Congenital muscular dystrophy and myopathy belong to a group of rare neuromuscular disorders. A common subtype of these heterogeneous disorders caused by mutations in nuclear proteins is Emery-Dreifuss muscular dystrophy (EDMD). Mutation in emerin (EMD) causes X-linked EDMD and autosomal dominant EDMD is caused due to mutations in muscle specific nuclear envelop transmemebrane proteins - lamin A (LMNA), nesprin1, nesprin2, SUN1 and FHL1. Using whole exome sequencing in Indian patients, a number of mutations in EMD and LMNA were reported from our lab. My research is focused on functional characterization of these mutants in vivo in both human skeletal muscle cells and in zebrafish which would provide a better insight of heterogeneity in EDMD pathogenesis. Further, by understanding the process of myogenesis in human skeletal muscle myoblasts, I would like to investigate the interplay among various molecular players in background of EMD and LMNA mutants towards progression of EDMD pathogenesis. Read less
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Understanding the genomics of health and wellbeing is essential for unravelling of genomic underpinnings of diseases. Expression quantitative trait loci (eQTLs) are known to play an important role in the various biological processes which determine health. However, analysis of eQTLs in gene expression data from bulk tissues is challenging due to the use of average gene expression across multiple cell types as input for eQTL mapping. In recent years, single-cell RNA sequencing has led to the understanding that each cell type has unique gene expression signatures and cell state. Elucidation of the role of eQTLs in defining the healthy state can be achieved by using single-cell-based studies of the immune cells. My interest is to investigate the role of genomic variations in regulating cell-type-specific gene expression in peripheral blood immune cells which may provide important insights into blood immunity and thereby our health and wellbeing. Read less
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Developmental glaucoma spectrum disorders include conditions such as aniridia, Axenfeld-Rieger syndrome, Peter's anomaly and primary congenital glaucoma that severely affect the eye anterior segment along with the retina and optic nerve. Ten genes were found mutated in a cohort of patients having this disease spectrum. Bioinformatic analyses indicated possible interactions between two mutated gen es; WT1 and MMP9 and further in silico investigation suggested presence of putative WT1 binding site on MMP9 promoter. WT1, being a transcription factor is known for its promiscuity, acting as both activator and repressor of transcription in various tissue types. Interestingly, WT1 is also in close genomic proximity with another transcription factor, PAX6, which is reportedly a master regulator of eye anterior segment development. We are currently doing reverse genetics in zebrafish along with other molecular biology techniques to elucidate any underlying interactions and possible role of these transcription factors in developmental glaucoma spectrum disorders. Read less
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What makes cancer the ‘Emperor of all maladies’? Each tumour is unique in terms of the somatic alterations they carry. Moreover, within the same tumour different cancer clones carry distinct somatic alterations. Such widespread intra-tumour heterogeneity (ITH) makes patient prognosis challenging. To add to this complexity, the cancer cells do not exist in isolation, as the surrounding immune cells and cancer-associated fibroblasts play a crucial response in dictating the evolutionary trajectories of the tumour. My research focuses on untangling how the genetic and non-genetic heterogeneity drives tumour-progression and patient-prognosis. Our lab has previously characterised the genomic-landscape of oral cancers and highlighted the frequent co-occurrence of multiple driver-gene mutations within the same tumor. By investigating the diverse Darwinian-evolutionary patterns of oral tumors, I aim to elucidate how ITH influences clinical outcomes in oral-cancers. To address my research objectives, I perform integrative-analysis of multi-omics high-throughput data using statistical and computational frameworks. Read less
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I am Uday Saha, integrated MSc-PhD student of NIBMG. Since, tumor microenvironment (TME) plays crucial role in driving metabolic plasticity and contribute significantly to tumor progression and aggressiveness. To meet increased energy and biosynthetic demands, cancer cells uptake the secreted metabolites from stromal cells such as lactate, glutamine, and fatty acids. My study focuses on the mecha nistic understanding of how distinct subtypes of cancer associated fibroblasts in oral cancer regulate the metabolic pathways in cancer cells, enhancing cellular plasticity on stemness and EMT axis. Read less
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Humans originated in Africa and migrated across the globe, adapting to diverse climates, diets, and environments. My research in evolutionary biology focuses on how natural selection has shaped the genetic architecture of adaptive traits by integrating genomic and climate data. I am also passionate about understanding the impact of climate on disease epidemiology and studying human genetic divers ity to uncover patterns in disease susceptibility, historical social behaviors, and the evolutionary forces that have shaped our genomes. Read less
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