A5068609421- Estrogen and related hormone effects
- Bioinformatics and Genomic Networks
- CRISPR and Genetic Engineering
- Gene expression and cancer classification
- Nutrition, Genetics, and Disease
- Genomics and Chromatin Dynamics
- Pluripotent Stem Cells Research
- Blood groups and transfusion
- Erythrocyte Function and Pathophysiology
- RNA Research and Splicing
- Nuclear Receptors and Signaling
- Hemoglobinopathies and Related Disorders
- Blood disorders and treatments
- Autism Spectrum Disorder Research
- Attachment and Relationship Dynamics
- Pancreatic function and diabetes
- Peroxisome Proliferator-Activated Receptors
- Genetic Neurodegenerative Diseases
- Virus-based gene therapy research
- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- Glutathione Transferases and Polymorphisms
- Infant Development and Preterm Care
- Cytokine Signaling Pathways and Interactions
- Nerve injury and regeneration
Héma-Québec
2017-2025
Université Laval
2002-2025
Sangamo BioSciences (United States)
2010-2019
Point Richmond Tech Center
2010-2013
Laboratoire de Biochimie
2009
McGill University
2004-2007
McGill University Health Centre
2003-2006
Montreal Clinical Research Institute
2005
Pediatric Oncology Group
2005
Hôpital du Saint-Sacrement
2004
Nuclear receptors can activate diverse biological pathways within a target cell in response to their cognate ligands, but how this compartmentalization is achieved at the level of gene regulation poorly understood. We used genome-wide analysis promoter occupancy by estrogen receptor α (ERα) MCF-7 cells investigate molecular mechanisms underlying action 17β-estradiol (E 2 ) controlling growth breast cancer cells. identified 153 promoters bound ERα presence E . Motif-finding algorithms...
The identification of regulatory regions is one the most important and challenging problems toward functional annotation human genome. In higher eukaryotes, transcription-factor (TF) binding sites are often organized in clusters called cis-regulatory modules (CRM). While prediction individual TF-binding a notoriously difficult problem, CRM has proven to be somewhat more reliable. Starting from set predicted for than 200 TF families documented Transfac, we describe an algorithm relying on...
Macrophage activation by the proinflammatory cytokine interferon-gamma (IFN-gamma) is a critical component of host innate response to bacterial pathogenesis. However, precise nature IFN-gamma-induced pathway not known. Here we show using genome-wide expression and chromatin-binding profiling that IFN-gamma induces many nuclear genes encoding mitochondrial respiratory chain machinery via receptor ERR alpha (estrogen-related alpha, NR3B1). Studies with macrophages lacking demonstrate it...
Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor, the expression of which correlates with negative prognosis in breast cancer. ERRalpha shares functional features estrogen (ERalpha) and its activity modulated by ERBB2 signaling pathway. Using genome-wide binding sites location analyses ERalpha-positive ERalpha-negative cancer cell lines, we show that ERalpha display strict site specificity maintain independent mechanisms transcriptional activation. Nonetheless,...
The orphan nuclear estrogen-related receptor alpha (ERRalpha) and transcriptional cofactor peroxisome proliferator-activated gamma coactivator-1alpha (PGC-1alpha) are involved in the regulation of energy metabolism. Recently, extensive cross-talk between PGC-1alpha ERRalpha has been demonstrated. presence is associated with an elevated expression ERRalpha, two proteins can influence activities one another. Using a candidate gene approach to detect regulatory variants within genes encoding...
Loss of dopaminergic neurons is primarily responsible for the onset and progression Parkinson's disease (PD); thus, neuroprotective and/or neuroregenerative strategies remain critical to treatment this increasingly prevalent disease. Here we explore a novel approach neurotrophic factor-based therapy by engineering zinc finger protein transcription factors (ZFP TFs) that activate expression endogenous glial cell line-derived factor (GDNF) gene. We show GDNF activation can be achieved with...
