Chronic Obstructive pulmonary disease (COPD) is a multifactorial disease characterised by irreversible airway obstruction and progressive deterioration of pulmonary function. COPD is the fifth leading cause of mortality worldwide affecting 251 million lives globally. The disease is characterised by airflow obstruction and inflammation that gives rise to the clinical symptoms. Genetic component an d particulate matters play significant role in COPD progression. Environmental triggers like cigarette smoke, pollen grains, carbon black nanoparticles, dust particles, microbial infection etc. are responsible for COPD exacerbations. NLRP3 inflammasome, a cardinal component of the innate immune system plays significant role in regulating the lung pathophysiology during exacerbations. The aim of my research is to examine the molecular pathway of NLRP3 inflammasome activation, identify the genetic factors associated with the disease in an unexplored heterogenic prototype study of Indian population and design intervention strategies using stem cells and genetically modified T cells. Read less
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Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, accounting for one-fifth of all deaths globally. Many children and adults who have bacterial sepsis develop abnormal coagulation in the intravascular compartment thus impeding oxygen supply to the organs. I am interested in the cellular and molecular underpinning of abnormal coagulation in blood of p atients admitted to intensive care unit (ICU). I am focusing on the phenomenon called Neutrophil extracellular trap (NET), that is produced by neutrophil in response to pathogen. NETs consist primarily of decondensed chromatin of neutrophils and can trigger immune-thrombosis. The study shall have three components: computational (integrated analysis of multi-cohort transcriptomic data), clinical (collection of blood samples from neonates admitted to ICU with sepsis) and experimental (investigation of the molecules that trigger NET formation). Read less
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Anatomically Modern Humans (AMH) originated in Africa around 150,000-190,000 YBP (Years Before Present) and started moving Out of Africa (OoA) about 50,000-100,000 YBP. Following the OoA event, AMH underwent several demographic transitions, e.g., population bottlenecks, population expansion, population split, genetic drift, and evolutionary forces of natural selection in the journey of peopling t he globe. The constant interaction between genotype(G) and environment(E) resulted in the local adaptation of human populations with phenotypic trait differences across populations. Thus, spatially structured populations and spatially varying phenotypic traits provide an opportunity to study the environmental factors which might have acted as selective forces for human populations to adapt to their local environment. My research work focuses on the development of deep learning architecture for modeling genotype-environment interactions to detect genomic regions under natural selection in different human populations. Read less
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Healthy pregnancy outcomes are critical determinants of public health. Preterm birth (PTB), remains the leading cause of neonatal morbidity and mortality. The etiology of PTB is multifactorial, involving complex interactions between genetic, environmental, and physiological factors. The mechanisms by which genomic variants, identified in the genome-wide studies, influence the risk of preterm birt h remain largely unknown. One potential mechanism involves the regulation of gene expression through alterations in DNA methylation at specific CpG sites. My research aims to investigate the role of these genetic variants in modulating biological processes implicated in PTB, with a particular focus on their effects on DNA methylation and cell types of the placenta where these genes are differentially expressed. Thus, this will not only explain how these variants modulate the risk of PTB, but also delineate biological pathways involved in this birth outcome, ultimately providing valuable insights for developing targeted therapeutic interventions Read less
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Research in the last decade has shown that the genetic background for pancreatic cancer, especially pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic tumours. PDAC has poor prognosis and a rising incidence rate. Late detection and threatening nature are two major causes for treatment failure. In case of treatment, identification of some biomarker molecules helps in proper diagnosis. It has been found that some specific genes accelerate cancer progression rate in multiple pathways. There are some specific genes which act as biomarkers, affecting cell cycle regulation, cell signalling mechanisms etc. My research goal is the functional characterization of specified genes which act as progression biomarker and their interaction with other molecules that help retaining cellular proliferation in pancreatic cancer.
