Current Research Interests

TGF-beta biology, with emphasis on its tumor promoting roles; Cancer biology including breast, oral and brain cancers; molecular targets and functional genomics of Precancerous lesion, oral submucous fibrosis.

Currently, the laboratory is focused on the regulation of gene expression particularly by growth factors and hormones in disease processes. Using micro arrays, the differential regulation of genes by TGF-beta in normal and tumor cells has been demonstrated and mechanism of regulation of some of the TGF-beta targets such as S100A2 has been deduced. S100A2 gene is involved in tumorigenesis and experiments conducted in our laboratory revealed its pro tumorigenic role especially for invasion and growth of the tumors. TGF-beta regulates several pro tumorigenic genes in transformed cells and not in normal cells. This differential expression of genes may require oncogenic transformation and MAPK pathway activation. It is not clear as to which pathway triggered by oncogenic transformation is responsible for pro tumorigenic actions of TGF-beta. TGF-beta and its family members Activins are involved in the tumor invasion/metastasis. The precise mechanisms are being studied.

In the cancer biomarker identification, significant contributions have been made in the area of novel biomarkers for prognostic and therapeutic use in gliomas and breast cancers. The expression and role of IGFBP isoforms 2, 3 and 4 in glioma progression/prognosis has been studied. Expression of IGFBP2, 3 and 4 were found to correlate with poor prognosis in GBM patients and promote the invasiveness of tumor cells. IGFBP2 is also associated with high grade breast cancers and functional studies suggested its role in invasion and EMT. Finally, as a part of efforts to study cancer initiation, work on molecular characterization of a pre cancerous lesion called submucous fibrosis is carried out. A molecular connection between the arecoline actions on epithelial cells, fibroblasts activation has been deduced. This together is instrumental in the initiation and progression of submucous fibrosis. TGF-beta and BMP7 pathways were found to play important but opposing roles in the progression of OSF.

Our laboratory also contributed significantly to the area of chemical biology especially the search for anti cancer molecules. Recent discoveries include, identification of a small molecule that activates mutant p53.
In the future, the emphasis would be on the functional characterization and study the role of genes that are identified as differentially expressed in OSMF, novel differentially expressed genes in glioma and breast cancer tissues, biology of tumor metastatasis, characterization of anti cancer activities of small synthetic molecules.

Ongoing Projects