Research
Latest Research
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Decoding ncRNAs as Diagnostic, Prognostic and Therapeutic markers/tools for Human Cancers
It is now believed that rncRNAs, such as miRNAs, lncRNAs and piRNAs are promising rheostats of gene regulation as they target a significant .... fraction of genes in a genome. The dysregulation of these rncRNAs are associated with cellular dysfunctions leading to diseases, such as cancers, neurodegenerative diseases and many more. Moreover, some of these rncRNAs are reported to function as oncogenes or tumor suppressor genes.
Seeing the differential characteristic expression patterns of mRNAs as well as rncRNAs in carcinomas, such as breast cancer and ovarian cancer (two major female cancers), we propose that the interplay between genes/mRNAs and epigenetic events (DNA hyper/hypo- methylation and histone modifications) or genes/mRNAs and rncRNAs (miRNAs/piRNAs) might be playing a major role in the initiation and metastatic spread of these females malignancies. Breast cancer is the most commonly diagnosed cancer in women, whereas ovarian cancer is less common, but the fifth most lethal cancer in women as it’s symptoms are obscure which make it much harder to detect this gynaecological cancer. Seeing the lethality of these cancers, our lab is focussed to identify genomic and epigenomic hub operating in these two female malignancies to bridge the gap of understanding of regulation at molecular level with an aim to develop rncRNA-based therapeutics and diagnostic markers for these two cancers. Investigations are underway to decrypt the roles of rncRNAs and epigenetic events (hyper/hypo- methylation) in understanding the oncogenetic/metastatic events in these two malignancies by integrating expression profiling and analysis, next-generation sequencing, target analysis (reporter assays), methylation studies (bisulfite sequencing) and inhibition/over-expression studies in cell lines to identify potential rncRNA-biomarkers, especially piRNA biomarkers and predict key epigenome–rncRNA-mRNA regulatory circuits responsible for malignant growth or metastasis which in turn might help in diagnosis and treatment of these female cancers. -
piRNAs and other ncRNAs surmounting Chemoresistance in Cancer
Several GWAS studies have reported single nucleotide polymorphisms (SNPs) or INDELs to be associated with susceptibility of diseases, .... such as cancer (breast cancer, ovarian cancer) as well as neurodegenerative diseases (Parkinson’s disease, Alzheimer’s disease). The underlying mechanisms of disease associations are generally explained for non-synonymous SNPs present within coding regions of the genes. However, roles of SNPs that are present elsewhere (5’UTR, 3’UTR) in the genome, but found to be associated with these diseases remain largely unknown. It is well known that miRNAs target mostly 3’UTR and rarely 5’UTR of mRNAs through complementary base pairing with 2-7/8 nts of miRNA and regulate expression of corresponding target mRNAs. Therefore, mutations/SNPs reported in 3’UTR and 5’UTR of the genes associated with above diseases might lead to creation of new target sites or destruction of target sites for miRNAs differentially expressed in these diseases. This will help in understanding aetiology of diseases through impact of SNPs located elsewhere in the genome other than coding regions. Two parallel studies are on-going in our lab to decipher miRNA-mediated regulations interfered by the presence of SNPs and their functional consequence in cancers (breast cancer, ovarian cancer) and neurodegenerative diseases.
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Drug repurposing using signature miRNAs to find new drug(s) for endometriosis-associated infertility and other diseases
Besides malignancies, miRNAs have been found to have critical roles in self-renewal, pluripotency and differentiation of embryonic stem cells (ESCs). ... fraction of genes in a genome. The dysregulation of these rncRNAs are associated with cellular dysfunctions leading to diseases, such as cancers, neurodegenerative diseases and many more. Moreover, some of these rncRNAs are reported to function as oncogenes or tumor suppressor genes.
Seeing the differential characteristic expression patterns of mRNAs as well as rncRNAs in carcinomas, such as breast cancer and ovarian cancer (two major female cancers), we propose that the interplay between genes/mRNAs and epigenetic events (DNA hyper/hypo- methylation and histone modifications) or genes/mRNAs and rncRNAs (miRNAs/piRNAs) might be playing a major role in the initiation and metastatic spread of these females malignancies. Breast cancer is the most commonly diagnosed cancer in women, whereas ovarian cancer is less common, but the fifth most lethal cancer in women as it’s symptoms are obscure which make it much harder to detect this gynaecological cancer. Seeing the lethality of these cancers, our lab is focussed to identify genomic and epigenomic hub operating in these two female malignancies to bridge the gap of understanding of regulation at molecular level with an aim to develop rncRNA-based therapeutics and diagnostic markers for these two cancers. Investigations are underway to decrypt the roles of rncRNAs and epigenetic events (hyper/hypo- methylation) in understanding the oncogenetic/metastatic events in these two malignancies by integrating expression profiling and analysis, next-generation sequencing, target analysis (reporter assays), methylation studies (bisulfite sequencing) and inhibition/over-expression studies in cell lines to identify potential rncRNA-biomarkers, especially piRNA biomarkers and predict key epigenome–rncRNA-mRNA regulatory circuits responsible for malignant growth or metastasis which in turn might help in diagnosis and treatment of these female cancers. -
Dissecting the route of spread of cancer
Metastasis is another major challenge that limit the cancer therapy. The rates and routes of spread of cancer are poorly understood owing to a lack of molecularly characterized patient cohorts, lack of correlation between clinical features of primary and secondary cancer, .... and lack of correlation between genomic features, such as differential expression of ncRNAs, and target genes in primary and secondary tumor. We propose to decrypt signature ncRNAs that dictate the susceptibility of a cancer to develop a secondary cancer, its route and site of developing secondary tumor. We propose to use high-throughput methodologies, expression profiles from relevant NGS studies, clinical features of tumor and develop a model that will help to understand how the cancer cells spread from the primary site to the secondary site through the process of metastasis.
Funding Research Support
Title: Gomutra ark as a potent anti-cancer agent for the treatment of oral squamous cell carcinoma- Molecular mechanisms underlying its anti-cancer effect
Funding Source: Ayush
Role: Principal Investigator
Title: Identification of new drug(s) for treating Endometriosis-associated Infertility by drug repurposing using signature MicroRNAs
Funding Source: ICMR
Role: Principal Investigator
Title: Genome-wide profiling of PIWI-interacting RNAs (piRNAs) by Next-Generation Sequencing and investigating their role in Oral Squamous Cell Carcinoma
Funding Source: DBT
Role: Principal Investigator
Title: SNP mediated changes in the structure of VPS26A mRNA and its implication in the aetiology of Diabetes.
Funding Source: ICMR
Role: Co-Principal Investigator
Title: Integration Polymorphisms and NGS in dissecting complex networks of mi RNA-mediated regulation in neurodegenerative diseases
Funding Source: DST
Role: Principal Investigator
Title: Identification of piRNA associated genomic and epigenomic regulatory networks in ovarian cancer
Funding Source: DST
Role: Mentor
Title: Decoding the Dominant microRNA-mediated Pluripotency Networks in Stem Cells
Funding Source: CSIR
Role: Principal Investigator
Title: Investigation on seaweed based synbiotic formulation for combating malnutrition in Sundargarh District of Odisha
Funding Source: DST
Role: Mentor
Title: Structural impact of SNPs on miRNA-mediated regulation and its implication in Cancer
Funding Source: DBT
Role: Principal Investigator