Research Projects

Calpains are calcium activated cysteine proteases that regulate their activity by concentrations of cytosolic calcium. They play a role in influencing processes such as cytoskeletal rearrangement, membrane permeability, and mitochondrial functions. Calpains are considered modulatory proteases and can alter the activity or localization of proteins. However, their role in the pathophysiology and progression of Uterine Corpus Endometrial Carcinoma (UCEC) remains largely unknown. UCEC is the fourth most common gynaecological malignancy in developed countries and the second most common in developing countries. A study showed that the enhanced expression of calpstatin, an endogenous inhibitor of calpains, in endometrial tissues from patients with endometrial cancers. Recently, mutations in 11 cancer types were near predicted calpain cleavage sites using Deepcalpain, leading to Calpain Cleavage Related Mutations (CCRM) and CCRM proteins. Most of these mutations are predicted to alter calpain cleavage sites, potentially changing the calpain regulatory network. The proposed study aims to characterize the interaction of calpains with CCRM proteins and its relevance to the progression of UCEC. A protein network analysis will be used to identify key proteins essential for cancer progression and metastasis. The best docked complexes will be validated using molecular dynamic simulation studies and in vitro protein protein interaction studies. N-terminal sequencing of cleaved fragments will reveal the cleavage sites in each protein, which will be matched with predicted CCRMs. This study will broaden our understanding of calpain mediated processing of cancer proteome and offer novel strategies for developing therapeutic interventions.