Research Interest

Glioma is a general term used to depict primary brain tumors, which is classified into astrocytic tumors, oligodendrogliomas, ependymomas, mixed gliomas (Eric C. Holland,2000). Glioblastoma is the most common as well as the malignant type of primary astrocytic tumor (Fumiharu Ohka et al.,2012). Even though there are various therapeutic strategies available to treat glioma, it remains one of the deadliest diseases with an abysmal prognosis, and very low survival rate (K Rock et al.,2012). In the course of the most recent decade, a scope of various medicines was examined with restricted achievement. Standard therapeutic strategies for glioma have improved survival of glioma patients, however, the tumor-associated macrophages (TAMs) are responsible for poor prognosis which interacts with various cells present in the tumor microenvironment and helps in tumor growth, angiogenesis, metastasis, thereby suppressing responses to existing glioma therapeutics (Fei Teng et al.,2016). Hence, it has become very significant to target these TAMs to suppress tumor progression. Most of the TAM population are M2-type macrophages or anti-inflammatory in nature. In high-grade glioma, there is evidence of extensive cross-talk between TAM and glioma cells. This cross-talk mutually influences both TAM and glioma cells to promote the aggressiveness and progression of glioma (Dolores Hambardzumyan et al.,2016). Novel strategies are constantly being developed to target the TAM in glioma using immunotherapies and immune checkpoint blockers (Dipongkor Saha et al.,2017). However, the exact signaling mechanism in the glioma microenvironment(GME) is poorly understood, and the exact polarization process of TAM is unknown. Hence, extensive study is required on macrophage polarization in glioma to enhance the effectiveness of standard therapeutics and the development of novel strategies for targeting glioma. One of the major cells of innate immunity, macrophages are present in all tissues and known for their phagocytic ability, antigen presentation capability and they exhibit a continuum of dynamic states in the presence of external stimuli. Hence, modulating macrophages to the desired state in a particular tissue or organ can be utilized in order to develop novel therapeutic strategies to treat autoimmune diseases as well as various cancers like glioma. Studies have reported CECR1(Cat eye syndrome critical region protein 1), a regulator of TAM polarization is highly overexpressed in GME, which helps in paracrine stimulation-mediated glial cell growth & survival through Ki67, MAPK pathway (Changbin et al.,2017). It has also been found to interact with pericytes, eventually helping in neovascularization in malignant glioma through PDGFB-PDGFβ signaling ( C Zhu et al., 2017). Thus, the objective of my work is to stop the macrophage polarization in GME by targetting this novel CECR1 protein with potent inhibitors to stop cancer progression in glioma patients.