A5032658444- Virus-based gene therapy research
- Antifungal resistance and susceptibility
- Viral Infectious Diseases and Gene Expression in Insects
- Estrogen and related hormone effects
- Fungal Infections and Studies
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Monoclonal and Polyclonal Antibodies Research
- Viral gastroenteritis research and epidemiology
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Gene expression and cancer classification
- Probiotics and Fermented Foods
- Nuclear Receptors and Signaling
- Steroid Chemistry and Biochemistry
- Microbial Metabolic Engineering and Bioproduction
- Protein purification and stability
- Antimicrobial Peptides and Activities
- bioluminescence and chemiluminescence research
- Gut microbiota and health
- Transgenic Plants and Applications
National Research Council Canada
2006-2025
Biotechnology Research Institute
2003-2014
Université de Montréal
2006-2011
McGill University
1995-1999
Montreal Clinical Research Institute
1997
Centre National de la Recherche Scientifique
1989-1990
Inserm
1990
Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes
1989
University of Illinois Urbana-Champaign
1984-1986
Illinois College
1984-1986
Glycolysis is a metabolic pathway that central to the assimilation of carbon for either respiration or fermentation and therefore critical growth all organisms. Consequently, glycolytic transcriptional regulation important flexibility pathogens in their attempts colonize diverse niches. We investigated control carbohydrate metabolism human fungal pathogen Candida albicans identified two factors, Tye7p Gal4p, as key regulators glycolysis. When was inhibited oxygen limited, gal4tye7 C. strain...
Two important functions of glucocorticoids (Gc), namely, suppression immune system function and feedback repression the hypothalamo-pituitary-adrenal (HPA) axis, are mediated through gene transcription. Previous studies have indicated that this is exerted in part antagonism between glucocorticoid receptors (GR) AP-1 family transcription factors. However, mechanism could not account for pro-opiomelanocortin (POMC) gene, an regulator HPA axis. Our recent identification orphan nuclear receptor...
A number of expression systems have been developed where transgene can be regulated. They all specific characteristics making them more suitable for certain applications than others. Since some require the regulation several genes, there is a need variety independent yet compatible systems. We used regulatory mechanisms bacterial operons (cmt and cym) to regulate gene in mammalian cells using three different strategies. In repressor configuration, mediated by binding (CymR) operator site...
The level of estrogen receptor (ER) is a major factor regulating cell sensitivity to estrogen. We have determined the rates ER synthesis and turnover in MCF-7 breast cancer cells by incubating medium supplemented with 13C15N2H-amino acids (dense amino acids) monitoring shift from "old-light" (preexisting) "new-dense" (newly synthesized) receptors velocity sedimentation on 0.4-m KC1, 5–20% sucrose gradients prepared buffered deuterium oxide. Cytosol or unoccupied nuclear control grown...
Each year, influenza is responsible for hundreds of thousand cases illness and deaths worldwide. Due to the virus' fast mutation rate, World Health Organization (WHO) constantly on alert rapidly respond emerging pandemic strains. Although anti-viral therapies exist, most proficient way stop spread disease through vaccination. The majority vaccines market are produced in embryonic hen's eggs composed purified viral antigens from inactivated whole virus. This manufacturing system, however,...
BXH-2 mice develop a fatal myeloid leukemia by two-step mutagenic process. First, BXH-2–specific recessive mutation causes myeloproliferative syndrome. Second, retroviral insertions alter oncogenes or tumor suppressors, resulting in clonal expansion of leukemic cells. We have identified locus on chromosome 8 (Myls) that is responsible for myeloproliferation BXH-2. This Myls interval has been narrowed down to 2 Mb and found contain several positional candidates, including the interferon...
The NDT80/PhoG transcription factor family includes ScNdt80p, a key modulator of the progression meiotic division in Saccharomyces cerevisiae. In Candida albicans, member this family, CaNdt80p, modulates azole sensitivity by controlling expression ergosterol biosynthesis genes. We previously demonstrated that CaNdt80p promoter targets, addition to ERG genes, were significantly enriched genes related hyphal growth. Here, we report is indeed required for growth response different...
