A5025458943- DNA Repair Mechanisms
- Fungal and yeast genetics research
- Carcinogens and Genotoxicity Assessment
- CRISPR and Genetic Engineering
- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Cancer-related Molecular Pathways
- Gene expression and cancer classification
- Genetics, Aging, and Longevity in Model Organisms
- Effects of Radiation Exposure
- Photosynthetic Processes and Mechanisms
- Mitochondrial Function and Pathology
- Gene Regulatory Network Analysis
- Plant Genetic and Mutation Studies
- PARP inhibition in cancer therapy
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Vectors
- MicroRNA in disease regulation
- PI3K/AKT/mTOR signaling in cancer
- Nail Diseases and Treatments
- Cardiovascular Disease and Adiposity
- Microtubule and mitosis dynamics
- Mosquito-borne diseases and control
- RNA and protein synthesis mechanisms
- ATP Synthase and ATPases Research
Colorado State University
2011-2023
Yale University
1994-2023
University of New Mexico
2003-2014
New Mexico Cancer Center
2012
University of California, San Francisco
2011
The University of Sydney
2003-2010
Royal Children's Hospital
2010
Resonance Health (Australia)
2003
Lawrence Berkeley National Laboratory
2002
Quiescence is the most common and, arguably, poorly understood cell cycle state. This in part because pure populations of quiescent cells are typically difficult to isolate. We report isolation and characterization nonquiescent from stationary-phase (SP) yeast cultures by density-gradient centrifugation. Quiescent dense, unbudded daughter formed after glucose exhaustion. They synchronously reenter mitotic cycle, suggesting that they a G0 Nonquiescent less heterogeneous, composed...
Cells in glucose-limited Saccharomyces cerevisiae cultures differentiate into quiescent (Q) and nonquiescent (NQ) fractions before entering stationary phase. To understand this differentiation, Q NQ cells from 101 deletion-mutant strains were tested for viability reproductive capacity. Eleven mutants that affected one or both phenotypes identified. exhibit a high level of petite colonies, nine affecting phenotype Microarray analysis revealed >1300 mRNAs distinguished fractions. cell-specific...
Extracellular vesicles (EVs) are biomarkers and modifiers of human disease. EVs secreted by insulin-responsive tissues like skeletal muscle (SkM) white adipose tissue (WAT) contribute to metabolic health disease but the relative abundance from these has not been directly examined. Human Protein Atlas data measuring EV secretion in mouse SkM WAT using an ex vivo explant model confirmed that secretes more than WAT. Differences between were due contraction may be explained differences capacity....
DNA-dependent protein kinase (DNA-PK), composed of Ku70, Ku80, and the catalytic subunit (DNA-PKcs), is involved in repairing double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ). Certain proteins NHEJ are also DSB repair homologous recombination (HR). To test effects DNA-PKcs on DSB-induced HR, we integrated neo direct repeat HR substrates carrying I -Sce recognition sequence into DNA-PKcs-defective Chinese hamster ovary (V3) cells. The defect was complemented with a human cDNA....
Most cells on earth exist in a quiescent state. In yeast, quiescence is induced by carbon starvation, and exit occurs when source becomes available. To understand how survive in, from this state, mRNA abundance was examined using oligonucleotide-based microarrays quantitative reverse transcription-polymerase chain reaction. Cells stationary-phase cultures exhibited coordinated response within 5-10 min of refeeding. Levels >1800 mRNAs increased dramatically (>or=64-fold), smaller group...
Modeling of gene expression data from time course experiments often involves the use linear models such as those obtained principal component analysis (PCA), independent (ICA), or other methods. Such methods do not generally yield factors with a clear biological interpretation. Moreover, implicit assumptions about measurement errors limit application these to log-transformed data, destroying structure in untransformed data.In this work, method for decomposition by multivariate curve...
