Current Projects

• The Potential of Embryonic Stem Cell Derived Hepatocytes to Regenerate a Damaged Liver 
  Submitted by Valerie Gouon-Evans  (Mount Sinai School of Medicine Black Family Stem Cell Institute, New York City, NY, United States) 1/19/2010
  The capacity of embryonic stem (ES) cells to form multiple differentiated cell types in culture provides a unique model system for the generation of transplantable lineages and tissues for cell replacement therapies. For this potential to be realized, it was first essential to understand in this model system the events regulating the induction and specification of the three primary germ layers, ectoderm, mesoderm and endoderm, and significant progress toward that goal has been achieved. The long-term goal of this project is to define the subsequent mechanisms regulating the specification of embryonic stem (ES) cell-derived endoderm to a hepatic fate, and maturation to functional hepatocytes that are able to repopulate a diseased liver. For this study, we chose to use the fumarylacetoacetate hydrolase (FAH) deficient mouse model established by Dr. Markus Grompe. The FAH-deficient mouse serves as a model for hereditary tyrosinemia type I in humans. This mouse model lacks T cells, B cells, as well as NK cells and can be consequently used successfully for both mouse and human hepatocyte transplantation. However, to prevent any rejection of the transplanted hepatic cells, mice will be treated with clodronate to deplet the liver Kupffer cells. This study will characterize in a step-wise manner the liver regeneration process by embryonic stem cell-derived hepatic cells, providing essential insight into the limitations and advantages of using pluripotent stem cells for liver cell therapy.



• Unravelling the role of microglia in bilirubin-induced neurologic dysfunction (BIND): in vitro and ex vivo studies 
  Submitted by Dora Brites  (Faculdade de Farmacia da Universidade de Lisboa, Lisbon, Portugal) 1/19/2010
  Hyperbilirubinemia and kernicterus are re-emerging as prominent clinical concerns. Accurate intervention guidelines are missing, mechanisms of unconjugated bilirubin (UCB) neurotoxicity are unclear, as are specific biomarkers, and little is known about long-term effects of bilirubin-induced neurologic dysfunction (BIND). The BIND project aims to explore the pathophysiology of kernicterus and the brain sequelae resulting from moderate jaundice, using novel in vitro and ex vivo approaches, as well as target-directed therapies. It will be directed to the following crucial aspects: (i) the hippocampus, a classical damaged brain area in kernicterus; (ii) microglia, with a key role in neuroinflammation, activated upon UCB exposure (our pioneer study). To evaluate whether microglia potentiate UCB-induced damage we will use hippocampal slices, depleted or not from microglia and we will investigate glia reactivity, neurodegeneration, demielination and changes in synaptic activity after treatments. The use of glycoursodeoxycholic acid as a neuroprotective agent will be evaluated in our model. We expect to clarify whether neuroinflammation is a risk factor for kernicterus and to recognize new therapeutic immunomodulation capacities, thus contributing to define a consistent regimen for treatment and prevention of BIND.
  More: http://www.imed.ul.pt/Research/Neuron%20Glia%20Biology%20in%20Health%20and%20Disease.htm



• The immune mechanisms induced by DNA vaccine for T-cell priming  
  Submitted by Avi-Hai Hovav  (The Hebrew University, Jerusalem, Israel) 1/18/2010
  We are studying the role of DCs in antigen presentation following immunization with plasmid DNA
  More: http://dental.huji.ac.il/newEsite/departments/institute/instituteindex.html



• Tumor associated macrophage in immune suppression 
  Submitted by Yee-Shiuan Chen  (Washington University in St. Louis, St. Louis, MO, United States) 1/15/2010
  The cancer immunosurveillance hypothesis suggests that the immune system is critical for the detection and eradication of early tumors. However, it is also clear that many types of tumors are able to exert immunosuppressive effects, or recruit host immunosuppressive cells to aid in their escape. In tumor-bearing mice, a class of bone-marrow derived cells, known as myeloid-derived suppressor cells (MDSC), accumulate in the spleen as well as infiltrating the tumor itself. These cells are able to suppress T cell proliferation, and may represent a major escape mechanism for developing tumors. My project involves the characterization of these cells in the context of transplant tumor models, with focus on their development/differentiation and immune-suppression mechanisms.



• Role of macrophages in a mouse model of acute and chronic muscle damage 
  Submitted by Lidia Bosurgi  (San Raffaele Scientific Institute, Milan, Italy) 1/15/2010
  We are studying the role of different polarized macrophages populations in both in vitro and in vivo models of acute or sustained muscle damage, to verify the hierarchy of events linking the immune system to muscle regeneration and whether they represent suitable targets for molecular therapies.



• Macrophage depletion in subcutaneous tumors 
  Submitted by Thorbald Hall  (LUMC, Leiden, Netherlands, The) 1/15/2010
  Study what the effect is of presence of macrophages in subcutaneous melanoma growth.



• Macrophage Dependence Upon Epimorphic Regeneration 
  Submitted by Vineet Agrawal  (University of Pittsburgh, Pittsburgh, PA, United States) 1/13/2010
  In an adult murine model of digit amputation, we are interested in investigating what role, if any, the immune microenvironment plays in promoting epimorphic regeneration of an amputated phalanx of a digit in a murine hindfoot.



• Regulation of parasitaemia in mice infected with T. b. brucei  
  Submitted by Didier Salmon  (IBMM, Gosselies, Belgium) 1/13/2010
  # n this project, various T. brucei mutants of kinesine that affect the level of parasitaemia in mammalian host are currently being studied in different transgenic mice (nude, uMT, MyD88, ...) by analysis of the cytokine profile (IFgama, IL12, IL10, ...) and we plan to analyze the influence of phagocytic cells upon the reduction of parasitaemia by using the clodronate APC liposome strategy. We would like to perform a pilote experiment with two batches of mice: treated by free-liposomes and treated by clodronate liposomes. The Project is coordonated by Prof. E. Pays (ULB, IBMM, Lab of Molecular Parasitology)



• renal cancer 
  Submitted by alicia cole  (Beatson Institute for Cancer research, glasgow, United Kingdom) 12/1/2010
  investigating the loss of apc deficient cells by macrophage clearance from the kidney



• The role of macrophages in PGE2-dependent tumorigenesis in the stomach 
  Submitted by Masanobu Oshima  (Cancer Research Institute, Kanazawa University, Japan, Kanazawa, Japan) 1/10/2010
  We have constructed transgenic mouse model (Gan mice) that develop gastric tumors caused by simultaneous activation of Wnt and PGE2 pathways. In the gastric tumors of Gan mice, macrophages are infiltrated and activated in a PGE-dependent manner. By depleting macrophages by administration of clodronate-liposomes, we will investigate the role of macrophages in gastric tumorigenesis.