Research
Pushing the Boundaries of Scientific Exploration
Hypoxia-mediated expansion of transcriptome due to epigenetic modifications in breast cancer tumorigenesis and chemoresistance
Hypoxia-induced response plays a key role in the progression of Triple-negative breast cancer (TNBC) and is considered as one of the hallmarks of TNBC. Hypoxia promotes an adaptive transcription response resulting in epigenetic changes which support cancer cell growth. The epigenetic modifications are known to regulate alternative splicing, which is an emerging hallmark of cancer. However, the interplay between hypoxia and alternative splicing is largely unexplored in TNBC. Here, we want to investigate whether and how hypoxia contributes to the generation of cancer-specific spliced isoforms via epigenetic modifications and whether hypoxia-induced alternative splicing is involved in the tumorigenesis of TNBC.
Role of deregulated epigenetic modifier in oral cancer
Several studies have identified a change in epigenetic marks such as DNA methylation, histone modification, alterations in nucleosome remodeling, differential expression of miRNA, as well as altered expression of chromatin-modifying proteins in oral cancer. These epigenetic changes may lead to alteration in global gene expression pattern, which may attribute to the development and progression of oral cancers. Most of the studies focusing on epigenetic-based biomarkers have identified changes in DNA methylation, post-translational modifications of histones and miRNA pattern as biomarkers. However, chromatin-associated proteins which may contribute to these epigenetic changes have been largely ignored. Hence, we are investigating the deregulated expression of epigenetic modifiers in oral cancer. This study will help us in understanding the role of epigenetic events in cellular transformation and these epigenetic modifiers may serve as the markers for early-stage detection and prognosis of oral cancer.
DNA methylation mediated regulation of PKM alternative splicing
Alternative splicing process can generate multiple protein coding isoforms and is the major source of transcriptome and proteome diversity. Aberrant spliced isoforms has been implicated in various cancers. Similarly deregulation of epigenetic modifications is also associated in the development and progression of many cancers. Here, our focus is to study the role of DNA methylation and DNA binding proteins in the regulation of PKM alternative splicing in breast cancer.
Alternative splicing and Epigenetics regulating autophagy in breast cancer
Autophagy is a self-regulatory catabolic process that maintains cellular integrity and concomitantly eradicates toxic molecules such as intracellular pathogens, misfolded proteins, cancerous molecules, and damaged organelles including mitochondria, endoplasmic reticulum, and peroxisomes. Cancer cells indeed have evolved by exploiting the autophagy process to fulfill energy requirements and to escape stressful conditions. In that context, the role of autophagy in cancer is subjected to intense investigation, and the work in this field has been extensively explored in the past several years. Thereupon, biological factors regulating autophagy provide new insight into modulating cancer progression.
Investigating the role of Exosomes in Glioblastoma progression
Exosomes are small (~30-100nm) extracellular vesicles (EVs), that are derived from multivesicular endosomes and are known to contain a variety of bioactive molecules such as DNA, mRNA, miRNA, lncRNA, proteins, and lipids. They serve as a powerful mechanism of intercellular communication and are being widely studied due to their potential application in tumor diagnosis and therapy. Glioblastoma is the most common primary CNS tumor, and is characterized by its aggressive and malignant nature. We are interested in investigating the role of exosomes in glioblastoma progression.
Nutraceuticals mediated the effect of epigenetics in the restoration of normal isoform from cancer-specific splicing isoform in oral cancer.
Nutraceuticals are natural products with nutrient value, reported to affect epigenetic modifiers, and have substantial therapeutic effects on cancer. In this study, we investigate the use of epigenetic-based therapeutic compounds with minimal toxicity and side effects (nutraceuticals) on cancer-specific alternative spliced isoform.