2025-2026 List of Master 2 internship subjects offered by the laboratory
Please find below the list of Master 2 internship subjects offered by UMR1011 :
Regulation of angiogenesis by mitochondrial protein import pathway.
Mitochondria play a pivotal role in bioenergetics, metabolism, and apoptosis. Since the mitochondrial genome encodes only 13 proteins, the proper function of these organelles relies on the import of more than 1000 nucleus-encoded proteins. A crucial component of the mitochondrial protein import machinery is the evolutionarily conserved CHCHD4 oxidoreductase, which facilitates the oxidative folding of imported proteins after they after they cross the outer mitochondrial membrane. This finely regulated process is disrupted in disease conditions. This project employs a multidisciplinary approach, integrating molecular and cellular biology techniques, to:
i) Investigate the role and functional significance of CHCHD4 in endothelial cells;
ii) Characterize the signaling pathways influencing the CHCHD4-dependent import pathway in pathological angiogenesis.
The central hypothesis is that dysregulation of this import mechanism contributes to aberrant angiogenesis. Insights from this study may pave the way for novel therapeutic strategies targeting vascular dysfunction in cardiovascular diseases such as atherosclerosis.
Master 2 courses :
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Anna Rita Cantelmo, PhD
anna-rita.cantelmouniv-lille.fr
U1011 - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires, Institut Pasteur de Lille - 1 Rue du Professeur Calmette - Lille Cedex
Tel: 03 20 33 70 78
PPARα and metabolic memory in diabetic retinopathy
Diabetes mellitus affects an increasing global population, with diabetic retinopathy (DR) and diabetic macular edema (DME) being major causes of vision loss. Endothelial dysfunction plays a pivotal role in DR, where chronic hyperglycemia drives persistent metabolic and epigenetic alterations, contributing to ‘metabolic memory’ and disease progression.
Peroxisome Proliferator-Activated Receptor α (PPARα) serves as a key regulator at the intersection of metabolism and epigenetics. While primarily involved in lipid metabolism, PPARα also modulates inflammatory responses and influences DNA methylation. In diabetes, its expression is repressed due to hypermethylation, which may contribute to sustained endothelial dysfunction. Notably, PPARα agonists have demonstrated protective effects in DR, raising the question of whether their benefits stem from epigenetic modulation rather than metabolic regulation alone.
This project aims to: (1) assess endothelial PPARα epigenetic alterations as potential markers of vascular dysfunction in diabetes, and (2) investigate the interplay between metabolic and epigenetic pathways via PPARα in retinal endothelial cells. This study seeks to uncover novel endothelial targets for therapeutic intervention in DR.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Anna Rita Cantelmo, David Dombrowicz
anna-rita.cantelmouniv-lille.fr
Tel: +33 320 87 71 48
U1011 - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires, Institut Pasteur de Lille - 1 Rue du Professeur Calmette - Lille Cedex
Metabolic control of IL-23 production by resident and migratory dendritic cells.
Background. Dendritic cells (DC) are key to the initiation of the adaptive immune response. They capture antigens in peripheral tissues and migrate to draining lymph nodes (LNs). In psoriasis (PSO), migrating IL-23-producing DCs activate T lymphocytes and IL-17 production in LNs. Metabolism controls key DC functions, and fatty acids exacerbate PSO through their effects on DCs, but the metabolic pathways governing these processes are poorly understood.
Aim. This project will investigate how DC metabolism and in particular the pentose phosphate (PPP) and hexosamine biosynthesis (HBP) pathways affect these parameters to induce psoriasis and contribute to their exacerbation in metabolic pathologies.
Methods. Preclinical in vivo and in vitro models, pharmacological inhibitors and gene modifications will be used to study a) the metabolic requirements of IL-23-producing DCs b) metabolic remodeling during exacerbation of psoriasis by a high-fat diet. The study will focus on enzymes controlling glycolysis and PPP respectively: Pfkfb3 and HBP: Gfpt1, Stt3a. Metabolic analyses based on flow cytometry (SCENITH) and transcriptomic analyses by scRNA-seq will be used.
Collaborations. This work will be undertaken in collaboration wtih Dr Stoyan Invanov (LP2M, Nice).
Keywords. DC, Psoriasis, Métabolism, scRNA-seq, bioinformatic, functionnal tests
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
David DOMBROWICZ, DR Inserm
david.dombrowiczpasteur-lille.fr
UMR 1011. Institut Pasteur de Lille. 1 rue du Pr Calmette. 59019 Lille.
