Michèle Rouleau

Université Laval

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Chantal Guillemette

Centre hospitalier de l'Université Laval

Guy G. Poirier

Université Laval

Laurent Villeneuve

Hospices Civils de Lyon

ÉL

Éric Lévesque

Université Laval

Patrick Caron

Centre hospitalier de l'Université Laval

Arnaud Droit

Université Laval

ÉP

Éric P. Allain

Université de Moncton

Michael J. Hendzel

University of Alberta

Véronique Turcotte

Université Laval

Adrien Labriet

Université Laval

Cooperative Institutions

Université Laval

Centre hospitalier universitaire de Québec

Centre hospitalier de l'Université Laval

Hôtel-Dieu de Québec

Quebec Research and Development Centre

University of Tübingen

University of North Carolina at Chapel Hill

Université de Montréal

Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology

Centre National de la Recherche Scientifique

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Quantitative profiling of the UGT transcriptome in human drug-metabolizing tissues

The Pharmacogenomics Journal (2017)

Alan Tourancheau Michèle Rouleau Sandra Guauque-Olarte Laurent Villeneuve Ian H. Gilbert

Proteome

RNA-Seq

10.1038/tpj.2017.5

Cite

Citations (36)

Post-transcriptional Regulation of UGT2B10 Hepatic Expression and Activity by Alternative Splicing

Drug Metabolism and Disposition (2018)

Adrien Labriet Éric P. Allain Michèle Rouleau Yannick Audet-Delage Laurent Villeneuve

The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines and heterocyclic amines, such as tobacco carcinogens and several antidepressants and antipsychotics. We hypothesized that alternative splicing (AS) constitutes a means to regulate steady-state levels of UGT2B10 and enzyme activity. We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals. The highest expression was in the liver, where 10 AS transcripts represented 50% of the UGT2B10 transcriptome in 50 normal livers and 44 hepatocellular carcinomas. One abundant class of transcripts involves a novel exonic sequence and leads to two alternative (alt.) variants with novel in-frame C termini of 10 or 65 amino acids. Their hepatic expression was highly variable among individuals, correlated with canonical transcript levels, and was 3.5-fold higher in tumors. Evidence for their translation in liver tissues was acquired by mass spectrometry. In cell models, they colocalized with the enzyme and influenced the conjugation of amitriptyline and levomedetomidine by repressing or activating the enzyme (40%–70%; P < 0.01) in a cell context–specific manner. A high turnover rate for the alt. proteins, regulated by the proteasome, was observed in contrast to the more stable UGT2B10 enzyme. Moreover, a drug-induced remodeling of UGT2B10 splicing was demonstrated in the HepaRG hepatic cell model, which favored alt. variants expression over the canonical transcript. Our findings support a significant contribution of AS in the regulation of UGT2B10 expression in the liver with an impact on enzyme activity.

Expression (computer science)

10.1124/dmd.117.079921

Cite

Citations (9)

PARP‐3 associates with polycomb group bodies and with components of the DNA damage repair machinery

Journal of Cellular Biochemistry (2006)

Michèle Rouleau Darin McDonald P Gagné M.‐E. Ouellet Arnaud Droit

Abstract Poly(ADP‐ribose) polymerase 3 (PARP‐3) is a novel member of the PARP family of enzymes that synthesize poly(ADP‐ribose) on themselves and other acceptor proteins. Very little is known about this PARP, which is closely related to PARP‐1 and PARP‐2. By sequence analysis, we find that PARP‐3 may be expressed in two isoforms which we studied in more detail to gain insight into their possible functions. We find that both PARP‐3 isoforms, transiently expressed as GFP or FLAG fusions, are nuclear. Detection of endogenous PARP‐3 with a specific antibody also shows a widespread nuclear distribution, appearing in numerous small foci and a small number of larger foci. Through co‐localization experiments and immunoprecipitations, the larger nuclear foci were identified as Polycomb group bodies (PcG bodies) and we found that PARP‐3 is part of Polycomb group protein complexes. Furthermore, using a proteomics approach, we determined that both PARP‐3 isoforms are part of complexes comprising DNA‐PKcs, PARP‐1, DNA ligase III, DNA ligase IV, Ku70, and Ku80. Our findings suggest that PARP‐3 is a nuclear protein involved in transcriptional silencing and in the cellular response to DNA damage. J. Cell. Biochem. 100: 385–401, 2007. © 2006 Wiley‐Liss, Inc.

Ku70

Ku80

10.1002/jcb.21051

Cite

Citations (112)

The liver proteome of individuals with a natural UGT2B17 complete deficiency

Scientific Reports (2025)

Michèle Rouleau Matthias Schwab Kathrin Klein Roman Tremmel Mathias Haag

Glucuronidation is a crucial pathway for the metabolism and detoxification of drugs and endobiotics, and primarily occurs in the liver. UGT2B17 is one of the 22 glycosyltransferases (UGT) that catalyze this reaction. In a large proportion of the population, UGT2B17 is absent due to complete gene deletion. We hypothesized that a UGT2B17 human deficiency affects the composition and function of the liver proteome, potentially provoking compensatory responses, and altering interconnected pathways and regulatory networks. The objective was to elucidate the liver proteome of UGT2B17-deficient individuals. Liver specimens from UGT2B17-deficient and proficient individuals were compared by mass spectrometry-based proteomics using data-independent acquisition. In UGT2B17-deficient livers, 80% of altered proteins showed increased abundance with a notable enrichment in various metabolic and chemical defense pathways, cellular stress and immune-related responses. Enzymes involved in the homeostasis of steroids, nicotinamide, carbohydrate and energy metabolism, and sugar pathways were also more abundant. Some of these changes support compensatory mechanisms, but do not involve other UGTs. An increased abundance of non-metabolic proteins suggests an adaptation to endoplasmic reticulum stress, and activation of immune responses. Data implies a disrupted hepatocellular homeostasis in UGT2B17-deficient individuals and offers new perspectives on functions and phenotypes associated with a complete UGT2B17 deficiency.

