Current Projects

• Role of macrophages in CD4+ T cell mediated tumor protection 
  Submitted by Simpson Tyler  (Memorial Sloan-Kettering Cancer Center, New York, NY, United States) 4/28/2010
  We have previously shown that adoptive transfer of tumor reactive CD4+ T cells into lymphopenic mice results in elimination of large established B16 melanoma due to direct recognition and killing by the transferred CD4+ T cells. In absence of irradiation but in combination with tumor-cell based vaccines, adoptive transfer of tumor reactive CD4+ T cells also results in tumor rejection, but not via direct recognition and killing of tumor cells. We would like to assess whether there is a role for macrophages in CD4+ mediated tumor protection. To evaluate a role for macrophages, we will deplete macrophages using clodronate loaded liposomes.



• Targeting tumour associated macrophages 
  Submitted by TOBY LAWRENCE  (Inserm, Marseille, France) 4/28/2010
  We are investigating the role of tumour associated macrophages in carcinogenesis using genetic mouse models of cancer.



• Role of Kupffer cells in liver fibrosis associated with ARPKD 
  Submitted by Jessica Wen  (University of Pennsylvania, Philadelphia, PA, United States) 4/27/2010
  We are interested in studying the role of Kupffer cells in modulating liver fibrosis in the disease Autosomal Recessive Polycystic Kidney Disease(ARPKD). Inactivation of Kupffer cells will be carried out in the animal model, PCK rats.



• Effect of Bone Morphogenetic Protein-6 on macrophages. 
  Submitted by Jae-Ho Lee  (The Cancer Institute of New Jersey, New Brunswick, United States) 4/26/2010
  Bone Morphogenetic Proteins (BMPs) were initially isolated and characterized as proteins that induce bone and cartilage formation. . Recently, BMP-6 has been reported to play a role in immune system, inhibit T cell proliferation and activate the macrophages. The emerging data suggest that BMPs play a more diverse role than just merely regulating bone metabolism during carcinogenesis. We speculated that effect of BMP-6 on tumor growth may related to immune modulation. In previous study, we showed that BMP-6 can activate macrophages and changed tumor growth. Thus, we speculate that BMP-6 is a key regulators of tumor microenvironment and effect of BMP-6 mediated by macrophages. Thus, in vivo tumor growth model for the interaction of BMP-6 and macrophages is need to be address. To this end, we plan to study role of macrophages in tumor growth in presence or absence of BMP-6. The major hypothesis of this proposal is if macrophages are eliminated in mice, immune modulation function of BMP-6 mediated by macrophages is abolished. Thus, role of macrophages on tumor growth in response to BMP-6 can be verified.



• Essential Role of Macrophages in the Host Response to Mycoplasma pneumoniae 
  Submitted by David Chaplin  (University of Alabama at Birmingham, Indian Springs, AL, United States) 4/21/2010
  After intranasal inoculation of mice with live Mycoplasma pneumoniae, the organism is eliminated from the host's respiratory tract over a 7 to 10 day period using exclusively innate immune mechanisms. Clearance is independent of lymphocytes, NK cells, NK-T cells, mast cells and neutrophils, but is impaired when macrophage numbers or function are reduced. This project will assess the mechanisms by which macrophages effect the clearance of this microbe from the lungs and airways.



• Anaphylaxis 
  Submitted by Lawrence Evans  (Amgen Inc., Seattle, United States) 4/21/2010
  Determine the impact of macrophage depletion on non-classical anaphylaxis.



• macrophage and brain injury recovery 
  Submitted by Hyunjung Min  (Seoul national university, Seoul, Korea, South) 4/21/2010
  We aim to distinct the specific role of each macrophage and microglia during recovery process in brain injury. Therefore, we try to deplete peripheral macrophage by clodronate liposome in intracerebral hemorrhage induced mouse and test the effect on recovery process.



• Humanized mice: an in vivo model to study Plasmodium falciparum malaria 
  Submitted by Anburaj Amaladoss   (Singapore MIT, Singapore, Singapore) 4/19/2010
  Mosue-human chimera will be used to study Plasmodium falciparum which are host specific and do not infect rodents



• The crossing of the endothelial barrier in the liver sinusoids by Plasmodium sporozoites  
  Submitted by Joana Tavares  (Institut Pasteur Paris, Paris, France) 4/14/2010
  To invade and develop inside hepatocytes, Plasmodium sporozoites must cross the liver sinusoidal barrier. The current view suggests that sporozoite uses Kupffer cells as a gateway to invade the hepatic parenchyma. We are dissecting the mechanisms used by the parasite to cross this barrier in the presence or absence of Kupffer cells.



• Role of macrophages in conditioning lesion response 
  Submitted by Richard Zigmond  (Case Western Reserve University, Cleveland OH, United States) 4/13/2010
  While the conditioning lesion response has been known for over 35 years, little is known about the cellular and molecular changes which trigger this interesting phenomenon. We have been studying the increased growth response which occurs in mouse sympathetic neurons one week after a conditioning lesion. We propose to determine whether the magnitude of this response is altered by reducing macrophage infiltration in response to the condtioning lesion. Mice will be injected with clodronate prior to and several times after a conditioning lesion. Sympathetic neurite outgrowth will then be examined in explant and/or dissociated cell cultures.