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Pancreatic Ductal Adenocarcinoma (PDAC), the most frequent form of pancreatic cancer, is one of the major causes of cancer-related deaths worldwide. This is an aggressive and devastating cancer with a five-year survival rate of less than 9%, the lowest among common cancers. CP (Chronic Pancreatitis) is one of the major reasons to proceed toward PDAC. The mis-regulation during chronic pancreatitis may induce several epigenetic changes. The consequence of such epigenetic modification in pancreatic cancer is not known completely yet. Moreover, a reliable epigenetic feature of active enhancers is the production of enhancer-directed transcripts (eRNAs). eRNAs are tightly regulated and play important roles in gene regulation, which was previously considered as junk element inside the cell with no function. My interest is to explore the role of eRNA in PDAC and how does eRNA regulate the progression of Chronic Pancreatitis to Pancreatic Cancer. Read less
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Primary angle closure glaucoma(PACG) is a major subtype of glaucoma and its prevalence is higher among South Asians including Indians. My research interest is to investigate the functional role of genomic signatures associated with PACG and related quantitative traits. In a previous case-control GWAS from our lab, TNF-α promoter SNP rs1800629 is found to be associated with PACG in Indian patient s. Interestingly it is already identified to be associated with different glaucoma subtypes across various populations worldwide reporting either G or A as risk allele. Investigating the underlying mechanism of rs1800629 will help in revealing its involvement with neurodegeneration and neuroprotection. In another Quantitative Trait (QT) GWAS on lens thickness we reported the novel association of PTPRM genic region. My research is focused on the functional characterization of PTPRM and understanding the underlying molecular mechanisms. It will facilitate a better understanding of risk factor and disease pathophysiology. Read less
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I am a RCB-GSK fellow working in the area of biostatistics and statistical genomics. In genomic studies of complex diseases, one typically quantifies the importance of genomic features and their interactions by analyzing them individually (e.g. individual genes or variants or pathways) or in some cases as pairs of features (e.g. gene-gene interaction). However, to estimate overall risk of disease accounting for all features in the genome and interactions, analyzing one gene at a time (marginal modeling) is not adequate. Further such marginal modeling cannot assess the causal contribution of a risk factor accounting for all other factors and interactions. My research objective is to develop a high-dimensional joint model of genomic risk factors (accounting for interactions), which is both biologically interpretable and computationally tractable at the whole-genome level. Disease risk prediction being the central theme, my work involves applying various statistical and machine learning techniques in large-scale phenotype and genotype data from UK Biobank and other consortia. Read less
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Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral cavity cancers and is a major cause of cancer mortality globally. Growing evidence suggests that the tumour ecosystem shares mechanisms and effectors with embryogenesis and is of central importance for tumorigenesis. Our earlier work has indicated that some malignant cells are expressing genes specific to fetal development, de scribed as oncofetal reprogramming. However, fetal genes expression in different malignant cell states and their function in oncofetal reprogramming in OSCC tumour ecosystem, is not yet delineated. My objective is to investigate the role of oncofetal genes of malignant cell states in cancer cell proliferation, migration and immune evasion in OSCC. Such information can facilitate in early patient stratification and differential clinical management. Read less
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Sepsis is a dysregulated host response to an infection. Often caused by antibiotic-resistant bacteria, it results in hospitalization and poor outcome, and accounts for nearly 20% of all global deaths annually. The outcome of an infection depends on pathogen-factors such as virulence and antimicrobial resistance as well as host-factors such as the immune and inflammatory responses. My aim is to undertake a comprehensive study of K. pneumoniae-mediated sepsis by dissecting the pathogen-associated molecular characteristics that impinge upon host immuno-inflammatory response and evaluating its susceptibility to antimicrobial therapy. I am also looking to examine genes in clinical isolates of K. pneumoniae involved in perpetuating virulence and resistance and investigate the transcriptome of human neutrophil exposed to certain factors associated with pathogenesis. Optimization of a suitable antimicrobial-combination therapy against K. pneumoniae is another important goal of my work.
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