are studying how Yap1p is activated upon oxidative stress challenge as well as the downstream target genes that are important in maintenance of redox balance.
Comments or Problems?
Contact the "Webmaster.
Details about our site are available here.
© Copyright 1996 Scott Moye-Rowley. All
Last updated November 10, 2009.