Proteome

10.1038/s41598-025-89160-4

Cite

Citations (0)

Untargeted metabolomics identifies metabolic dysregulation of sphingolipids associated with aggressive chronic lymphocytic leukaemia and poor survival

Clinical and Translational Medicine (2023)

Flora Nguyen Van Long Délya Valcourt‐Gendron Patrick Caron Michèle Rouleau Laurent Villeneuve

Abstract Background Metabolic dependencies of chronic lymphocytic leukaemia (CLL) cells may represent new personalized treatment approaches in patients harbouring unfavourable features. Methods Here, we used untargeted metabolomics and lipidomics analyses to isolate metabolomic features associated with aggressive CLL and poor survival outcomes. We initially focused on profiles associated with overexpression of the adverse metabolic marker glycosyltransferase (UGT2B17) associated with poor survival and drug resistance. Results Leukaemic B‐cell metabolomes indicated a significant perturbation in lipids, predominantly bio‐active sphingolipids. Expression of numerous enzyme‐encoding genes of sphingolipid biosynthesis pathways was significantly associated with shorter patient survival. Targeted metabolomics further exposed higher circulating levels of glucosylceramides (C16:0 GluCer) in CLL patients relative to healthy donors and an aggressive cancer biology. In multivariate analyses, C16:0 GluCer and sphinganine were independent prognostic markers and were inversely linked to treatment‐free survival. These two sphingolipid species function as antagonistic mediators, with sphinganine being pro‐apoptotic and GluCer being pro‐proliferative, tested in leukemic B‐CLL cell models. Blocking GluCer synthesis using ceramide glucosyltransferase inhibitors induced cell death and reduced the proliferative phenotype, which further sensitized a leukaemic B‐cell model to the anti‐leukaemics fludarabine and ibrutinib in vitro. Conclusions Specific sphingolipids may serve as prognostic markers in CLL, and inhibiting enzymatic pathways involved in their biosynthesis has potential as a therapaeutic approach.

Sphingolipid

10.1002/ctm2.1442

Cite

Citations (5)

Unravelling the transcriptomic landscape of the major phase II UDP-glucuronosyltransferase drug metabolizing pathway using targeted RNA sequencing

The Pharmacogenomics Journal (2015)

Alan Tourancheau Guillaume Margaillan Michèle Rouleau Ian H. Gilbert Laurent Villeneuve

Glucuronosyltransferase

Exon skipping

RNA-Seq

10.1038/tpj.2015.20

Cite

Citations (45)

Poly(ADP) Ribose Polymerase at the Interface of DNA Damage Signaling and DNA Repair

Springer eBooks (2012)

Jana Krietsch Michèle Rouleau Michel Lebel Guy G. Poirier Jean‐Yves Masson

10.1007/978-1-4614-4741-2_8

Cite

Citations (0)

PARP inhibition: PARP1 and beyond

Nature reviews. Cancer (2010)

Michèle Rouleau Anand G. Patel Michael J. Hendzel Scott H. Kaufmann Guy G. Poirier

PARP1

10.1038/nrc2812

Cite

Citations (1,254)

Reprogramming cellular events by poly(ADP-ribose)-binding proteins

Molecular Aspects of Medicine (2012)

Jana Krietsch Michèle Rouleau Émilie Pic Chantal Éthier Ted M. Dawson

Ribose

10.1016/j.mam.2012.12.005

Cite

Citations (157)

Alternative promoters control UGT2B17-dependent androgen catabolism in prostate cancer and its influence on progression

British Journal of Cancer (2020)

Éric Lévesque Adrien Labriet Hélène Hovington Éric P. Allain Luciana Melo-Garcia

Perturbation of the major UGT2B17-dependent androgen catabolism pathway has the potential to affect prostate cancer (PCa) progression. The objective was to evaluate UGT2B17 protein expression in primary tumours in relation to hormone levels, disease characteristics and cancer evolution.We conducted an analysis of a high-density prostate tumour tissue microarray consisting of 239 localised PCa cases treated by radical prostatectomy (RP). Cox proportional hazard ratio analysis was used to evaluate biochemical recurrence (BCR), and a linear regression model evaluated variations in circulating hormone levels measured by mass spectrometry. The transcriptome of UGT2B17 in PCa was established by using RNA-sequencing data.UGT2B17 expression in primary tumours was associated with node-positive disease at RP and linked to circulating levels of 3α-diol-17 glucuronide, a major circulating DHT metabolite produced by the UGT2B17 pathway. UGT2B17 was an independent prognostic factor linked to BCR after RP, and its overexpression was associated with development of metastasis. Finally, we demonstrated that distinctive alternative promoters dictate UGT2B17-dependent androgen catabolism in localised and metastatic PCa.The androgen-inactivating gene UGT2B17 is controlled by overlooked regulatory regions in PCa. UGT2B17 expression in primary tumours influences the steroidome, and is associated with relevant clinical outcomes, such as BCR and metastasis.

Biochemical recurrence

breakpoint cluster region

Dihydrotestosterone

10.1038/s41416-020-0749-2

Cite

Citations (15)