0364 2307930 - 2336
9774566179
srimoyee@nehu.ac.in
srimoyee2009@gmail.com
Designation: Professor
Department: Zoology
Ph.D. (2002)
Dept. of Zoology, University of Calcutta, India.
Title of thesis: Interacting alleles affecting chromatin in the polytene X-chromosome of Drosophila melanogaster and polymorphism at the level of DNA and proteins involved therein.
M.Sc. (1991)
Dept. of Zoology, University of Calcutta, India.
Subject: Zoology; specialization in Advanced Cytology & Genetics.
B.Sc. (1989)
Dept. of Zoology, Jogamaya Devi College, university of Calcutta, India
Subject: Zoology (Honors), Botany and Chemistry.
Other exams qualified:
Postdoctoral Research Experience:
Pre-doctoral Research Experience:
| 2005-2009 | Postdoctoral Fellowship: Genomic sites of developmental and tissue specific DNA methylation |
| 2004-2005 | Postdoctoral Fellowship: Methylation profiling in cervical and breast cancers |
| 2003-2004 | Postdoctoral Fellowship: Characterization of modifiers of Polyglutamine diseases in Drosophila models |
| 2000-2003 | Postdoctoral Fellowship: Drosophila models of human neurodegenerative diseases |
| 1997-1998 | Research Fellowship: Polymorphism at the level of DNA and protein as genetic marker in response to heavy metal stress, insecticides, detergents and crude oil surfactants |
| 1993-1996 | Junior Research Fellowship: Position effect variegation (PEV) as a system to expose genomic domains that are involved in the control of PEV, homeotic pathway, developmental regulations and retrotransposons insertional mutations in D. melanogaster |
| 1992 | Graduate Aptitude Test for Engineering (GATE): conducted by Indian Institute of Technology, India. 89.33 percentile |
Publication and Citation Summary (Google Scholar):
| Total publications | 21 |
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Citations |
1084 |
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h-index |
14 |
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i-index |
15 |
Extramural projects:
| Sl | Title | Funding agency | Period | Amount | Role in project |
| 1 | Identification and development of DNA methylation biomarkers for oral/oropharyngeal cancers prevalent in the North-Eastern states of India | DBT, GOI | August 2013 to August 2017 | Rs. 53,08,000.00 | PI |
| 2 | Identification and development of DNA methylation biomarkers for stomach cancers prevalent in Mizoram, India | DST, GOI | December 2013 to December 2016 | Rs. 46,54,000.00 | PI |
| 3 | Identification of Biomarkers of oropharyngeal cancer prevalent in North-Eastern states of India by whole genome Methylation and Expression profiling | DBT (NER) GOI | December 2014 to July 2018 | Rs. 85,20,000.00 |
PI |
Peer reviewed:
Abstracts:
Expertise in research techniques:
Molecular Biology:Southern hybridization including RFLP, sub-cloning, PCR including RAPD, in situ hybridization: radioactive and non-radioactive, site-directed mutagenesis, RNA isolation and gene expression assay, gene silencing by siRNAs
Methylation Analyses: Restriction Length Genomic Scanning (RLGS), Bisulfite sequencing, Methylation Specific PCR (MSP), MethyLight assay (Q-MSP), primer designing and data analyses for methylation study using MALDI-TOF MS assay from Sequenom, MeDIP assay for CpGi and promoter array analyses, knowledge of Combined Bisulfite Restriction Analysis (COBRA)
Protein Chemistry: 2-D gel electrophoresis of proteins, in vitro protein expression and interaction, western blotting, isozyme analysis
Fly Techniques: Micro-injection of Drosophila embryo, immunohistochemistry of Drosophila brain sections, P-mediated mutagenesis & enhancer-trap technique in Drosophila, Drosophila genetics including fine structure analysis, autoradiography of Drosophila polytene chromosomes
Tissue/Cell culture: Mammalian cell culture, Drosophila cell culture
Postdoctoral Associate: Roswell Park Cancer Institute, Buffalo, NY
2004-2009
Topics of research: Profiling Methylation in cancer and normal tissues
Labs of Dr. Hiroki Nagase and Dr. William Held (Oct 2005-present):
