Atopic Dermatitis (AD) is a chronic, autoimmune dry skin disorder associated with impaired skin barrier permeability due to dysfunction of Filaggrin (FLG), protein and unknown triggering agents. In India, 2-9% of children and 2-4% of adults are affected by AD. Although multiple host genetic factors have been associated with AD, but only 14.4% of the total heritability of AD can be explained by th em. The missing heritability can probably be explained by other external factors. Skin is the largest organ of human body harbouring trillions of microorganisms that performs important functions. Studies have shown imbalance in microbiome (dysbiosis) to be associated with several chronic inflammatory diseases. However, how does the host genome modulate the composition and diversity of the resident skin microbiome is not well known. My research interest is focused on investigating the specific host-microbiome interactions which can explain the complex etiology of AD as well as mechanistic in vitro host cell-microbial co-culture experiments which might lead to cues for future therapeutic approaches. Read less
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Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is a form of Head and Neck Squamous cell carcinoma (HNSCC). Recent epidemiological studies reported – (i) India has one-third of all oral cancer cases in the world and (ii) oral cancer accounts for 30% of all cancers reported from India. Oral cancer is the topmost cancer among males in India and lin ked to tobacco chewing and smoking habits. Few driver genes were recently identified for late-stage OSCC-GB from genome-scale studies. Identification of early stage OSCC-GB biomarkers is of extreme importance, because it might potentially lead to precise understanding of the molecular mechanisms of tumor initiation, as well as the factors whose alteration might lead to progression of tumor. My research objective is to leverage state-of-the-art genomic technologies for understanding the profile of the genomic drivers of early stage OSCC-GB tumors. Deeper understanding of the molecular underpinnings of the alterations of these drivers will provide improved diagnosis, more precise risk prediction as well as better response to therapy.
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Diabetes affects almost 537 million people worldwide and 71 million people in India. Diabetic Foot Ulcers (DFUs) are a dreaded complication of Diabetes and 15-25% of diabetic patients run the risk of developing DFU in their lifetime. DFU infections are polymicrobial and bacterial biofilm formation in chronic wounds leads to persistent antibiotic resistance often resulting in limb amputation and d eath. Conventional culture-based methods cannot detect the viable but non-culturable (VBNCs) microbes. Massively parallel sequencing can identify both culturable and non-culturable microbes collectively termed as the microbiome. My research interest is to characterize (a) longitudinal shift in the composition and diversity of DFU microbiome both pre and post antibiotic treatment, (b) biofilm formation by confocal microscopy and (c) antibiotic resistance profiling of clinical isolates. Besides these, I will also identify host gene expression patterns in different cell types in chronic non-healing DFUs and integrate it with metagenomic as well as clinical factors to understand their contribution in impairment of wound healing. Read less
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Genome wide association studies (GWAS) are used to discover association of genetic variants with various complex diseases and traits. However, testing markers across the genome in an unbiased manner leads to loss of power for such studies. My research project deals with increasing the power of such genome wide studies by incorporating information from other sources. Knowledge from pathways, gene expression/eQTL studies and transcriptional regulation can be integrated with the information from GWAS to help in identifying variants that could be otherwise missed in an unbiased genome-wise search. My work emphasizes on building a pipeline for integrative statistical analysis of such multi-omics data. The pipeline will enable investigators to discover novel genetic variants and understand their mode of action, thus helping to elucidate the underlying genetic makeup of complex diseases.
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Human oral squamous cell carcinoma (OSCC) is the eighth most common cancer worldwide; and, the most prevalent cancer among men and fourth most common among women in India. Owing to the highly heterogeneous nature of oral carcinoma at both cellular and molecular levels, it is important to investigate the functions of altered pathways with respect to distinct cancer cell-types present wi thin the tumor as well as in its microenvironment. In the context of cell-cell interactions, NOTCH related signaling is intriguing because of its juxtacrine mode of action. Therefore, I am interested in studying the functional consequences of altered NOTCH related genes and its regulation within oral tumors. My focus is to examine the mechanisms of reciprocal interactions between diverse cell-types and its significance in oral cancer initiation and progression.
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I am Subhashree Jena, obtained my MSc from Annamalai University, Tamilnadu. As we know that heterogeneity in stem-like cancer cells significantly impacts cancer progression by contributing to adapt in different microenvironments, evade immune responses, and sustain tumor growth. These cells exhibit diverse molecular profiles due to variations in gene expression and signaling pathways. I am unders tanding the molecular mechanisms behind the emergence of diverse transcriptional states among stem-like cancer cells, in context to the diversity in morphogenetic signals in oral cancer. Read less
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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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Intratumor heterogeneity is among the greatest challenges in treatment of cancer. In spite of disruptive advances in sequencing technologies achieved over the last decade, high resolution comprehension of such heterogeneity has been beyond our reach until recently. Developments in high-throughput Single Cell RNA-Seq (SC-RNASEQ) may now enable us to dissect the diverse cellular populations o f tumors. In the future these technologies might inform the selection of targeted combination therapies and enrollment criteria for clinical trials. I am working on single cell RNA-Seq approaches to investigate the role of intratumour heterogeneity in tumour recurrence in Oral squamous cell carcinoma gingivo-buccal (OSCC-GB). My objective is to excavate the landscape of intratumor heterogeneity at single cell resolution and identify important clues on how cell type diversity relates to cancer recurrence.
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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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