We study transcriptional and post-transcriptional mechanisms of reprogramming of gene expression and its regulations during disease and development at systems level by integrating computational and experimental tools at systems level. The discovery of microRNAs (miRNAs) as novel regulators of gene expression has led to the formation of a growing new field in biology with important implications for normal development and disease. miRNAs comprise a group of endogenous, small non-coding RNAs that function by binding to their respective target mRNAs, causing them to undergo post- transcriptional repression. miRNAs regulate a significant proportion of all mRNA transcripts within the cell. Aberrant miRNA expression may be regarded as a common feature of many human disorders. New technologies are currently being developed to modulate miRNA expression in vivo, as this may represent a novel therapeutic approach for many diseases. Research program of our group is focused on investigating the role of miRNAs and other non-coding small-RNAs (smRNAs) in disease progression at systems level using the technologies of Next-Gen deep sequencing, microarrays and computational biology/bioinformatics in primarily two human diseases (1) breast cancer (2) polycystic kidney diseases.
1. Reprogramming of gene expression in Breast cancer and its regulation: Using RNA-sequencing we are aiming to discover genetic alterations in breast cancer cells in response to endocrine therapy.
2. Polycystic kidney disease (PKD): PKD is an important genetic disorder leading to renal failure. We are focusing on understanding core set of genes and pathways contributing to initiation and progression of PKD. Our findings suggest an extensive role of miRNAs and other small-RNAs.
3. Tool development: A sub-text of our research program is to develop new computational tools, analysis pipelines, software and databases that may help us integrate and interpret data sets at systems levels.
Using whole transcriptome analysis/(next generation sequencing) to unravel the effect of pre-operative progesterone in operable breast cancer
Collaborators- Tata Memorial Centre, Mumbai
Dweep H, Sticht C, Kharkar A, Pandey P, Gretz N. Parallel analysis of mRNA and microRNA microarray profiles to explore functional regulatory patterns in polycystic kidney disease: using PKD/Mhm rat model. PLoS One. 2013;8(1):e53780.
Ho J, Pandey P, Schatton T, Khalid M, Frank M, Hartwig S and Kreidberg JA. The pro-apoptotic protein Bim is a microRNA target affecting the maintenance of kidney progenitor cells. J Am Soc Nephrol. 2011 Jun;22(6):1053-63.
Pandey P, Qin S, Ho J, and Kreidberg JA. Systems biology approach to identify transcriptional reprogramming and microRNA targets during embryonic Polycystic Kidney Disease progression. BMC Syst Biol. 2011 Apr 25;5:56.
Hartwig S, Ho J*, Pandey P*, MacIsaac K, Taglienti M, Xiang M, Alterowitz G, Marco Ramoni, Fraenkel E and Kreidberg JA. Genomic Characterization of Wilms’ Tumor Suppressor-1 Targets in Nephron Progenitor Cells during Kidney Development. Development. 2010 Apr;137(7):1189-203.
*These authors contributed equally to this work
Shahi P, Loukianiouk S, Bohne-Lang A, Kenzelmann M, Küffer S, Maertens S, Eils R, Gröne HJ, Gretz N, Brors B. Argonaute – a database for gene regulation by mammalian microRNAs. Nucleic Acids Res. 2006 Jan 1;34(Database issue):D115-8. (Featured in top five downloads).