All our current ongoing projects have an unifying fundamental theme, i.e., unraveling the cell biological and molecular basis of multi-receptor signal gating by a novel class of molecules that we christened Rheostats. These rheostats can be utilized by all receptors during aberrant signal enhancement. The central theme is to help understand how rheostats can transduce signals downstream of diverse classes of receptors, and how dysregulated expression of these rheostats drive diseases that are multi-receptor in etiology and have no silver bullet therapies to tackle them. The ongoing projects in the lab can be divided into two broad categories-- "Purely Basic" that are aimed at understanding the nuts and bolts of molecular mechanisms that help rheostats operate downstream of multiple receptors and in various cellular processes, and those that are "basic with a strong translational component" that interrogate the validity of the hypothesis/findings in various disease models.
- Transcriptional regulation of rheostats
- Splicing-Mediated Regulation of rheostat functions
- Ubiquitination and proteasomal targeting as a method for regulation of rheostat functions
- Phosphoregulation of rheostats (inhibition and potentiation of known functions)
- Generation of rheostat-Biosensors (Fluorescent and cell permeable) to study rheostat function in cells.
- How rheostats and its various phosphomodifications can drive Cell Migration, Invasion and Cancer metastasis.
- Molecular basis for how rheostats can orchestrate Epithelial-Messenchymal Transition during cancer invasion, development and cellular stress response.
- Molecular basis for how rheostats regulate Cell cycle progression and signal transduction during cell division.
- Identification and characterization of an unique anatomical platform for receptor crosstalk (tyrosine kinases and GPCRs)
- G protein signaling and modulation of G protein activity by receptor tyrosine kinases during cell division and migration.
- Modulation of G protein signaling during cellular autophagy
- Drug designing: Targeting therapy to novel rheostats to modulate multi-receptor cellular signaling
- Crosstalk between energy sensing pathways and rheostats: maintenance of cellular polarity
Basic Science, with Strong Translational Component:
- Molecular basis for how rheostats and its various phosphomodifications can drive aberrant insulin response in Type II DM/Insulin resistance.
- Molecular basis for how rheostats and its various phosphomodifications can drive aberrant PI3K signaling in Alzheimers and Schizophrenia.
- Molecular basis for how rheostats and its various phosphomodifications can drive profibrogenic signaling in response to chronic injury of liver tissue.
- Role of rheostats in modulating of Wnt signaling in Ovarian cancers.
- How Rheostat expression can Serve as Biomarkers: Prognostication of colorectal and breast carcinomas
- How rheostat expression in circulating tumor cells and circulating stem cells in colon and breast cancet patients can serve as diagnostic and prognostic markers.
- Aberrant receptor signaling and signal amplification in response to cellular injury (epithelial wound healing/ intestinal ulcer healing)
- Rheostats as a target for immunomodulation: Macrophage response during infection