There is considerable evidence, which show that the susceptibility to cancer development in humans involves the same processes as those seen in mouse. Besides genetic variations, epigenetic modifications, most importantly DNA methylation, plays a role in human cancer development and risk. We wanted to probe this event by using the two-stage mouse skin carcinogenesis model. Using the technique of Restriction Landmark Genomic Scanning (RLGS) with the enzyme combinationNotI-EcoRV-HinfI to globally scan the genome for methylation events associated with skin cancer in mouse, we have compiled a list of genes that are methylated and call them skin tumor-specific differences in methylation (ST-DMRs). We have confirmed some of this methylation data by methylation specific MassArray technique (MALDI-TOF MS system from Sequenom). We also performed whole genome expression analyses using Agilent arrays to identify the correlation between expression and DNA methylation at some ST-DMR. We also used CGH BAC array analyses of these cancer samples and found a correlation between BAC loss and DNA methylation at the same locus for a candidate gene. We are presently analyzing the functional role of candidate genes, which are located near the ST-DMRs, using skin cancer cell lines. Since most of the ST-DMRs are conserved between mouse and humans, we are choosing some orthologous regions of these ST-DMRs and elucidating their methylation status in some human cancers (melanoma, colon and lung cancer). This work furthers our understanding of how DNA methylation status impacts on each step of tumor development. It could also identify potentially new pathways of tumorigenesis. We are also performing methylated DNA immunoprecipitation (MeDIP) assay of multipotent mammalian cells using CpG island and promoter arrays in order to find novel genes that are methylated during differentiation. Also our results on tissue specific methylation during mouse development indicate that some genomic regions with tissue-specific methylation and expression are conserved between mouse and human and suggest that DNA methylation may have an important role in regulating differentiation and tissue-/cell-specific gene expression of some genes.
Lab of Dr. Dominic Smiraglia (Jan 2004-Sept 2005):
Methylation of CpG islands within promoter regions of genes has been associated with gene silencing, suggesting loss of tumor suppressor function and tumorigenesis. Promoter hypermethylation is a frequent, non-random event in cancers of most organs including the cervix, breast, prostate etc. Hypermethylation may occur in cancer precursors and that the number of methylation events increases with progression, paralleling the accumulation of genetic changes. Using RLGS, we focused on genome wide scanning for frequently methylated genes, including genes not previously implicated in carcinogenesis that may be used to develop promising panels of biomarkers for cancer screening and other applications. We compiled an extensive list of possible methylation targets in cervical neoplasia, breast cancer and prostate cancer using RLGS. From our panel of most frequently methylated genes in cervical cancer that we identified by RLGS, we developed quantitative Methylation Specific PCR (MethLight) assays for two novel DNA methylation biomarkers that are specific for cervical cancer and have validated the results. We have identified a list of novel genes that are epigenetically altered in human breast and prostate cancers. Work is in progress to validate these results in larger sample sets. Our RLGS studies have also identified a few novel genes that are methylated in tissue specific as well as germ layer specific manner in normal human adults. We have confirmed these results by Methylation specific massArray.
Post-Doctoral Fellow: State University of New York at Buffalo, Buffalo, NY, USA - 2003-2004
Topic of research: Drosophila model of Huntington’s disease (HD)
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by expansion of polyglutamine [Poly (Q)] repeats beyond the threshold value of 38, in the amino terminal portion of a predominately cytosolic protein, huntingtin (htt). This results in the appearance of intranuclear inclusions in affected neurons and cytosolic aggregates in the neuronal processes (neuropil) of HD patient brains. Our laboratory identified the protein product Drosophila myeloid leukemia factor (dMLF) because of its similarity to human protein MLF and also an orthlog of a brain enriched chaperone, the human MRJ (mammalian relative of DnaJ), both of which colocalize with the aggregates and suppresses Poly (Q) toxicity in a Drosophila model of Poly (Q) diseases. My work was to identify the domains of dMLF required for suppression of Poly (Q) toxicity and also to identify the roles played by modifiers of dMLF on its suppressing effect of polyglutamine toxicity and colocalization with the aggregates.We also showed that in the photoreceptors, expression of another suppressor with a J domain, dHDJ1, but not dMRJ, prior to expression of expanded Poly (Q)s dramatically promoted cytoplasmic aggregation. Biochemical analyses of both proteins showed increased level of detergent-soluble, monomeric Poly (Q)-expanded proteins. These findings exemplified the functional similarities and differences between J domain proteins in suppressing Poly (Q) toxicity.