0320877967
Role of CX3CR1+ T lymphocytes in metabolic diseases
Context. CD4+ and CD8+ T lymphocytes are major players in adaptive immunity and play diverse roles in the development of metabolic diseases such as obesity, type 2 diabetes and metabolic fatty liver. In liver and adipose tissue, a T lymphocyte subpopulation expresses the CX3CR1 receptor, a receptor for the CX3CL1 chemokine involved in adhesion, migration, tissue retention and cell survival. The role of these CD4+ and CD8+ T lymphocyte subpopulations in the development of metabolic diseases is currently unknown.
Aim. In this project, a characterization and functional study of these subpopulations will be carried out.
Methods. The project will be based primarily on mouse models of obesity and steatosis/steatohepatitis (HFD, HFSCD and CDAA diets) and on flow cytometry. Other techniques such as cell culture, ELISA and RT-PCR as well as transcriptomic approaches (RNA-seq and scRNA-seq) will be used. Ultimately, the project should shed light on the role of these CD4+ and CD8+ T lymphocyte subpopulations in the development of metabolic diseases.
Keywords. T lymphocytes, metabolic diseases, MASLD, MASH, fractalkine.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
David DOMBROWICZ, DR Inserm / Laurent L’HOMME
david.dombrowiczpasteur-lille.fr / laurent.l-hommeinserm.fr
UMR 1011. Institut Pasteur de Lille. 1 rue du Pr Calmette. 59019 Lille
0320877967
Identification of FAT10 interaction partners involved in hepatocyte injury through a proteomic approach
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects about one-third of the general population, with obesity being the primary risk factor. This condition is characterized by the accumulation of lipids in the liver (steatosis), which can progress to metabolic dysfunction-associated steatohepatitis (MASH). This condition can lead to the development of cirrhosis and hepatocellular carcinoma (HCC). To date, there are few effective pharmacological treatments for MASH, likely due to resistance mechanisms. Disruptions in protein degradation pathways, leading to the formation of Mallory-Denk bodies (MDB) and hepatocyte ballooning, typical markers of liver damage, may play a key role in the progression of MASH to cirrhosis and HCC. Our transcriptomic analyses of liver biopsies from obese patients with MASH reveal that FAT10 expression is positively correlated with MASLD severity. FAT10, a protein belonging to the "ubiquitin-like" family, is involved in FATylation, a process regulating protein degradation, and is induced by inflammation in metabolic tissues. Studies in mice show that FAT10 is involved in the formation of MDB induced by the hepatotoxin DDC, suggesting it may also play a similar role in the progression of MASH. Our project aims to characterize the role of FAT10 in hepatocyte injury during the progression of MASH. Identifying its interaction partners through a proteomic approach will help characterize the molecular pathways involved in liver damage and understand the role of FATylation in this process, with the hope of identifying new therapeutic targets.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Dr. Audrey Helleboid
audrey.helleboiduniv-lille.fr
INSERM-UMR1011 "Nuclear receptor, metabolic and cardiovascular diseases”
Laboratory J&K-Faculty of Medicine, Research Center-Bd Pr Jules Leclerc, Lille
Evaluation of pharmacological therapies for MASH, liver fibrosis and atherosclerosis in a new preclinical mouse model combining MASLD and atherosclerosis development
MASLD (Metabolic Dysfunction Associated Steatotic Liver Disease) is the most common liver disease in the world, with a prevalence estimated at 25% of the general population, but reaching 80-90% in obese adults and 50-70% in patients with type 2 diabetes. This pathology has now become a veritable global “epidemic” whose incidence continues to increase, in parallel with the growing epidemic of obesity and diabetes. MASLD is characterized in its first stage by an excessive accumulation of fat in the liver, considered as benign steatosis, in the absence of excessive alcohol consumption and in conjunction with cardiometabolic risk factors. During the progression of MASLD, simple steatosis can progress to MASH (Metabolic dysfunction-associated steatohepatitis), diagnosed as a combination of steatosis, inflammation and ballooning of hepatocytes. In the worst cases, liver damage can progress to fibrosis, cirrhosis and hepatocellular carcinoma, which can lead to the death of the patient. However, the majority of MASLD patients die from cardiovascular diseases. Currently, there is only one pharmacological treatment, resmetirom, approved in the USA for MASH, the aggressive form of MASLD.
In the laboratory, we have set up a new mouse model which progressively develops all stages of human MASLD pathology (liver steatosis, inflammation, ballooning and fibrosis) under high fat diet in a short period of time. The project aims to better understand MASH and liver fibrosis physiopathology and to test novel therapeutic targets for MASLD and its consequences on atherosclerosis development in this model. Histological, biochemical and molecular analyzes will be carried out on the various technical platforms of the laboratory.