The identification of estrogen receptor (ERalpha) target genes is crucial to our understanding its predominant role in breast cancer. In this study, we used a chromatin immunoprecipitation (ChIP)-cloning strategy identify ERalpha-regulatory modules and associated the human cancer cell line MCF-7. We isolated 12 transcriptionally active genomic that recruit ERalpha coactivator steroid (SRC)-3 different intensities vivo. One identified located 3.7 kb downstream first transcriptional start site...
The estrogen-related receptors (ERRalpha, -beta, and -gamma) are a subfamily of orphan nuclear (designated NR3B1, NR3B2, NR3B3) that structurally functionally related to estrogen alpha beta. Herein we test the hypothesis ERRalpha regulates transcription genes encoding enzymes involved in adrenal steroid production. Real-time RT-PCR was first used determine levels mRNA various human tissues. Adult transcript were similar seen heart, which is known highly express ERRalpha. Expression adult...
The common practice of blood transfusion entirely relies on donations from the population. Ensuring group compatibility between a donor and recipient is paramount to prevent critical adverse reactions. Finding compatible can be challenging given high diversity antigens, especially for chronically transfused patients at higher risk alloimmunization owing repeated exposures foreign RBCs. In addition, due immunogenicity ABO highly polymorphic nature Rhesus (Rh) system, they both remain prime...
The orphan nuclear receptor estrogen-related alpha (ERRalpha, NR3B1) is a constitutively active transcription factor that controls multiple processes, most notably mitochondrial function. ERRalpha preferentially binds to nine-nucleotide extended half-site sequence TNAAGGTCA, referred as the ERRE, either monomer or dimer, although how mode of DNA binding dictated remains be determined. Here, we used variants and selective domain mutants investigate effects ERRE specificity on mode,...
Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a cell agonist in AA2P optimize series cocktails (SCACs) to help promote robust human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention function immature HSPC. show AA2P-mediated HSPC driven through DNA demethylation leading enhanced expression AXL...
Abstract Background The determination of the RhD phenotype is crucial to avoid alloimmunization, especially in childbearing women. Following 2015 recommendation from Work Group on RHD Genotyping, a large‐scale genotyping program was implemented province Quebec (Canada) and offered women ≤45 years old with serological weak D or discordant results. Since type 42 previously shown be prevalent among French Canadians, for that variant also performed. Our aim report prevalence alleles Quebec....
ABSTRACT Chimeric antigen receptors (CARs) reprogram T cells to recognize and target cancer cells. Despite remarkable responses observed with CAR-T cell therapy in patients hematological malignancies, engineering still relies mostly on randomly integrating vectors, limiting the possibilities of fine-tuning function. Here, we designed a CRISPR-based marker-free selection strategy simultaneously therapeutic transgene gain-of-function mutation MTOR locus enrich resistant rapamycin, clinically...
Abstract This study investigated attachment security and behavior in 34 physically disabled infants 26 non‐disabled by using convergent, categorical (secure, avoidant ambivalent) continuous (Attachment Behavior Q‐Set) measures of the relationship, based on same set home observations. Proportions classifications were not different for infants, but insecure group scored consistently lower AQS score than infants. result suggests that while proportions may vary as a function infant status, are...
ABSTRACT Targeted genome editing using engineered nucleases facilitates the creation of bona fide cellular models for biological research and may be applied to human cell-based therapies. Broadly applicable versatile methods increasing levels gene in cell populations remain highly desirable due variable efficiency between distinct genomic loci types. Harnessing multiplexing capabilities CRISPR-Cas9 Cpf1 systems, we designed a simple robust co-selection strategy enriching cells harboring...
Weak D type 42 accounts for an unusually high proportion of weak phenotypes in Québec (Canada), which contrasts with other predominantly White populations. However, its prevalence the general population is unknown. We estimated and common Québec.We screened RHD*01W.42 alleles among 1000 individuals CARTaGENE-a cohort representative Québec's population. The was calculated based on allele frequency d (i.e., all recessive that confer a D- phenotype), assuming Hardy-Weinberg equilibrium. This...