Dr. Prabha Sampath obtained her Ph.D. in Molecular Medicine in Cleveland Clinic Foundation, Ohio, United States in 2004. Working on gene regulation during inflammation, Dr. Sampath elucidated RNA and protein factors comprising major pathways in inflammation. As a postdoctoral fellow at the Center for Cardiovascular and Regenerative Medicine, University of Washington, Dr. Sampath worked on translational control mechanisms in embryonic stem cell differentiation. Dr. Sampath is the recipient of prestigious A*STAR Investigatorship award and she joined the Institute of Medical Biology, Biopolis, Singapore to set up her own research group in May 2008. She is now a Senior Principal Investigator at IMB, holds an adjunct position at Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore and Duke-NUS School of Medicine.
I have a long-standing research interest in translational control and its involvement in human pathology. My objective is to understand the molecular mechanisms underlying dysregulated translational regulation in pathophysiology, and build upon these findings to develop targeted therapeutic strategies. Our focus has led to exciting discoveries in disease conditions such as chronic wounds, aggressive cancers, and neuronal disorders. Glioblastoma multiforme, a devastating brain cancer associated with very poor clinical outcomes, frequently relapses after therapy due to the persistence of intrinsically resistant cancer stem cells. We have identified a microRNA - miR-138 - which is critical to the survival and proliferation of these glioma stem cells. We envision that our therapeutic strategy targeting this microRNA, would prevent relapse of these deadly tumours. We have also discovered another microRNA, miR-198, which lies at the heart of a molecular pathway governing both cancer progression and wound healing in epithelia. We are following up on this discovery with the aim of finding new strategies to tackle both chronic wounds and epithelial cancers. Translational control of gene expression defines the proteome and differentially translated genes in a specific pathological condition mirror the spectrum of proteins synthesized. Visualizing these interactions at the molecular level, and integrating this information in the framework of pathophysiology my objective is to identify specific therapeutic targets and equally specific innovative therapeutics.
Mazumder B, Sampath P, Seshadri V, DiCorleto PE and Fox PL. Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control. Cell. 2003 Oct 17;115(2):187-98.
Sampath P, Mazumder B, Seshadri V, Gerber CA, Dignam JD, Driscoll DM, and Fox PL.Noncanonical function of glutamyl-prolyl-tRNA synthetase: gene-specific silencing of translation. Cell. 2004 Oct 15;119(2):195-208.
Sampath P, Pritchard DK, Reinecke H, Schwartz SM, Morris DR, and Murry CE. A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation. Cell Stem Cell. 2008 May 8;2(5):448-60. doi: 10.1016/j.
Chan XH, Nama S, Rizk P, Ow GS, Ivshina AV, Tanavde V, Haybaeck J, Kuznetsov V and Sampath P. Targeting glioma stem cells by functional inhibition of a prosurvival oncomiR-138 in malignant gliomas. Cell Rep. 2012 Sep 27;2(3):591-602. doi: 10.1016/j.celrep.2012.07.012. Epub 2012 Aug 24.
Sundaram GM, Common JE, Srikanta S, Lim TC, Lane EB and Sampath P. 'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature. 2013 Mar 7;495(7439):103-6. doi: 10.1038/nature11890.
Sundaram, G., and Sampath, P., Regulation of Context-specific Gene Expression by Posttranscriptional Switches Transcription 2013 Sep 13;4(5).
Sundaram GM, Ismail HM, Muhuri M, Vaz C, Ow GS, Burke B, Kuznetsov V, Lane EB and Sampath P. EGF hijacks miR-198/FSTL1 wound-healing switch and steers a two-pronged pathway toward metastasis. J Experimental Medicine. 2017 Oct 2;214(10):2889-2900. doi: 10.1084/jem.20170354.
Tan DSW, Chong FT, Toh SY, Lau DP, Kwang XL, Zhang X, Tan GS, Chang MM, Lim WT, Ang MK, Lim TKH and Sampath P, Chowbay B, Skanderup AJ, DasGupta R and Iyer NG. Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma. Nature Medicine. 2017 Oct;23(10):1167-1175. doi: 10.1038/nm.4401.
Yan T, Ooi WF, Ma D, Xing M, Loh YP, Ho JHJ, Ng JJQ, Rozen SG, Ghosh S, Bard FA, Sampath P, Tergaonkar V, Davies JOJ, Hughes JR, Fullwood MJ, Tan P and Li S. HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis. Nature Commun. 2018 Jan 8;9(1):100. doi: 10.1038/41467-017-02601-1.
Di Pascale F, Nama S, Muhuri M, Quah S, Chan XHD, Ramalingam R, Burke B and Sampath P. C/EBPβ mediates RNA polymerase III-driven transcription of oncomiR-138 in malignant gliomas. Nucleic Acids Res. 2018 Jan 9;46(1):336-349. doi: 10.1093/nar/gkx1105.