Master 2 courses :
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Dr Fanny Lalloyer
fanny.lalloyeruniv-lille.fr
Inserm UMR 1011 - Institut Pasteur of Lille - University of Lille
03320877996
The role of ER-mitochondria contact sites (MAM) in GLP-1 secretion by L cells in the human intestinal organoid model
Type 2 diabetes, linked to dysregulation of glucose metabolism, is a global health emergency. In long term, it can lead to cardiometabolic complications.
The intestine plays a major endocrine role by secreting hormones including the incretin GLP-1 (Glucagon-Like Peptide 1), which ensures glycaemic balance by potentiating the secretion of insulin by pancreatic β-cell in response to glucose (Lu et al., 2021). The contact sites between the endoplasmic reticulum and mitochondria (MAM: Mitochondria-Associated Membranes) and their dynamics are essential for ensuring insulin sensitivity in liver and muscle and insulin secretion by the pancreas (Rieusset, 2018). Preliminary in vitro results in a murine L cell line show that MAMs are also involved in GLP-1 secretion.
The aim of the M2 internship is to study the role of MAMs in GLP-1 secretion by intestinal L cells using an original and complex ex vivo model of human intestinal organoids. The organoids will be exposed to various GLP-1 secretagogues (glucose, bile acids, fatty acids, amino acids, etc.). GLP-1 will be measured by ELISA in the supernatant and MAMs will be quantified by PLA (Proximity Ligation Assay) specifically in L cells using GLP-1 immunolocalization. These techniques are mastered in the laboratory. Following the development of adenovirus transfection of organoids, MAMs will be inhibited by a protein, the FATE1 spacer, in order to confirm the role of MAMs in GLP-1 secretion by human intestinal epithelium.
These results should help to position MAMs as potential therapeutic targets in type 2 diabetes to restore insulin sensitivity and increase insulin secretion.
Master 2 courses :
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Sophie LESTAVEL
sophie.lestaveluniv-lille.fr
UMR 1011 INSERM (Dir. Bart STAELS) - Laboratoire J&K, Pôle Recherche Faculté de Médecine, Boulevard du Pr Jules Leclercq 59000 Lille
Role of « ubiquitin-like protein » FAT10 in the hepatocyte suffering during MASH development
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 1/3 of the general population, which obesity is the main risk factor. MASLDs are characterized by an intrahepatic accumulation of lipids (steatosis) progressing to metabolic dysfunction-associated steatohepatitis (MASH) which can lead to the development of cirrhosis and hepatocellular carcinoma (HCC). To date, few effective medical treatments for MASH are available due to potential resistance to therapy. The disruption of degradation pathways leading to the formation of aggresomes: the Mallory-Denk-Bodies (MDB), and hepatocyte ballooning, the main histological characteristic of hepatocyte suffering, appears to be a potential mediator of the progression of MASH to cirrhosis and HCC. However, molecular mechanisms contributing to their formation are not known. Our transcriptomic analysis of liver biopsies from obese patients with MASH shows that FAT10 expression correlates positively with different histological grades of MASLD and MASH severity such as MDB. Interestingly, FAT10 is a protein of the “ubiquitin-like” family involved in FATylation processes regulating protein degradation, and is induced by inflammation in metabolic tissues. Interestingly, FAT10 plays a role in the formation of MDB induced by the hepatotoxic agent (DDC) in mice, suggesting that FAT10 may play a role in MDB formation during MASH progression. Our project therefore aims to characterize the role of FAT10 in the formation of MDB and hepatocyte suffering during the MASH severity in murine et human cellular models. This project will identify cellular and molecular mechanisms contributing to the hepatocyte suffering associated to MASH development and progression to cirrhosis and may lead to the identification of new therapeutic targets.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Pr Réjane Paumelle-Lestrelin
rejane.lestrelinuniv-lille.fr
03 20 97 42 09
INSERM-UMR1011 "Nuclear receptor, metabolic and cardiovascular diseases”
Laboratory J&K-Faculty of Medicine, Research Center-Bd Pr Jules Leclerc, Lille
Role of « ubiquitin-like protein » FAT10 in the development of hepatic insulin resistance during MASH