Post-Doctoral Fellow: Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA - 2000-2003
Topic of research: Drosophila models of Polyglutamine diseases and Amyotrophic lateral sclerosis (ALS)
Most human neurodegenerative diseases have a number of features in common including adult onset, progressive degeneration of selected neuronal populations, and the formation of abnormal protein aggregates. Although these shared characteristics raise the possibility of conserved pathogenic mechanisms, the diverse clinical and pathologic features of each disorder indicate significant differences as well. By directly comparing modifiers isolated in models of polyglutamine diseases and from a Drosophila model of tauopathy we find a final common pathway of cell death involving apoptosis. Among the polyglutamine diseases, protein folding and histone acetylation are key common mediators. In addition, two novel modifiers suggest shared pathways of toxicity among all the disorders. Since cell type specificity is a highly salient feature of all neurodegenerative diseases, but most work to date in Drosophila models has been performed in the retina, we determined if similar pathways of toxicity operate in neurons of the Drosophila brain. Many, but not all, retinal modifiers also modify toxicity in postmitotic neurons in the brain. Analysis of polyglutamine toxicity in the adult brain facilitated identification of nicotinamide (Vitamin B3), a vitamin with histone deacetylase inhibiting activity, as a potent suppressor of polyglutamine toxicity. These findings outline common pathways of neurotoxicity, demonstrate of disease- and cell-type specific pathways, and identify a common vitamin as a potential therapy in polyglutamine disorders.
Amyotrophic lateral sclerosis (ALS) is one of the most common adult onset neurodegenerative diseases and is characterized by selective loss of motor neurons, ultimately leading to progressive atrophy of skeletal muscles. The discovery of missense mutations in genes coding for Cu/Zn superoxide dismutase 1 (SOD1) in familial cases has led to the development of mouse models that portray the motor neuron degeneration syndrome of the human disease. We have generated several transgenic flies using different Cu/Zn hSOD1 mutations. Work is in progress to establish them as a faithful model of the toxic human disease and effectively use them for genetic dissection of the fundamental pathogenetic mechanisms underlying the disease.
Summary of Ph.D Work:
Topic of research: Chromatin compaction in Drosophila polytene chromosomes
Chromatin despiralization has been shown to be independent of its transcriptional properties and is controlled by some cis- and trans- acting factors in Drosophila melanogaster. My study, undertaken with the intention to identify genomic regions (‘modifiers’) that can alter the haplo X- chromatin compaction of the mutant, giant (gt: 1-0.9), without affecting its transcriptive activity, has exposed trans-acting loci viz. gt, II chromosome giant (gt4), Suppressor of Hairless [Su (H)S5], Suppressor of zeste [Su (z)], Suppressor of variegation [T(Y;3) Su (var)] Enhancer of zeste [E (z)] and Enhancer of variegation [E(var)55]. The wild type products of these genes play an active role in changing the chromosomal morphology of the polytene male Xs of the gt mutant. While the gt4 and Su (var) mutants made the gt haplo X chromosome very much swollen, diffuse and puffy (SDP), the Su (H)S5 , Su(z), E(z) and E(var)55 rendered the gt male X- chromosome hypercompacted. But all these cases of altered chromosomal morphology of the gt haplo X, did not affect its transcriptive activity, as confirmed by the autoradiographic studies. Interestingly, treatment of the SDP classes viz. gt; gt4 interacting class and also the In (1) BM (rv) PEV class, with sodium butyrate, reverted back the normal chromosomal morphology of the haplo X- chromosomes in these males. RFLP analysis of sodium butyrate treated gt; gt 4male DNAs using methylation sensitive enzymes, confirmed role of sodium butyrate as acetylating agent in bringing about such alteration in the chromosomal morphology. The SDS-PAGE analysis of salivary gland proteins revealed a 50-KDa band in one of the interacting classes viz. gt; gt4 males, which migrated with a similar band of the In (1)BM2 (rv) males , both of which show SDP phenotype. Further probing with 2D-PAGE, indicated the involvement of some novel proteins that were induced in all the genotypes involved in these combination classes. This work led us to propose that the X chromosome is unique both with respect to ‘form’ and ‘function’ and as situations demand it can modulate itself. The gt male X chromosome somehow seems to be ‘permissive’ for allowing access to the products of the mutants mentioned in this work.
2024, North-Eastern Hill University
Designed & developed at Bioinformatics Centre, NEHU