Candida albicans, the major fungal pathogen of humans, causes life-threatening infections in immunocompromised individuals. Due to limited available therapy options, this can frequently lead failure and emergence drug resistance. To improve current treatment strategies, we have combined comprehensive chemical-genomic screening Saccharomyces cerevisiae validation C. albicans with goal identifying compounds that couple fungistatic fluconazole make it fungicidal. Among genes identified yeast...
Abstract Fast and efficient production of recombinant proteins for structural functional studies is a crucial issue research industry. To this end, we have developed an system to generate in less than 2 months, starting from the cDNA, pools CHO cells stably expressing high‐level proteins. It based on lentiviral vectors (LVs) stable transduction coupled with cumate gene‐switch inducible gene expression. Transcription initiated upon binding transactivator (cTA) or reverse cTA (rcTA) CR5...
Effective biologic therapeutics require binding affinities that are fine-tuned to their disease-related molecular target. The ADAPT (Assisted Design of Antibody and Protein Therapeutics) platform aids in the selection mutants improve/modulate affinity antibodies other biologics. It uses a consensus z-score from three scoring functions interleaves computational predictions with experimental validation, significantly enhancing robustness design mutants. was tested on antibody Fab-antigen...
ABSTRACT Experimental infection of inbred mouse strains with Candida albicans provides a good model system to identify host genetic determinants that regulate onset of, response to, and ultimate outcome disseminated candidiasis. The A/J strain is exquisitely sensitive C. , while the C57BL/6J relatively resistant, as measured by survival following intravenous injection blastospores. This differential susceptibility caused an A/J-specific loss-of-function mutation in C5 component complement...
We have used chemical cross-linking and dense amino acid labeling of estrogen receptors to characterize the subunit nature rate turnover nuclear 5S estrogenreceptor complexes. When MCF-7 human breast cancer cells are incubated with [3H]estradiol or [3H]antiestrogen [a-[4-pyrrolidinoethoxy] phenyl-4-hydroxy-a-nitrostilbene (CI628M) (Z)- l-[4-(2-[iV-aziridinyl]ethoxy)phenyl]l,2-diphenyl-l-butene (tamoxifen aziridine)] estrogen-receptor complexes extracted 0.6 M KC1 then chemically cross-linked...
Candida albicans is a diploid fungal pathogen lacking defined complete sexual cycle, and thus has been refractory to standard forward genetic analysis. Instead, transcription profiling reverse strategies based on Saccharomyces cerevisiae have typically used link genes functions. To overcome restrictions inherent in such indirect approaches, we investigated mutagenesis strategy the UAU1 technology. We screened 4700 random insertion mutants for defects hyphal development linked two new (ARP2...
Summary Biofilm development by Candida albicans requires cell adhesion for the initial establishment of biofilm and continued stability after hyphal occurs; however, regulation process has not been fully established. Using chromatin immunoprecipitation coupled to microarray analysis (ChIP‐chip) we have characterized a regulon containing Mcm1p factor that is required surface during formation. In yeast Saccharomyces cerevisiae several regulons in which regulatory specificity achieved through...
Candida albicans is an opportunistic pathogen that causes acute disseminated infections in immunocompromised hosts, representing important cause of morbidity and mortality these patients. To study the genetic control susceptibility to C. mice, we phenotyped a group 23 phylogenetically distant inbred strains for infection as measured by extent fungal replication kidney 48 hours following infection. Susceptibility was strongly associated with loss-of-function mutant complement component 5...
We have used the technique of density labeling proteins by biosynthetic incorporation 2H, 13C, 15N (dense) amino acids to study synthesis and degradation rates progesterone receptor in MCF-7 human breast cancer cells. In cells grown absence progestin, sucrose gradient shift analyses reveal that it takes 17 h for normal levels be reduced half initial value, whereas presence 10 nM synthetic progestin [3H]R5020, turns over more rapidly, such R5020-occupied complexes are 12 h. The accelerated...
Abstract Plasmid transfection of mammalian cells is the dominant platform used to produce adeno‐associated virus (AAV) vectors for clinical and research applications. Low yields from this currently make it difficult supply these activities with adequate material. In an effort better understand current limitations transfection‐based manufacturing, study examines what proportion in a model appreciable amounts assembled AAV capsid. Using conformation‐specific antibody staining flow cytometry,...