Metabolic associated steatotic liver disease (MASLD) is now considered the hepatic component of metabolic syndrome and is associated with the development of insulin resistance (IR). This IR is defined as the reduction in the cellular and tissue response to insulin and develops following an accumulation of hepatic triglycerides (steatosis) and chronic inflammatory stress, characteristics of metabolic steatohepatitis (MASH), at high risk of rapid progression to cirrhosis. Although there are clear links, the mechanisms contributing to the development of MASH and hepatic IR remain complex and still poorly understood. Interestingly, transcriptomic analysis of liver biopsies from obese patients developing different grades of MASLD showed that FAT10/UBD expression was positively correlated with MASH severity. Modulation of FAT10 expression in human and murine hepatocytes decreases lipid droplet accumulation during MASLD, and FAT10 deficiency in aged mice has been shown to promote insulin sensitivity, suggesting that FAT10 may contribute to the development of hepatic IR. However, no study to date has demonstrated a direct role for FAT10 in the regulation of the insulin signaling pathway and the development of hepatic IR during MASH. In order to better understand the role of FAT10 in the development of IR during MASH, we propose as part of Master 2, 1) to study the role of FAT10 and its mechanism of action in the response hepatocytes to insulin and IR in a context of MASH in vitro, 2) to determine the clinical relevance of FAT10 expression in hepatocytes associated with type 2 diabetes status in liver biopsies from obese patients with or without MASH.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact :
Pr Réjane Paumelle-Lestrelin and Dr Guillaume Lassailly (U1286)
rejane.lestrelinuniv-lille.fr
03 20 97 42 09
INSERM-UMR1011 "Nuclear receptor, metabolic and cardiovascular diseases”
Laboratory J&K-Faculty of Medicine, Research Center-Bd Pr Jules Leclerc, Lille
Role of the nuclear receptor Rev-erbα in angiogenesis
Atherosclerosis is a chronic inflammatory disease of large vessels triggered by the accumulation of cholesterol and leukocytes in the vascular wall. During atherogenesis, vascular wall thickening induces local hypoxia and promotes the vasa vasorum expansion by angiogenesis. These neovessels are however immature and then promote leakage of lipids and leukocytes thus contributing to plaque progression and rupture. The molecular and cellular mechanisms involved in the growth of the perivascular blood network are not known. Reducing its expansion could, however, represent an innovative therapeutic strategy in the treatment of these diseases. Our preliminary data suggest that the nuclear receptor Rev-erb-α controls angiogenesis and intraplaque neovascularization ex vivo and in vivo. This proposal aims to determine the impact of Rev-erb-α in endothelial cells during angiogenesis using in vivo and in vitro approaches. For that purpose, angiogenesis will be assessed in vivo by confocal and light sheet microscopy in endothelial-specific Rev-erbα-/- mice and their control by analyzing the development of the vascular network of newborn retinas. The role of Rev-erb-α on angiogenic processes will then be analyzed in vitro using 3D spheroid models of cell competition. The pathways involved in angiogenesis will be assessed in tissues and cultured cells by WES and RT-qPCR. This M2R proposal aims to determine the impact of Rev-erb-α in angiogenesis during atherosclerosis and to define the molecular and cellular mechanisms involved.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact:
Benoit Pourcet
benoit.pourcetuniv-lille.fr
Université de Lille INSERM U1011 Institut Pasteur de Lille CHU Lille EGID
01 rue du Pr Calmette – 0320877125
Muscle regeneration and metabolic disorder: contribution of the circadian clock
Obesity is a major public health issue, associated with metabolic disorders such as type 2 diabetes (T2D) and metabolic fatty liver disease (MFLD). Skeletal muscle plays a key role in glucose uptake, and its dysfunction contributes to insulin resistance and metabolic complications. The circadian clock regulates numerous physiological functions, and its disruption favours the development of metabolic pathologies. Conversely, obesity alters the biological clock, aggravating these disorders. One of the special features of skeletal muscle is its ability to regenerate following damage caused by intensive exercise or injury. This process requires the presence of muscle stem cells as well as the activation of an inflammatory response, which is essential for a return to tissue homeostasis. Various studies have shown that metabolic pathologies such as obesity or T2D are associated with defects in skeletal muscle regeneration, caused in particular by muscle stem cell dysfunction. However, the role of the immune system in this context remains unexplored. The aim of this project is to study the influence of the biological clock of immune cells, in particular macrophages, on the muscle regeneration process in an obesogenic and diabetogenic context. To answer this question, mice invalidated or specifically overexpressing the clock component Rev-erbα in macrophages will be fed high-fat or controlled diets and then subjected to muscle injury. The muscle regeneration process will be studied by histological analysis and immunophenotyping using muscle flow cytometry. Mechanistic, molecular and cellular studies may be carried out to clarify the mechanisms involved.
Master 2 courses:
- Diabetes and cardiovascular diseases
- Precision Health
Contact:
Dr. Yasmine Sebti
yasmine.sebtiuniv-lille.fr
Université de Lille INSERM U1011 Institut Pasteur de Lille CHU Lille EGID
01 rue du Pr Calmette
0320877125