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Name: Karamjit Singh Dolt
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Nationality: Indian |
Institute:
School of Biological Sciences,
University of Liverpool .
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Qualifications:
Ph.D. (Biochemistry) |
Work being undertaken on behalf of KIDSTEM:
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Investigate the potential of mouse Embryonic Stem Cells (ESCs) and their mesenchymal progeny to undergo nephrogenesis.
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Differential gene expression profiling studies to compare the ESC-derived progenitor cells with metanephric mesenchyme of the mouse embryo.
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Previous Experience:
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As cellular response to hypoxia results into changes in the profile of gene expression and the present study explored the same in murine model, we employed cDNA microarrays to investigate the variations in the transcriptome profile in murine liver in response to ten hours of acute hypobaric hypoxia (AHH), equivalent to ~4,600m (i.e. 426 mmHg). The down-regulation of Sterol regulatory element binding protein (SREBP) target genes appeared distinct as a part of acclimatization response to AHH (Dolt, K. S. et al. Biochem. Biophys. Res.Commun. 2007; 354:148-153.). The changes in gene expression in heart of mice exposed to 10 h of hypobaric hypoxia were also evaluated by cDNA arrays. Our results revealed the effect of AHH on the transcript and protein levels of pro-oxidants and antioxidants. The level of reduced glutathione was found to be significantly decreased which may be the consequence of reduced synthesis along with its increased utilization during the exposure (Karar, J. et al. FEBS Lett. 2007; 581(24):4577-82.
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Cloning, gene characterization and variant specific expression of Hypoxia-inducible factor 1a (HIF-1a) has been performed in high altitude yak. The aim of study was to characterize yak HIF-1α mRNA, find sequence variations compared to other mammals and study variant specific expression of the HIF-1α mRNA in blood, heart, lung, liver and kidney. Additionally, microRNAs (miRNAs), a class of non-coding RNA genes that post-transcriptionally regulate gene expression and play vital role in tissue specification or cell lineage decisions, were exhaustively searched through literature and software tools to help explain how the mRNA was so specifically expressed in the tissues. (Dolt, K. S. et al. Gene 2007; 386:73-80).
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Sequencing the hypoxia responsive genes i.e. Hypoxia-inducible factor 1a (HIF-1a), Erythropoietin (EPO) and 2, 3-Bisphosphoglycerate mutase (2, 3-BPGM) has been carried out to identify the genetic variants (SNPs and multi-allelic markers) in human subjects and the genetic association of these variants to high altitude adaptation was analyzed.
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References:
Karar J, Dolt KS, Mishra MK, Arif E, Javed S, Pasha MA.
Expression and functional activity of pro-oxidants and antioxidants in murine heart exposed to acute hypobaric hypoxia.
FEBS Lett. 2007 Oct 2;581(24):4577-82. Epub 2007 Aug 30.
Dolt KS, Karar J, Mishra MK, Salim J, Kumar R, Grover SK, Qadar Pasha MA.
Transcriptional downregulation of sterol metabolism genes in murine liver exposed to acute hypobaric hypoxia.
Biochem Biophys Res Commun. 2007 Mar 2;354(1):148-53. Epub 2006 Dec 28.
Dolt KS, Mishra MK, Karar J, Baig MA, Ahmed Z, Pasha MA.
cDNA cloning, gene organization and variant specific expression of HIF-1 alpha in high altitude yak (Bos grunniens).
Gene. 2007 Jan 15;386(1-2):73-80. Epub 2006 Aug 23.
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