Research Projects

Identification and classification of extracellular vesicles (EVs) released from biological cells into the extracellular space is one of the key challenge in the field of cell biology. Although EV research has evolved and stolen the limelight in recent years, its biogenesis, the functional mechanism of biomolecular packing load, exocytosis, and interaction with the host cells are still undefined. Particularly, the role of tumor EVs in cancer pathogenesis has not been identified as tumor cells produce more EVs than normal cells. Among EVs, exosomes are the predominant small extracellular delivery vehicles that have proteins, lipids, metabolites, DNA, and microRNA signals for secret communications in the body. Without understanding the biology and functions of EVs, researchers have already started exploiting these exosomes as drug carriers in various biomedical diseases including cancer therapy. There is a huge paucity of data on its biological understanding like, a) Are all cell-bound vesicles released from the cells are EVs? b) Why are all EVs not packed with biomolecules? c) What is the crosstalk in EV–cell communication in pathogenesis? d) What is the functional role of EV load in recipient cells? e) What is the fate of the EV after delivery? Thus, understanding the functional role of extracellular communications between cancer cells and their surrounding stromal cells is imperative to delineate its immunosurveillance escape and pathogenesis mechanism. Particularly, exosomes from tumor cells often mislead or shut down nearby immune cells by transferring secret messages. Its cellular package is believed to be modulated by the state and stimuli of the cells, but no clear mechanism has been identified on their programmed packing. There is a huge paucity of data on its biophysical properties in terms of its bio-molecule loading pattern. This proposal aims to investigate the programmed cellular packaging mechanism of functional biomolecules in exosomes during normal cell cycle regulation in comparison with the tumorigenic phase of the cells. Further, this proposal will test the hypothesis that the tumor cells selectively package immunosuppressors and metastatic growth factors. For this, a multi-omics approach on the biomolecule packaging load of tumor exosomes under different stages of metastatic cell progression will be investigated, along with the in-depth functional analysis on its interaction with immune-host cells for cell-exosome communication, antigen presentation, and pathological transfer mechanisms. As the outcome, with a translational focus, the cellular biomolecular packing mechanism of exosomes can be reprogrammed with bioengineering approaches for personalized tumor therapy.