Characterization of the macrophage-derived regenerative signals in intestine

DESCRIPTION (provided by applicant): The candidate is Assistant Professor with considerable experience in studies of regenerative medicine and radiation biology. However, in order for the applicant to transition into a fully independent investigator, an additional supervisd training period is imperative. Dr. Guha who has mentored Dr. Saha on radiation induced normal tissue injury such as intestine will serve as mentor for current proposal. Dr. Jefferey Pollard has extensive research experience in the study of macrophage biology along with Dr. Timothy Wang pioneered in intestinal stem cell research will serve as an ideal co-mentors for this additional training. The research project will be primarily carried out in the department of Radiation Oncology and some part in developmental and molecular biology at the Albert Einstein College of Medicine which offers a scientifically motivating, collaborative and inspiring environment. Intestinal stem cell based research will be held in Dr. Wang's laboratory in Division of Digestive and Liver disease, Columbia University. The proposed five year career development plan is focused on: i) conferring upon the candidate a strong background in radiation injury, regenerative therapeutics and intestinal stem cell biology, ii) improving his research skills and fundamentals as well as the learning of new experimental approaches, iii) facilitating productive collaborations with established researchers and iv) developing his teaching, training, and group leadership skills. The main goal of the current research project is to characterize the macrophage derived Wnt ligands as regenerative signals by which macrophage regulates the intestinal homeostasis and induce the regeneration/repair process following intestinal injury. To test this hypothesis Dr. Saha proposed to use genetically engineered mice model to elucidate the role of macrophage derived Wnt to mitigate radiation induced intestinal injury. The studies are divided into three specific aims: 1.The identification of macrophages derived Wnt in intestinal regeneration following radiation injury. 2. The elucidation of the role chemokine receptor CCR2 in recruitment of circulating monocyte in irradiated intestine and mitigation of radiation injury. 3. Adoptive cell therapy with ex-vivo modulated autologous macrophage to induce Wnt secretion for intestinal injury.