Dr. Payal Mittal

Dr. Payal Mittal
Post-doctoral Fellow, UConn Health School of Medicine, USA


Optimizing Dual costimulation mediated immunotherapy by including tumor unrelated CD4 T cell help During my postdoctoral training I have been working on an NIH-supported research project aimed at uncovering how dual costimulation (DCo) of the T cell costimulatory receptors OX40 (CD134) plus 4-1BB (CD137) programs cytotoxic CD4+ Th1 cells and how these effector T cells can be harnessed to suppress tumor growth. I have shown that inclusion of tumor-unrelated CD4 T cell help greatly boosted the ability of DCo to control established tumor growth through the classical linked pathway as well as through non-linked help that facilitates CTL function in Tcells that were not directly responding to cognate antigen (Mittal P. et al, 2015; J Immunol). I am currently working on another sub aim of the project that is looking at transcription factors involved in programming the cytotoxic CD4+ Th1 cells, as well as in their direct cytotoxic activity against MHC class II+ tumors and/or their ability to provide tumor-unrelated help. My results have shown that the transcription factor Runx3 regulates eomesodermin transcription factor, and helps drive tumoricidal activity in DCo-treated CD4+ T Cells. The manuscript describing this work is currently under preparation. Developing a novel metastatic cancer mouse model by dysregulating G protein coupled receptors My second project focused on generating novel transgenic mouse model that we predict to develop aggressive form of prostate cancer resulted from dysregulation of G protein-couple receptor signalling in prostate epithelium. I have already established several founder lines and at least few lines when crossed with TRAMP transgenic mouse line develop substantially larger and more metastatic prostate tumors as compared to TRAMP single trangenics. Ph.D-Work: Studies on Mycobacterial Polyphosphate Kinases During my PhD studies, I investigated the structural, functional, catalytic, and kinetic details of mycobacterial polyphosphate kinase (PPK) 1, an enzyme required for mycobacteria survival under stress conditions and thus a promising therapeutic target. I showed for the first time that differential activities of polyphosphate kinase 1 are regulated by distinct residues within the active site (Mittal P. et al, 2011; PLoS One). Furthermore, in contrast to the earlier reports regarding the functional necessity of involvement of the head domain in PPK1 dimerization, we providedthefirstevidenceimplicatinginvolvementofthecatalyticdomain in the enzyme?s dimerization. Work as Research Assistant: Development of sustained release drug delivery system of PLG. Nanoparticles against experimental Tuberculosis Tuberculosis is among the top 10 causes of global mortality. In general chemotherapy of tuberculosis requires the intake of anti-TB drugs daily a period of 8-10 months. Hence, patient non-compliance is one of the major hindrances associated with the cure of tuberculosis. Therefore, the current emphasis now is on the development of new drug carrier systems for effective drug delivery of anti-tubercular drugs. Polymeric devices have been extensively investigated as drug delivery tools besides numerous other biomedical applications. An ideal drug delivery system aims to control the rate and /or site of drug release so that the drug bioavailability is maximized. Numerous natural polymers are available. The use of synthetic polymers like polyesters of hydroxy acids i.e. polylactide, poly (lactide-co-glycolide) was already demonstrated. I therefore, developed a strategy to formulate the PLGA nanoparticles based encapsulation of front line as well as second line anti-tubercular drugs (ATDs) and checking the resultant formulations for their effect on the reduction of toxicity, improvement of bioavailability and efficacy against experimental tuberculosis.

Research Interest

Tumor, G protein coupled receptors, Nanotechnolgy