Trophic role of macrophages to rescue intestinal stem cell from radiation injury during cancer therapy.
Intestinal injury is a limiting factor for definitive chemo-radiation therapy of abdominal malignancies, such as, gastric, pancreatic and colorectal cancer. Thus, tumoricidal doses of RT or chemotherapy are not administered in the treatment of abdominal tumors, resulting in poor survival and early metastatic spread. Intestinal injury limits the application of high dose stereotactic radiosurgery (SRS) in abdominal cancers. Using novel mice genetics and virus-based tool Dr. Saha's group has already demonstrated that macrophage/myeloid population in intestinal stem cell niche is critical for intestinal epithelial homeostasis. Currently his lab is involved to determine the macrophage derived regenerative signal and specific phenotype of macrophages involved in intestinal repair following radiation injury.
Macrophages in colonic inflammation and malignancy
Pro-inflammatory macrophages promote the onset of malignancy by inducing stress-adaptive responses of the inflamed epithelium as well as cellular survival and self-renewal. The anti-inflammatory/tissue resident macrophages are primarily involved in invasion and metastasis. Dr. Saha's group is pursuing another project to determine origin, phenotype and mechanism of invasion of these macrophages in irradiated tumor tissue. Overall goal of this project is to develop candidate agents which can deplete these pro-malignant macrophages or modulate their recruitment to induce the radio-sensitivity of tumor tissue.