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
Read More
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
Read More
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.
Read less Read More
Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide with a lowest 5-year survival rate ( < 5% ) and poor diagnosis among other cancers. This intractable malignancy is often caused by some genetic alterations and also by pancreatic damage due to recurrent bouts of inflammation of chronic pancreatitis. In recent years, several regulatory functions of long non-coding RNAs (lncRNAs) have come to picture which were initially considered to be junk elements of the genome with no function. Role of lncRNAs in various types of cancer has been gradually revealed and in the case of pancreatic cancer also, intricate role of lncRNAs have been uncovered with implications in cell cycle, apoptosis, autophagy, epithelial-mesenchymal transition (EMT), metastasis and immune responses. But still there are several important lncRNAs which have significantly altered expression in pancreatic cancer and their functions are yet to unfold. Aim of my research project is to functionally characterize few such lncRNAs in pancreatic carcinogenesis and also to find out if they have any role in progression of pancreatitis to pancreatic cancer. Read less
Read More
Pregnancy is a complex physiological process associated with successive changes in the uterine environment that facilitates childbirth. The period of gestation varies from 37-42 weeks in Term Birth and < 37 weeks in Preterm Birth (PTB). Globally, PTB is one of the leading cause of child mortality and morbidity. Many preterm survivors face a lifetime of disability, including respiratory, learn ing, visual disability and the number of premature babies is increasing exponentially with time. Identification of the complex aetiologies behind premature delivery is a big challenge worldwide. The vagina plays an important role in childbirth and is also home to a population of facultative and obligate anaerobic microorganisms that maintains the hygiene and pH of the vaginal milieu. This polymicrobial community is difficult to characterise through conventional microbiological culture based methods and are collectively termed as the Vaginal Microbiome. Recently, the role of oral as well as placental microbiome in preterm birth has also gained much interest. I am interested to investigate the change in composition and diversity of the Maternal Microbiome associated with Preterm birth in India. A multi-omics approach will be undertaken to dissect the host-microbiome interactions between host factors and differentially enriched microbial gene families as well as functional pathways that ultimately lead to Preterm Birth. Read less
Read More
Maternal-fetal interactions play a major role during pregnancy. The optimal growth of the developing fetus and healthy birth depends on the nourishment it obtains during the gestational period. Placenta is the temporary feto-maternal organ that serves as a connective link between mother and fetus during pregnancy and is the hub of maternal-fetal dynamic interactions. This complex organ is made up of heterogeneous cell types which have diverse morphologies and dynamic functions at different time points during pregnancy. My aim is to study the variations in these cell type diversity and materno-fetal interactions at different periods of gestation at delivery using single cell transcriptomic approaches. Ultimately, I would like to identify single cell gene expression signatures which are associated with adverse outcomes. Such information can be used to triage women at risk of these birth outcomes so that appropriate clinical interventions can be used. Read less
Read More
Oral cancer is a major health burden in India, with high incidence rates driven by tobacco use and betel quid chewing, leading to late-stage diagnoses and poor survival outcomes. My research focuses on understanding how genomic and epigenomic alterations, such as DNA methylation aberrations, mutations, and copy number variations, influence immune cell infiltration in head and neck squamous cell c arcinoma (HNSCC), particularly in oral cavity tumors. By analyzing these molecular changes, we aim to decipher their impact on tumor progression, immune response, and patient survival. This knowledge can help stratify patients into risk groups and enhance prognostic models, ultimately guiding personalized therapeutic strategies for better clinical outcomes. Read less
Read More
Brief description of the project: Pancreatic cancer is the seventh leading cause of cancer related death globally. Late detection is one of the major obstacles for pancreatic cancer diagnosis. Metastasis is a very common phenomenon of pancreatic cancer with most people having advanced pancreatic cancer at the time of diagnosis. Metastatic pancreatic cancer is aggressive with poor prognosis. Epith elial mesenchymal transition (EMT) is a critical driver of metastasis that allow tumour cells to migrate, invade and colonize new sites. Recent studies show that TGF-beta can induce EMT. lncRNAs which were initially considered as junk element, in recent years they have been found to play important roles in different types of metastatic cancers, with their role to promote EMT and metastasis. Aim of my research project is to find out deregulated lncRNAs in TGF-beta induced cellular model of pancreatic cancer and also to explore functional involvement of selected lncRNA in pancreatic cancer metastasis. Read less
Read More
I am Priyanshi Sisodia, integrated MSc-PhD student of NIBMG. Despite advancements in therapies, the major challenge in treating patients with oral cancer is loco-regional metastasis and recurrence. Tumor-stroma crosstalk is one of the non-cell autonomous factors that drives plasticity in cancer cells eventually leads to recurrence of more aggressive tumor. Among the diverse components of regulato rs, long non-coding RNAs (lncRNAs) have emerged critical for gene regulation and cellular plasticity. My study focuses on understanding how tumor microenvironment induced lncRNAs contribute to oral cancer progression. Read less
Read More
In recent years, astrocytic dysfunction has garnered considerable attention in neurodegeneration in Alzheimer’s disease (AD) research. Connexin 43 (Cx43) is the major astroglial gap junction (GJ) protein. Cx43 hexamers constitute hemichannels and head-on docking of hemichannels of two apposed cells forms gap junctions (GJs). While GJs are of paramount importance for maintenance of panglial netw ork communication in central nervous system, providing trophic support to neurons and forming conduits for synaptic informational processing, increased Cx43 hemichannel activity leads to excitotoxicity. Interestingly, Aβ, the bonafide player of AD triggers Cx43 internalization in astrocytes with concomitant loss of gap junctional activity and increase in hemichannel activity. At this juncture, our study is directed towards understanding the Aβ-mediated astrocytic dysfunction process through gaining profound insights into the mechanistic underpinnings of Aβ mediated dysregulation of Cx43 gap junctional functions and how it contributes to AD neuropathology. Read less
Read More
