Institut André lwoff
The Institute of A. Lwoff (IAL) has been a Federative Structure of Research (SFR) at the University Paris-Sud 11 since 2010. It was created through the extremely strong dynamic teams involved in the Paul Brousse hospital site. It has enabled the convergence of basic, translational, and clinical research in the fields of hepatology, onco-hematology, and nephrology, with these specialties grouped together within the same center (MAFDU) in Paris Sud Medical School. The research teams have developed specific but complementary projects on common themes involving stem cells, regenerative medicine, and carcinogenesis, which has enabled significant synergy to develop.
The center is composed of three units (UMR-S 935, Dir Annelise Bennaceur-Griscelli "Stem cells, cancer, and chronotherapy"; UMR-S 1193 Dir Didier Samuel, "Carcinogenesis, transplantation, and liver regeneration"; and UMR-S 1197 Dir Georges Uzan, " Interactions between stem cells and their niches in physiology, tumors and tissue repair" The center has the advantage of blending INSERM and military departments, including the Health Department of the Armies and its research laboratories involved in stem cell research and therapy, plus a mixed service unit (UMS 33, Dir François Le Naour). Its evolution in recent years has been marked by the development of common research interests in stem cells and cancer.
All units at the Institute of A. Lwoff (IAL) are identifiable by their research topics, which are related to cancer and stem cells, with all medical staff having a long tradition in research on these subjects.
• Stem cells are studied in all three units. This research integrates the role of the microenvironment into a model of hematopoietic niches, and endothelial and hematopoietic stem-cell development, as well as the development of lympho-myeloid differentiation (Georges Uzan Team and Caroline Bousse-kerdiles, UMR-S 1197). The group run by Antoine Durrbach and Hans Lorenzo (UMR-S 1197) focuses on stem-cell behavior in several glomerular kidney diseases. The group of Anne-Dubart Kupperschmit (UMR-S 1193) studies liver stem cells and their microenvironment with a perspective towards liver reconstruction. A therapeutic approach has been developed using embryonic and fetal Mesenchymal Stem Cells (MSCs) to treat allograft rejection and severe burns (in collaboration with the military health service) (teams run by Antoine Dürrbach and Jean -Jacques Lataillade, UMR-S 1197).
• Cancer stem cells are another important source of stem cells involved in leukemic hematopoiesis (Team Ali Turhan, UMR-S 935 and the Caroline Bousse-Kerdilès, UMR-S 1197) liver cancer (UMR-S 1193) and kidney cancer (UMR-S 1197) (Julien Giron-Michel). Oncogenesis is a recurring theme in the A. Lwoff Institute, and a major aspect of future project of IAL including cancerous stem cells studies, tumor cell development from precancerous stages to metastatic spread, and circadian clocks. The influence of the microenvironment on tumor progression is more specifically addressed by teams run by Eric Rubinstein (UMR-S 935) and Christian Pous (UMR-S 1193) ("The role of chronic inflammation and oxidative stress in the development of liver cancer, colorectal carcinogenesis and inflammation; integrin receptor signaling collagen I, E-cadherin, tetraspanins).
The group run by René Adam (UMR-S 935) investigates the roles of genes involved in circadian clocks using experimental models and clinical tumors and, in particular, in colorectal cancer and its pharmacological and therapeutic implications. Several teams of UMR-S 1193 (Dir D. Samuel) are interested in hepatocellular carcinoma and cholangiocarcinoma, with studies mainly based on a proteomic approach. For hematology, myeloproliferative disorders, such as myeloid splenomegaly, are one of the major research areas of UMR-S 1197 (Dir G. Uzan) and the implications of immune regulation (IL-15) and differentiation of kidney cancer are major themes of UMR-S 1197.
• Several infectious diseases, mostly involved in oncogenesis, are studied mainly in relation to liver disease: i.e., HBV–HCV infection, hepatocellular carcinoma, liver transplantation, HCV genetic variability, HCV capsid proteins, and TGF β (UMR-S 1193). Alterations to the intestinal flora are being analyzed in connection with the development of hepatocellular carcinoma (Team Jamilla Faivre, Caroline Bousse-kerdiles, UMR S 1197)
• Apoptosis and cell survival are key points in cell survival and involve many pathways. The role of mitochondrial activation to cell survival and the proteins bcl2 family are being studied in tumor B-cell-related diseases and to prevent allograft rejection (UMR-S in 1193 and 1197) (Damien Arnoult).
Technical equipment, mostly concentrated within the Mixed Unit of Services (UMS 33), has been renewed with a Leica confocal microscope (SP5 model) in 2010, an Orbitrap Velos mass spectrometer in 2011, and a cell sorter in 2013.
The presence on-site of animal facilities (UPS44) (RIO platform) and a Nod-Scid animal facility (Inserm Lavoisier) is also a tremendous asset. The experimental animal facility in the Lavoisier building has been completely renovated and restructured, and has received accreditation for 6 years. Imaging of small animals has been acquired, particularly a luminescence scanner (IVIS Spectrum).
The platform for human embryonic pluripotent stem cells (ESTeam, A. Bennaceur-Griscelli) reinforces the potential for stem-cell research, but also more widely in the context of future investment, which now includes several French INGESTEM platforms coordinated by ESTeam.
Translational research activities continue to grow in relation to the clinical department in AP-HP and are particularly successful in the fields of liver and renal diseases and cancers. Hepatic pathophysiology is also conducted on site. This is integrated in the DHU Hepatinov (Director Jean-Charles Duclos-Vallée), which includes department and units from the Paris Sud University Medical School.
These units are also deeply involved in educational doctoral schools (especially focused on Cancer, Cell signaling (Biosigne), and Therapeutic Innovation) and training activities (Masters) at the Paris-Sud University.
Finally, IAL have developed numerous interactions with its immediate neighbors at Bicêtre Hospital, i.e., the Gustave Roussy Institute, the business incubator Biopark of Villejuif, and the epidemiological centers of Villejuif and Evry Genopole. IAL is part of the Faculty of Medicine and the University Paris-Saclay, and an international center for education and global research.
Prof. Antoine Durrbach, Director