The research focus of our laboratory has been upon the initiation of stress-responsive and apoptotic programs in eukaryotic cells. The mechanisms through which cells adapt and respond to external and internal stresses are diverse and fascinating. Severe stress can activate a cellular suicide program known as apoptosis (programmed cell death). Entrance of a cell into apoptosis initiates a cascade of proteolytic events, culminating in the destruction of cellular macromolecules, membranes, and organelles by cytosolic and nuclear enzymes. Using mouse cells in tissue culture, we are currently characterizing the activation of cell death that results from abnormalities in the endoplasmic reticulum (ER). The loss of glycosylation activity during protein synthesis in the ER results in a dramatic apoptotic phenotype. Also of interest to our research group are the downstream targets of stress-activated signal transduction cascades (the genes being activated in response to cellular stress). We employ the budding yeast, Saccharomyces cerevisiae, as a model system for stress-activated signal transduction. We have recently cloned and are currently characterizing a set of genes that are activated by the HOG (high osmolarity glycerol response) signal transduction cascade following osmotic stress.

Publications:

Brewster JL, Linseman DA, Bouchard RJ, Loucks FA, Precht TA, Esch EA, and KA Heidenreich (2006), Endoplasmic reticulum stress and trophic factor withdrawal activate distinct signaling cascades that induce glycogen synthase kinase-3beta and a caspase-9-dependent apoptosis in cerebellar granule neurons, Molecular and Cellular Neuroscience, 32 (3): 242-53.

Niederer KE, Morrow DK, Gettings JL, Irick M, Krawiecki A, and JL Brewster (2005), Cypermethrin blocks a mitochondria-dependent apoptotic signal initiated by deficient N-linked glycosylation within the endoplasmic reticulum, Cellular Signalling,17(2):177-186.

Brewster JL, Beason KB, Eckdahl TT, and IM Evans (2004), The Microarray Revolution: Perspectives from Educators, Biochemistry and Molecular Biology Education, 32(4):217-227.

Runner, VM, and JL Brewster (2003), A genetic screen for yeast genes induced by sustained osmotic stress, Yeast , 20:913-920.

Baggato B, Brewster JL, Burggren W, and L Hester (1st Ed. 2002, 2nd Ed. 2004), Biological Science: Study Guide, Prentice Hall Publishers, New York.

Brewster JL, Martin SL, Toms J, Goss D, Wang K, Zachrone K, Davis A., Carlson G, Hood L, and JD Coffin (2000), Deletion of Dad1 in mice induces an apoptosis-associated embryonic death, Genesis: The Journal of Genetics and Development, 26:271-278.

Brewster, JL, O'Moore J, and WR Crain (1999), Use of enhanced differential display to identify gene expression differences in male and female mouse genital ridges, A comparative methods approach to the study of oocytes and embryos, Oxford University Press, pp. 157-169.

Schuller C, Brewster JL, Alexander M, Gustin MC, and H Ruis (1994), The HOG pathway controls osmotic regulation of transcription via the stress response element (STRE) of the Saccharomyces cerevisiae CTT1 gene, The EMBO Journal 13:4382-4389.

Brewster JL, and MC Gustin (1994), Positioning of cell growth and division after osmotic stress requires a MAP kinase pathway, Yeast 10:425-439.

Brewster JL, de Valoir T, Dwyer N Winter E, and MC Gustin (1993), An osmosensing signal transduction pathway in yeast, Science 259:1760-1763.

External Research Funding Sources:

National Institutes of Health (2008-11) Academic Research Enhancement Award (R15 GM065139-02A1), “Analysis of apoptotic signaling induced by the endoplasmic reticulum” – Principal Investigator.

National Science Foundation (2005-10) – Research Experience for Undergraduates (REU site grant), “Undergraduate Research in Biology: A Way of Discovery”, Co-Principal Investigator.

National Institutes of Health (2002-06) Academic Research Enhancement Award (R15 GM065139-01), “Characterization of OST-based activation of apoptosis” – Principal Investigator.

National Science Foundation (2003) – Research Experience for Undergraduates (REU site grant), “Undergraduate Research in Biology: A Way of Discovery”, Co-Principal Investigator.

National Science Foundation (2002) – Major Research Inst. Grant (MRI/RUI - 0215516), “Acquisition of a Real-Time Quantitative PCR Instrument for Undergraduate Research and Teaching” – Co-Principal Investigator.

National Science Foundation (2000-03)-Research Experience for Undergraduates (REU) site grant (DBI 9987543) "Undergraduate Research in Biology: A Way of Discovery"; Co-principal investigator.

National Institutes of Health (1995), Postdoctoral Training Fellowship, “Sex specific gene expression in early mouse embryos” - (approved by NIH, but was not activated due to associateship offer from Stowers Institute).

National Institutes of Health (1991-93), Predoctoral Training Fellowship.