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.
Read less Read MoreA number of GWAS studies conducted in 2009 on HCV (hepatitis C virus) showed that polymorphisms/variants in the interferon-lambda (IFNL) locus affect the HCV disease outcomes. Following this, in 2013, a new type III IFN, Interferon lambda-4 (IFN-λ4) was discovered. This gene is expressed due to the presence of the ΔG allele at the dinucleotide polymorphism rs368234815. Even though IFN-λ4 has p otent antiviral effects, its presence is associated with poor viral clearance in HCV-infected patients. Further studies have shown that polymorphisms, especially on IFNL4 and IFNL3, are intricately associated with many infectious and inflammatory diseases, such as fibrosis, COPD, asthma, thyroid, SLE, and certain cancers. Only a subset of individuals in our population (~>50% of Indians) can express a functional IFN-λ4. Even though strong association can be seen with IFNL4 polymorphisms with disease phenotypes in genetic studies, functional evidence for its role in such conditions has not been forthcoming. This has led to questions on the significance of IFN-λ4 in such studies at the same time favouring a role for the well-studied and more active IFN-λ3 in deciding some of the phenotypes. Healthy individuals can be good models to study the genetic and the consequent functional effects of IFN-λ3 or IFN-λ4 that may help us to understand the associated disease phenotypes better. I am interested in addressing the fundamental question of whether IFN-λ3 or IFN-λ4 or both could have functions in deciding the antiviral states in healthy individuals. I use an epidemiological study design to address this question. My work has the potential to decisively solve IFNL locus functional variant conundrum. Read less
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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.
Read less Read MoreChronic 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
Read MoreSepsis 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
Read MoreAnatomically 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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Period of gestation being an important determinant of infant’s health, adverse live birth outcomes are major public health concerns of global importance.Complications from preterm birth, which is defined as any live birth before 37 completed weeks of gestation, is the leading cause of mortality of children below 5 years. Interplay between environment and underlying genomics of both the mo ther and the fetus results in the preterm birth outcome. To combat the global health burden, early detection of the women having higher risk for delivering preterm is highly crucial which will help to provide personalized medical care to them. Since genomic markers have the potential to identify the high-risk women even to prior to pregnancy, so I intend to study the maternal genetic influences on preterm birth.
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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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Birth outcome is an important determinant of an infant’s survival and health even during adulthood. Identifying the complex physiological and molecular pathways involved in modulation of pregnancy outcomes is thus of paramount importance for understanding and developing strategies to reduce adverse birth outcomes like preterm birth (PTB). Genetic markers alone may not provide sufficient i nsights into these processes. Epidemiologic observations, mostly from neonatal genomes, suggest probable role of epigenetic disruptions in enhancement of risk of PTB. However, very limited information is available on the role of maternal epigenome in PTB till date. My goal is to study the temporal variations in maternal DNA methylation landscape that occur during pregnancy and identify those that are associated with adverse outcomes.
Read less Read MorePancreatic 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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