Theme 4: Integrated transcriptional analysis of liver diseases

Philippe LEFEBVRE

Research director 1, Inserm, Team leader

ORCID : 0000-0002-9366-5129

Philippe Lefebvre completed his PhD in Biochemistry at ULille1 in 1988, during which he studied the mechanism of action of anti-glucocorticoids under the supervision of Pr P. Formstecher. He then did his postdoctoral training in Dr G.L. Hager’s lab at N.I.H., N.C.I., Bethesda to study transcriptional mechanisms governing the glucocorticoid-driven, cell type-specific expression of the Mouse Mammary Tumor Virus (MMTV) and chromatin-regulated processes. Since 1992, he has been at INSERM in Lille where he is currently a research director. He first established a research group working mostly on nuclear retinoic acid receptors (RARs, RXRs) and orphan receptors structure and regulation (Nurr1, Nur77) in cellular differentiation and cancer. His scientific interests then switched towards the study of the role of nuclear receptors in cardiometabolic diseases, mostly focusing on PPARα and FXR.  He now leads a research group in Pr Bart Staels laboratory and, together with Dr Jérôme Eeckhoute, focuses mostly on nuclear receptor-regulated molecular mechanisms governing liver pathophysiology, with a specific emphasis on NASH and fibrosis.

Jérôme EECKHOUTE

Research director 2, CNRS

ORCID : 0000-0002-7222-9264

Jérôme Eeckhoute earned his PhD in molecular biology from the University of Lille in 2003 owing to studies defining the functional consequences of diabetes-associated mutations of the nuclear receptor HNF4A. He subsequently moved to the Dana-Farber cancer institute (Harvard Medical School, Boston, USA) where he was involved in defining the transcription factor hierarchy and interplay with chromatin involved in regulatory activities of the estrogen receptor. Ever since his recruitment by the CNRS in 2008, he has been focusing on applying functional genomics to decipher molecular mechanisms involved in (dys)regulation of cell/tissue-specific transcriptional regulatory programs with a special emphasis on nuclear receptors and chromatin/epigenomics. Recent interests lie in the characterization of molecular entities and mechanisms responsible for establishment and maintenance/loss of cell identity in liver pathophysiology

Viktorija AVILKINA

Postdoctoral fellow, Lille University

Alexandre BERTHIER

Postdoctoral fellow

ORCID : 0000-0003-4153-4810

Alexandre Berthier earned his PhD in Life Sciences (molecular aspects) from the University of Besançon in 2008, where he developed "biosensors/cellular models" tools for identifying ligands of the nuclear estrogen receptor (ERα) and studying DNA/protein and protein/protein interactions. He subsequently investigated AMP-regulated kinase (AMPK) in Grenoble as part of Professor Uwe Schlattner’s group before joining Dr. Philippe Lefebvre’s team at the University of Lille in 2010. His research focuses on the nuclear receptors FXR, PPARα, and REV-ERBα, and their roles in the circadian regulation of liver metabolism. He is particularly interested in the transcriptional mechanisms involved in metabolic-associated steatohepatitis (MASH) and liver fibrosis, exploring the molecular pathways underlying these conditions. He develops innovative approaches to unravel complex molecular interactions and metabolic mechanisms.

Desiree de BRUIN

Ph.D Student, Lille University

ORCID : 0009-0005-4186-4627

Desiree de Bruin will joint the team in February 2025 as PhD candidate, part of the MSCA MIRACLE Doctoral Network. Her project focuses on liver cell plasticity in MASH related inflammation and fibrosis. Her background is in molecular biology (bachelor) and forensic science (master). She worked as a research technician at the Hubrecht Institute (Utrecht, The Netherlands) in the group of prof. Dr. Geert Kops, focusing on endogenous tagging of cell cycle regulating proteins using CRISPR techniques and live cell imaging. After completing her master’s, she worked as a research associate at the Amsterdam University Medical Center (Amsterdam, The Netherlands) under the supervision of Dr. Peter Henneman, focusing on forensic (epi)genetics and third generation sequencing techniques.

Julie DUBOIS-CHEVALIER

Research Engineer, INSERM, Bioinformatics platform leader

ORCID : 0000-0003-0471-752X

Julie Dubois-Chevalier is a specialist in Bioinformatics and Machine Learning. She earned her PhD in Chemoinformatics at the University of Orléans in 2011, studying the concepts of molecular “diversity” and “representativity” to propose a molecules selection method for high throughput screening in drug discovery. She joined the team in 2012 for a post-doctoral fellow under the supervision of Jérôme Eeckhoute to study the role of transcription factors and their cooperation in defining the genesis of the adipocyte lineage. Since 2016, she is bioinformatics platform leader for the unit, developing and deploying tools to process omics data. She leverages her expertise in Machine Learning to study the epigenetic mechanisms involved in the control of hepatocyte identity by integrating heterogeneous omics data.

Sandra COURQUET

Engineer, Lille University

ORCID : 0000-0002-2442-3222

Sandra Courquet obtained her master's degree in Biology and Health Products, Host-Graft Relation pathway at the University of Besançon in 2017. She then joined the CNR Echinococcoses/UMR6249 Chrono-Environnement (Besançon), where her work focused mainly on monitoring the Echinococcus multilocularis parasite, responsible for the liver disease Alveolar Echinococcosis. Then, in 2022, she joined the Clinical Research Department of Medical Oncology (Besançon University Hospital) to ensure the follow-up and quality of phase I to IV clinical trials. In October 2024, she joined UMR1011 under the direction of Dr Philippe Lefebvre, to participate in the study of molecular mechanisms involved in liver pathologies.

