Sourav Ghosh

Our laboratory investigates signal transduction pathways. We are broadly interested in the functional characterization of signal transduction pathways during development and in diseases.

Polarity signaling pathway: We are interested in the signal transduction pathways that regulate cell polarity. Polarity or asymmetry of protein distribution within cells is a fundamental biological property. Many aspects of cell biology such as, asymmetric stem cell division and differentiation, and directional cell migration rely on proper polarity signaling. Our research has characterized the function of a protein kinase – atypical Protein Kinase C or aPKC – in cell adhesion and apical-basal polarity in neural stem/progenitor cells during development [2]. Current research is focused on the comprehensive understanding of the role of aPKC signaling during organogenesis, and its altered function in tumorigenesis and invasion.

TAM family of receptor tyrosine kinases: A tightly regulated inflammatory response is essential for the protection against pathogens. Notwithstanding, unchecked or overzealous inflammation can favor the development of chronic inflammatory and autoimmune diseases. Chronic inflammation, such as in Inflammatory Bowel Disease (IBD), increases the risk of cancer. Our laboratory is investigating TAM signaling components in inflammatory diseases [3].

Telomere Independent Rap1 Is An Ikk Adaptor And Regulates Nf Kappa B Dependent Gene Expression. Source: Nature Cell Biology
July 11th, 2010 PMID: 20622870 Sourav Ghosh
We describe a genome-wide gain-of-function screen for regulators of NF-kappaB, and identify Rap1 (Trf2IP), as an essential modulator of NF-kappaB-mediated pathways. NF-kappaB is induced by ectopic expression of Rap1, whereas its activity is inhibited by Rap1 depletion. In addition to localizing on telomeres, mammalian Rap1 forms a complex with IKKs (IkappaB kinases), and is crucial for the ability of IKKs to be recruited to, and phosphorylate, the p65 subunit of NF-kappaB to make it transcriptionally competent. Rap1-mutant mice display defective NF-kappaB activation and are resistant to endotoxic shock. Furthermore, levels of Rap1 are positively regulated by NF-kappaB, and human breast cancers with NF-kappaB hyperactivity show elevated levels of cytoplasmic Rap1. Similar to inhibiting NF-kappaB, knockdown of Rap1 sensitizes breast cancer cells to apoptosis. These results identify the first cytoplasmic role of Rap1 and provide a mechanism through which it regulates an important signalling cascade in mammals, independent of its ability to regulate telomere function.<br><br>
Anharmonic Interaction Signals For Acoustic Detection Of Analyte. Source: Analytical Chemistry
April 30th, 2010 PMID: 20384294 Sourav Ghosh
The challenges with frequency-based acoustic detection systems in sensitive, selective, and reliable quantitative estimation of surface-bound analyte are well-known. These systems are traditionally used in their linear incarnations; i.e., the measurement frequency is the same as the driving frequency. However, it was found in this work that interactions of adsorbents with sensor surface show significant anharmonicity even at low drive amplitudes. In particular, using streptavidin-coated polystyrene microbeads on an oscillating quartz surface in air, it has been demonstrated through modeling and experiments that the anharmonic signal from microparticle to surface interaction is significantly higher relative to that from bare quartz and orders of magnitude higher than relative shifts in resonant frequency. The signal is proportional to the number of microparticles and holds a well-defined functional relationship with the amplitude of oscillation, distinct to the nature of interaction with the surface for a given analyte. This approach, thus, can be used for ultrasensitive and quantitative detection of surface adsorbents and characterization of different kinds of surface interactions, distinguishing specific from nonspecific adsorbents. The modeling also reveals a direct functional relationship between the measured anharmonic signal and the interaction potential of the adsorbent with the surface.<br><br>
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