Noscapine Research Lab

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Our research interests are primarily focused on the chemoprevention, and treatment of pre-cancerous and cancerous diseases that arise from misregulation of the highly orchestrated mitotic process, using a chemical-genetic approach. The biological system that forms the core of our research is the ubiquitous polymer, microtubule, that plays a central role in the life of a cell. More recently, microtubules are emerging as pharmaceutically validated targets for a number of clinically important drugs effective against a variety of disease states. The currently available armamentarium of tubulin-binding drugs primarily relies on two major classes-the taxane family (represented by paclitaxel, docetaxel- that overpolymerize and bundle microtubules) and the vincas (typified by vinblastine, vincristine, vinfluinine- that depolymerize microtubules and form paracrystals). Although they are widely used in the clinic, owing to their extreme gross effects on microtubules, these drugs cause various debilitating toxicities (such as peripheral neuropathies, gastrointestinal toxicity, myelosuppression, alopecia) and wreak havoc on the patients’ bodies. Thus, the over-arching focus of our research is to identify a class of ‘kinder and gentler’ anticancer molecules that dampen microtubule dynamics just enough to engage the mitotic checkpoints to halt mitoses but leave other processes such as axonal transport relatively intact. This would, perhaps, ameliorate most of the toxicity issues and would be a major breakthrough in anticancer drugs that are not only efficacious but are non-toxic and thus do not compromise the quality of life. 

One of the major research thrusts in our lab is to investigate the anti-angiogenic potential of a novel microtubule-modulating anticancer agent, EM011 and we are currently focusing on establishing the link between the dampening of microtubule dynamics by this agent and inhibition of tumor angiogenesis via the HIF-1 pathway. The unique non-toxic attributes of our drug present us with an exclusive opportunity to reduce the dose levels of more toxic drugs by combination therapy in order to maximize therapeutic efficacy and the quality of life by minimizing chemotherapy-associated toxicities. Along these lines, we are employing combinatorial regimens of ‘biologically-effective’ doses of independently-acting drugs to maximize therapeutic responses with minimal toxicity. We are also examining potential synergism between tubulin-binding agents that do not share the same binding site on tubulin. 

Our research strategies encompass synthetic chemistry for chemical manipulations based upon molecular docking studies and rational drug-design, in vitro cell biology to gain mechanistic insights of drug action at the cellular and molecular level, in vivo models to study kinetics of tumor growth/inhibition, evaluation of pharmacokinetic profiles of drugs, etc. Towards these goals, we are continuing to investigate the unique family of small-molecule anticancer agents based upon the novel plant-alkaloid noscapine, which is already in Phase I/II clinical trials. 

The experimental strategies utilize several techniques in cell and molecular biology including in vitro cell proliferation and apoptotic assays immunofluorescence, confocal microscopy, live-cell confocal imaging, flow cytometric analysis, immunoblotting techniques, non-invasive bioluminescent animal imaging, immunohistochemical analysis, bioanalytical HPLC method development and drug extractions from plasma samples for pharmacokinetic analysis.