Our group investigates the characteristic and functional make up of the Mononuclear Phagocyte System (MPS), hence Dendritic cells (DC) and Macrophages (MF), in the Gastrointestinal tract, adipose tissue and in the liver in health and disease. Among our research interests:
The liver Mononuclear Phagocyte System in health and disease
The liver is being increasingly recognized as playing a central role in the immune response, being pivotal in maintenance of peripheral tolerance in homeostatic conditions, and induction of inflammation upon encounter of potentially harmful pathogens or chemical danger signals. The liver is densely populated with innate immune components, and in particular the mononuclear phagocyte system (MPS). The main research aim of our group is to study the in-vivo cellular and molecular functions of liver-MPS in homeostasis maintenance and establishment of disease
The Intestinal Mononuclear Phagocyte System in health and disease
The intestinal tract is the "wild west" of the human body, covering an area of approximately 100 m2, and is lined by a single layer of columnar epithelial cells that forms the barrier between the host connective tissue and the gut lumen, which is constantly exposed to the microbiota as well as dietary and environmental antigens,. It is in this unique, complex and vulnerable setting that inflammatory bowel diseases (IBDs), such as Crohn’s disease and Ulcerative Colitis, occur in genetically predisposed individuals. The intestinal immune system is delicately balanced between active tolerance towards the commensal microbiota and food antigens and the induction of robust responses to pathogens. Maintenance of this critical balance is attributed to the mucosal-MPS. In the recent years pioneering studies including ours have shed light on our comprehension of the intestinal-MPS ontogeny and function. Currently, we are conducting a big scale expression microarray in which we compare between the distinct intestinal lamina propria MP subsets under homeostatic conditions and inflammatory settings. These results will be aligned with MP subsets isolated from human intestinal tissue of IBD and colorectal cancer patients (in collaboration with Prof. Steffen Jung, Weizmann Inst'). This research avenue may constitute the base for future cell specific therapy of IBD.
Colorectal cancer (CRC) research has profited much from the availability of murine models, however, these models often suffer from prolonged windows of establishment, poor reproducibility and adverse side effects. The recent technical advance in in vivo mouse endoscopy now allows for repetitive high-resolution evaluation of the colon in living mice. Utilizing this system in our research center we have developed a method for sub-mucosal orthotopic induction of CRC. This minimal invasive technique is highly repetitive, quick, circumvents the side effects associated with other murine CRC models, is highly controllable, and allows for the side-by side comparison of adjacent genetically distinct tumors within the same mouse. Importantly, utilizing this system we can also monitor tumor growth and take biopsies. We currently use this method to study: (1) Studying the role of the intestinal MPS in CRC development (in collaboration with Prof. Steffen Jung, Weizmann Inst') (2) Development of a targeted nanomedicine to treat CRC (in collaboration with Dr. Dan Peer, Tel-Aviv Uni').