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New Research Funding from National Tea Research Foundation to identify PKC agonist from Tea.

 

RESEARCH @ MRG

 

Anti-malarial Drug Discovery

Currently we have focused on two pathways in malaria parasite to design antimalarial agents; Intracellular signaling molecules such as protein kinases and Proteases. We have screened heterocyclic compound library, drug library, plant phytochemicals and molecules designed using ligand-based approach, to identify potent antimalarial agents (Eur Food Res Technol, 234: 905-911, Curr Drug Discov Technol, 10, 85-91, Med Chem Res, 22; 4737-4744, Eur J Med Chem, 70, 607-612.). The best molecules from the search are found to exhibit anti-malarial activity against plasmodium falciparum 3D7. Now we are taking these molecules and checking their activity in mice and other animal models. In addition, these molecules are serving as the first line of molecules to design potent anti-malarial agents.

 

 

 

Drug Target

Immunotoxcity studies in Macrophages

Malaria infected blood is rich in pro-oxidant molecules such as hemin, hemozoin, hemoglobin, methemoglobin and malarial toxins. These pro-oxidant molecules are cyto-toxic towards different types of cell types. In this research project we are interested to study the effects of these pro-oxidant molecules towards macrophages and various mechanisms through which macrophage could be able to recover from toxic effect of pro-oxdiant molecules especially hemin. The role of macrophage in protection against malaria as well as their role in host pathology.

RD project

Regulation of Innate Immune Response.

Phagocytic cells such as monocytes,macrophages and neutrophils are essentially plays a crucial role in innate immune response and all are involved in phagocytosis of IRBCs. Macrophage  often use pattern recognition receptors, including Scavenger receptor to recognize as well as phagocytose invading microbes. Out of them CD36,plays a pivotal role in non-opsonic phagocytosis of P.falciparum infected RBCs. Here our current focus is to understand the crucial signaling mechanism behind CD36 desregulation and its impact on cytokine secretion during malaria.

 

 

CD 36 Model

EC-RBC cytoadherence during Cerebral Malaria

In this project we are studying the role of pro-oxidant molecules and their effect on cyoadherence of RBCs towards brain endothelium, Vascular coagulation and RBC aggregation.

Host Factors are known to support parasite growth (such as hemoglobin) either directly to provide an excellent source of nutrition or helps parasite to manage the metabloic waster such as hemin, free radicals etc. In addition, host factors may induce intracellular signaling in infected RBCs and that may in-turn activate parasite cellulart machinaery for higher growth, more round of invasion etc.

Designing immunostimulatory and Anticancer agents.

Protein kinase C is a family of serine/threonine kinases that plays a central role in cellular signal transduction in mammalian physiology such as growth, differentiation, tumor promotion and apoptosis. Diacylglycerols(DAGs) serve as endogenous ligands in healthy cells. The PKC isozymes have important roles in tumor biology. Elevated levels of PKC are seen in proliferative cancer cells compared to healthy cells like immune cells. Recent studies suggest that PKC signaling is crucial for immune-activation of neutrophils and lymphocytes.

Our goal is to discover new lead molecules for a new generation of chemotherapeutic drugs that act via activation of PKC isozymes in healthy immune cells leading their activation to induce proper immune response. In addition, these molecules may activate PKC in cancer cells leading to their apoptosis. Also we would want to have a picture of the various possible apoptotic signaling pathways activated by such agonist molecules by interaction with their respective PKC isozymes in cancer cells.

PKC project

MRG LAB FUNDING