3D cell culture platforms for tumor engineering, biomarker discovery and drug assaying
We are developing 3-dimensional (3D) cell culture matrices of tunable physical and biochemical properties, akin to that of native tissue so that experimental manipulations can occur in a physiological context. Since these models can realistically represent the metastatic condition, they could be used to understand the role of cellular and non-cellular components of tissue microenvironment in cancer progression. This might help elucidate cell-cell and cell-stroma crosstalk pathways active during disease progression which could be potential therapeutic targets.
Eventually, we hope to fine tune these culture systems to function as reproducible drug screening platforms to help design more effective therapeutics. Further, these matrices could be tweaked to support growth of primary tumor cells which could then be used to assay therapy response or predict metastatic potential.
We are working with breast cancer as a model to develop these culture systems since it is the most common malignancy in women worldwide. In India, 5-year survival rates for breast cancer remain less than 50%. Moreover, certain conditions like Triple Negative and Metastatic Breast Cancer are unmet clinical needs, with limited treatment options.
Nanotechnology platforms for cancer therapeutics
The advancement of nanotechnology offers a new dimension to tumor-targeting strategies. We are interested in developing smart delivery system for anticancer drugs, i.e. multifunctional nanoplatforms comprising biocompatible polymers, anticancer drug and cancer specific ligands that can efficiently resolve the in vivo stability versus intracellular drug release problem, as well as stealth versus tumor cell uptake issues. This involves, but is not limited to, fabrication of polymeric nanoparticles, effective drug encapsulation, controlled drug release, functionalization with cancer cell specific ligands (surface modification) for specific targeting and to achieve enhanced therapeutic efficacy of drugs without systemic toxicity. This work is being done in collaboration with the Nanomedicine research group.
RNAi-based platforms for targeted therapy
Broad spectrum and standard therapeutic agents fail to target leukemia initiating cells (LIC). It is now believed that relapse originates from LIC-containing minimal residual disease (MRD) and the frequency of relapse correlates with the burden of LIC resistant to conventional chemotherapy. Therefore, targeted therapies that eradicate LIC and complement current regimens are needed. miRNA have recently been shown to play a role in malignant transformation and leukemia. We would like to identify miRNA that have been deregulated in different subtypes of leukemia, understand how miRNA trigger LIC-mediated MRD following chemotherapy and ultimately develop systems for effective delivery of RNAi therapeutics.
Tissue-engineered platforms for biomedical applications
Mesenchymal Stem Cells (MSC) are multi-potent stromal cells that can differentiate into a variety of cell types and thus help maintain tissue homeostasis following injury or inflammation. We are interested in engineering culture environments that will allow us to modulate this pluripotency of MSC and direct their differentiation, enabling clinical use of such `Tissue Engineered Constructs’.