Hélène DEHONDT

Engineer, Lille University

ORCID : 0000-0003-2900-4673

Hélène Dehondt obtained her Master's degree in Cellular and Molecular Biology in 2000 at the University of Lille. She was then employed by the CNRS in Strasbourg to develop a new technique for discriminating mutations in colorectal cancer, and to manage a European research sub-project to highlight the toxicity of products derived from fatty acid ionization. Building on this experience, she joined UMR1011 in 2001.  Her missions consist in two main areas: management of the technical platform and management of research projects aimed at understanding the molecular mechanisms involved in metabolic diseases.

Dmitry GALINOUSKY

Postdoctoral Fellow

ORCID : 0000-0002-2522-6052

Dmitry Galinousky is experienced in bioinformatics and data processing and is an expert in molecular genetics. Dmitry has developed approaches for predicting phenotypic traits based on omics data (transcriptomic, proteomic, and morphometric data). He has also examined the gut microbiome status of long-lived individuals. Dmitry joined the team in April 2024 thanks to a joined research program with the biopharmaceutical company Genfit. He is in charge of bulk and single-cell/nuclei RNA-seq data processing both using public and in-house datasets.

Céline GHEERAERT

Engineer, Lille University

ORCID : 0000-0003-4096-6363

Céline Gheeraert obtained a Master's degree in Cellular and Molecular Engineering from the University of Lille in 2006. She began her professional career at GENFIT, a biotechnology company based in Lille, where she contributed to projects focused on identifying novel pharmacological treatments for diseases associated with metabolic syndrome.

In 2008, she joined the unit under the supervision of Dr. Philippe Lefebvre as an engineer, where she developed expertise in cistrome analysis techniques and epigenomic modifications (ChIPseq, CUT&RUN, (h)MeDIPseq). She also set up and managed a gene expression microarray platform (Affymetrix technology) before evolving this technological approach towards the use of “new generation” sequencing (RNAseq/snRNAseq).

For several years, under the supervision of Dr. Jérôme Eeckhoute, she has focused on studying the transcriptional networks that regulate cell identity in liver pathophysiology. Her research particularly investigates the role of transcription factors in maintaining and modulating hepatic identity under both normal and pathological conditions.

Georgiana TOMA

Post-doctoral fellow

Numéro ORCID : 0000-0003-0356-9158

Ludivine VASSEUR

Ph.D Student, Lille University

ORCID : 0000-0001-5122-1717

After her obtaining her Master’s degree in Bioinfomatic, Omics and System Biology at Lille University in 2022, Ludivine Vasseur joined the UMR 1011 as a PhD Student under the supervision of Dr. Jérôme Eeckhoute. Her thesis focuses on the transcriptional control of the hepato-cholangiocyte plasticity, combining experimental approaches in cell and molecular biology as well as bioinformatic analyses. Ludivine stands out for in-depth mastery of integrated approaches covering all aspects of Omics (from data collection to biological analysis and comprehension).

Ninon VERY

Postdoctoral Fellow, Lille University

ORCID :  0000-0003-4250-5819

Ninon Very is a specialist in O-GlcNAcylation and its physiopathological role in chronic human diseases. She earned her Ph.D. in Molecular and Cellular Aspects of Biology from the University of Lille in 2020. Her doctoral research focused on the O-GlcNAcylation of Thymidylate Synthase, a mechanism involved in sensitization to 5-fluorouracil in colorectal cancer, conducted within UMR 8576 UGSF under the supervision of Prof. Ikram El Yazidi (team of Prof. Tony Lefebvre). Since 2020, she has joined U1011 under the direction of Dr. Jérôme Eeckhoute (team of Dr. Philippe Lefebvre) to pursue postdoctoral research. Her work explores the link between metabolic and transcriptional reprogramming governing the activation of fibrotic hepatic stellate cells through O-GlcNAcylation.

Manjula VINOD

Postdoctoral Fellow

Recent insights from our work:

1. Identify sex and time as main variables impacting on transcriptional dysregulation in Human metabolic dysfunction-associated steatotic liver disease (MASLD) (Vandel et al. Hepatology. 2020; Johanns et al. JHEP Rep 2024)
2. Unveil that hepatocyte identity is controlled by an extended array of transcription factors beyond the well-recognized core regulatory network including the thyroid hormone receptor beta (THRB) (Dubois-Chevalier et al. EMBO Rep 2023).
3. Identify the transcription factor BNC2 and its o-GlcNacylation as cornerstones in establishment of the myofibroblastic transcriptional program involved in development of liver fibrosis (Bobowski-Gerard M et al. Nat Commun, 2022; Very N et al. Cell Death & Dis 2024)

Team 4 form UMR1011 developped lot of scientific skills :

1. Multi-omics analysis of gene transcriptional regulation (Bulk and scRNAseq, ChIPseq, RIME, etc)
2. Bioinformatical data mining associated to the development of multi-omics analysis
3. In vivo and ex vivo modelisation of liver diseases (murine liver primary cells, murine models of liver diseases, ex vivo liver slices culture (PCLS))

Dr Philippe Lefebvre     

Research director, INSERM

philippe-claude.lefebvre[at]inserm.fr

Postal adress : Boulevard du Pr Jules Leclercq, Batiment J&K -Faculté de médecine - Pôle Recherche, 59045 Lille Cedex

Dr Jérôme Eeckhoute    

Research director, CNRS

jerôme.eeckhoute[at]inserm.fr

Postal adress : Boulevard du Pr Jules Leclercq, Batiment J&K -Faculté de médecine - Pôle Recherche, 59045 Lille Cedex