Sharmila Sengupta

Biography

1991 Calcutta University Ph.D 1982 Saha Institute of Nuclear Physics/ Calcutta University Post M.Sc. 1981 Utkal University M.Sc 1979 Utkal University B.Sc

Research Interest

Understanding the natural history of HPV infection and cervical cancer development among Indian women Epidemiological studies have established a causal relationship between HPV infections and occurrence of cervical cancer (CaCx). It is observed that (i) CaCx incidence rates and (ii) prevalence of HPV infections at the population level are variable across the country. My research aims to gain insight into HPV incidence, prevalence, type distribution, persistence (in longitudinal follow-up of cohorts of women) in various regions of West Bengal and north-eastern States of India. This would be coupled with a genomics based approach to decipher the genetic underpinnings of the two known crucial stages in the natural history of cervical cancer – (i) viral persistence (population based) and (ii) progression to pre-cancer/cancer (hospital based). Interrogating the intricacies of host pathogen interactions in HPV related cervical cancer pathogenesis through a genomics based approach Recent functional studies have revealed that natural genetic variation modulates risks to common diseases including infectious diseases, through gene expression, that provides a link between the DNA sequence and the phenotypes that characterize clinical disease. Thus, quantification of transcript abundance could be used to provide insights into causal genomic underpinnings of diseases. Such differences in gene expressions have been correlated with the genetic variations in the cis and trans regulatory sequences/factors in populations. Epigenetic alterations on the other hand, including DNA methylation, histone modification and RNA mediated gene silencing, afford a level of transcriptional regulation above and beyond DNA sequence. The focus of my research is therefore to explore the association of coding and noncoding transcription (miRNA and long non-coding RNAs), uncharacterized transcripts and their function on gene regulation, genome control and their correlation with genetic variations in CaCx pathogenesis. Molecular reasons why HPV infection is controlled in some women or instead progresses to subsequent stages of tumorigenesis are largely unknown. Methylation of cytosine residues at CpGs within promoters (at CpG Islands) loss of genome-wide methylation and the degree of hypomethylation have been observed in some cancers to be associated with tumorigenesis. The aim of my study is also to test the hypothesis that epigenetic changes (CpG methylation) in HPV16 and host genomes are crucial for the development of HPV16 related CaCx among Indian women and jointly influence disease risk by modulating the expression of key viral genes and host genes of relevant cellular pathways. HPV16 E2 gene disruption, as a consequence of viral integration into the host genome, mediates the loss of negative feedback control of viral oncogene expression and hence is a critical event in cervical carcinogenesis. Interestingly, in many HPV-induced CaCx cases, we find the existence of intact E2 genes or lack of evidence of the canonical pathway of HPV-induced transformation. That is suggestive of the existence of alternative pathway(s) by which HPV induces cellular transformation in these CaCx cases. We therefore hypothesize that the genetic/epigenetic make-up of an individual could likely influence the mechanism by which HPV induces cellular transformation in cervical epithelial cells. Therefore, it becomes essential to focus on the elucidation of various mechanisms adopted by HPV16 in mediating cervical carcinogenesis, employing a genomics based approach followed up by functional assays to get insights into the molecular mechanisms of disease development., which could also lead to biomarker and therapeutic target development.