It is very much intriguing to understand and explore how a eukaryotic cell uses a set of rules in distributing various macromolecules to their target destination in a temporally regulated fashion. A large set of molecular machineries function under stringent spatial and temporal regulation to safeguard these rules. Sometimes, these rules are violated which results into pathophysiological situations.

Theme I:

The invasion and metastasis are one of the hallmarks of cancer and major reason for mortality among cancer patients. A series of events take place, leading to dissemination of the tumor growing in a confined area to metastasize and spread in multiple organs resulting in multi-organ failure. Once cancer reaches the invasive stage, the disease becomes much more challenging to treat and live-threatening. Breast cancer is among invasive tumors that show metastasis in the lymph node, lung, brain, and liver. Cancer invasion is attained by degrading extracellular matrix (ECM) components and breaching basement membrane. Matrix metalloproteases (MMP) are reported to have a broad range of enzymatic activity towards ECM components and their role in promoting tumor invasion is well established in the field. The membrane type metalloproteases such as MT1-MMP (MMP14) and MT2-MMP (MMP15) are over-expressed in triple negative breast cancer (TNBC) tumor cells corroborating with their invasiveness. Additionally, they also render non-proteolytic functions such as activating soluble MMPs: MMP2, MMP13, and many cell adhesion and signaling receptors. MT2-MMP degrades E-cadherin leading to the onset of EMT (epithelial to mesenchymal transition), a key step that activates cellular invasion. The intracellular localization and cell surface transport of these MT-MMPs is crucial for modulating their enzymatic activity and other functions.

Theme II:

The pathogenic amoeba, E. histolytca is one of the causatve agents for health hazard in tropical countries. It causes amoebic dysentery, liver abscess in human. About 50 million cases of amebiasis and 40-100 thousands cases of deaths are reported annually. Even though inexpensive treatment is readily available for amebiasis the frequent recurrence occurs because of lack of proper preventive knowledge and poor sanitary system. This makes amebiasis one of the major burdens on the health systems in developing countries. Recent studies from our and other laboratories have highlighted the functions and importance of several amoebic Rab GTPases in pathogenicity of the parasite. A follow-up proteomic study has provided several downstream amoebic proteins which help the parasite in its pathogenicity. Current goal of the lab includes investigating the molecular mechanism underlying cytoskeletal rearrangement by these newly identified molecules.