As yeast cultures enter stationary phase in rich, glucose-based medium, differentiation of two major subpopulations cells, termed quiescent and nonquiescent, is observed. Differences mRNA abundance between exponentially growing stationary-phase nonquiescent cells are known, but little was known about protein these cells. To measure exponential cultures, the GFP-fusion library (4159 strains) examined during phases, using high-throughput flow cytometry (HyperCyt). Approximately 5% proteins...
We have obtained initial evidence supporting a new model for the human disease ataxia-telangiectasia (A-T), in which A-T and p53 genes play crucial roles signal transduction network that activates multiple cellular functions response to DNA damage. Three of model's predictions were tested. (1) Disrupting cell cycle checkpoints should increase spontaneous rates normal cells. In order interfere with G1/S checkpoint, we transfected line vectors expressing either dominant-negative p53ala143...
: Radiotherapy is an effective tool in the fight against cancer. It non-invasive and painless, with advanced tumor imaging beam control systems, radiation can be delivered to patients safely, generally minor or no adverse side effects, accounting for its increasing use a broad range of tumors. Tumors normal cells respond radiation-induced DNA damage by activating complex network signaling repair pathways that determine cell fate including survival, death, genome stability. response (DDR)...
Homologous recombinational repair (HRR) of DNA damage is critical for maintaining genome stability and tumor suppression. RAD51 BRCA2 colocalization in nuclear foci a hallmark HRR. has important roles focus formation HRR double-strand breaks (DSBs). We previously reported that BCCIPalpha interacts with BRCA2. show second isoform, BCCIPbeta, also this interaction occurs region shared by BCCIPbeta. further chromatin-bound colocalizes BCCIP most radiation-induced colocalize BCCIP. Reducing 90%...
Vacuolar ATPases (V-ATPases) are important for many cellular processes, as they regulate pH by pumping cytosolic protons into intracellular organelles. The cytoplasm is acidified when V-ATPase inhibited; thus we conducted a high-throughput screen of chemical library to search compounds that acidify the yeast cytosol in vivo using pHluorin-based flow cytometry. Two inhibitors, alexidine dihydrochloride (EC50 = 39 μm) and thonzonium bromide 69 μm), prevented ATP-dependent proton transport...
PURPOSE: To use magnetic resonance (MR) spectroscopy to characterize clinical isolates of Cryptococcus neoformans and a glioma cell line in culture experimental rats. MATERIALS AND METHODS: One- two-dimensional hydrogen 1 MR spectra were acquired from fungi cultured vitro (16 C neoformans, three Candida albicans, Aspergillus fumigatus, Saccharomyces cerevisiae) C6 line. Cerebral biopsy specimens obtained healthy rats animals with infections or gliomas (19 brains, 20 cryptococcomas, 19...
TOR (target of rapamycin) is a serine/threonine kinase, evolutionarily conserved from yeast to human, which functions as fundamental controller cell growth. The moderate clinical benefit rapamycin in mTOR-based therapy many cancers favors the development new inhibitors. Here we report high-throughput flow cytometry multiplexed screen using five GFP-tagged clones that represent readouts four branches TORC1 signaling pathway budding yeast. Each clone was differentially color-coded, and GFP...
Common cancer therapies employ chemicals or radiation that damage DNA. Cancer and normal cells respond to DNA by activating complex networks of sensor, signal transducer, effector proteins arrest cell cycle progression, repair damaged If is severe enough, the response (DDR) triggers programed death apoptosis other pathways. Caspase 3 a protease activated upon apoptosis, production prostaglandin E2 (PGE2), potent growth factor can enhance surviving leading accelerated tumor repopulation....
Melioidosis is caused by the facultative intracellular bacterium Burkholderia pseudomallei and potentially fatal. Despite a growing global burden high fatality rate, little known about disease. Recent studies demonstrate that cyclooxygenase-2 (COX-2) inhibition an effective post-exposure therapeutic for pulmonary melioidosis, which works inhibiting production of prostaglandin E2 (PGE2). This treatment, while effective, was conducted using experimental COX-2 inhibitor not approved human or...