Neurodegeneration often is a consequence of accumulation of misfolded aggregated proteins in different areas of the brain that further leads to cell death and inflammation. This aggregation is mainly attributed to defects in the protein clearance system, predominantly in the endo-lysosomal pathway. Normal functioning of the endo-lysosomal pathway is critical in maintaining cellular homeostasis. S everal neurodegenerative diseases like Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Frontotemporal dementia (FTD), etc have been found to be caused as a result of a defective endo-lysosomal pathway. These perturbations in the functioning of the endo-lysosomal pathway are known to occur long before the occurrence of disease phenotype. My research aims at finding genetic variations and novel prognostic genomic markers in regions of increased homozygosity that are specific to the Indian population within the genes involved in the endo-lysosomal pathway. I will also be exploring the mechanistic role of TMEM106B, a lysosomal transmembrane protein that is associated with risk of numerous neurodegenerative conditions. Read less
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Oral squamous cell carcinoma (OSCC) is a major cancer type globally and the most common form of cancer in men in India. Oral submucous fibrosis (OSMF) is one of the most prevalent chronic, disabling condition of the oral mucosa and 7-30% of OSMF cases can lead to malignancy in the oral cavity. The transition from pre-malignant lesions and disorders to OSCC is a continuous process of genetic a nd histologic modifications that lead to malignant transformation which is yet to be delineated. Although much data on oral cancers have been generated by bulk genomic studies, the transcriptomic triggers of this progress from OSMF to OSCC is yet to be established. I am working on single cell RNA-sequencing to gain insights into the entire tumour ecology, including intratumoral and intertumoral heterogeneity, as well as cellular interactions that may play a critical role in in this process. Such information can facilitate early triaging of OSMF cases at risk of malignancy and hence reduce occurrences of OSCC. Read less
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Fatty liver disease among the non-alcoholic individuals or NAFLD is the most common chronic liver disease. Initial stage of the NAFLD is benign i.e., simple steatosis but when it progresses to advanced stages such as NASH or cirrhosis it may lead to hepatocellular carcinoma. NAFLD is a heterogenous disease - age, sex, ethnicity, environmental factor, genetic, epigenetics, metabolic health and mic robiota all are dynamically interact with each other and orchestrate disease progression. It is considered as hepatic manifestation of metabolic syndrome and is associated with the risk factors - obesity, T2DM and dyslipidaemia. Imbalance in the intake of calorie and its utilization can lead to ectopic fat accumulation in the liver. What are the exact differences in between NAFLD individuals and the fatty liver individuals with metabolic dysregulation unclear yet. My research is focused on the study the bidirectional interplay between fatty liver and metabolic alteration. Read less
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Chronic pancreatitis (CP) is an irreversible disease characterized by progressive inflammation, fibrosis of pancreas, and loss of pancreatic functions. Epidemiological studies have identified CP to be a major risk factor for pancreatic ductal adenocarcinoma (PDAC). PDAC is one of the most lethal diseases with an incidence rate almost equal to the rate of mortality. Elucidation of the molecu lar mechanism driving the development of the diseases will not only help us understanding the disease biology but also help us identifying key molecules which could be used as potential biomarkers for early detection of the malignant disease. Regulation of gene expression by epigenetic mechanisms has gained much importance due to their important role in disease pathophysiology and my work revolves around delineating the role of key epigenetic factors in the development of chronic pancreatitis and pancreatic ductal adenocarcinoma.
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Nonalcoholic fatty liver disease (NAFLD) is a complex disorder. Both genetic and environmental factors affect disease pathogenesis. NAFLD begins with aberrant accumulation of triglycerides in the liver which is called hepatic steatosis. In some individuals it can lead to inflammatory responses and causes progression to Nonalcoholic steatohepatitis to cirrhosis, and subsequently hepatocellul ar carcinoma. The pathogenicity of the disease is poorly understood and therapeutic options are very limited. My work emphasizes on understanding the molecular mechanisms and the role of related pathways involved in disease progression from mild to advanced stages and validation of the role of some specific genes associated with NAFLD in the Indian population in in vitro and in vivo models.
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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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Complex human diseases arise from interactions among genetic variation, regulatory networks, and environmental factors across multiple molecular layers. My PhD research focuses on developing scalable computational frameworks and R-based analytical pipelines for integrating large-scale genomic, transcriptomic, and epigenomic datasets to identify genes and biological processes driving complex trait s. The key objectives include building efficient data infrastructures for high-dimensional multi-omics data and developing statistical modules for GWAS–QTL integration and cross-tissue regulatory mapping to move from genetic association to causal inference. This work aims to characterize the genomic architecture of complex traits and enable deeper understanding of disease mechanisms. 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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