Senior Investigator

Shyam PRABHAKAR, Ph.D.
Group Leader, Computational and Systems Biology
Associate Director, Integrative Genomics
 
Research Focus

Transcriptional Regulation in Development, Evolution and Disease

Organismal development is driven by spatiotemporal changes in gene expression that generate hundreds of cell types from a single totipotent cell. These changes can be rewound by over-expressing a handful of embryonic genes in adult cells. Similarly, morphological differences between species are also thought to be driven largely by transcriptional regulatory changes. Finally, the majority of genetic mutations responsible for common diseases reside within gene-regulatory sequences such as enhancers, promoters and insulators. Thus, transcriptional regulation lies at the heart of development, evolution and disease.

We use a combination of wet-lab and dry-lab approaches to study human transcriptional regulation. Regulatory sequences that drove human and primate evolution are a major focus – we study them using comparative genomics, next-generation sequencing (NGS) and in vivo enhancer assays. We are also interested in the more recent regulatory changes that generate diversity in human populations. These are identified using a combination of cohort-scale histone ChIP-seq and novel statistical techniques for regulatory QTL analysis. On the disease front, we investigate the transcriptional regulatory mechanisms of autism, lung and colon cancer, and specific immune-related diseases. In addition to chromatin profiling, we tackle the above scientific questions through single-cell RNA sequencing.



Education

2000 PhD, Applied Physics, Stanford University
1992 BTech, Electronics & Communications Engineering, Indian Institute of Technology, Madras


Professional Appointments

2012-Associate Director, Integrative Genomics, Genome Institute of Singapore
2011-Group Leader, Genome Institute of Singapore
2007-11Senior Research Scientist, Genome Institute of Singapore
2003-07Postdoctoral Fellow, EM Rubin lab, Genomics Division, Lawrence Berkeley National Laboratory
2000-03Postdoctoral Fellow, Samuel Karlin group, Dept. of Mathematics, Stanford University


Honors and Awards


2008 First prize: poster competition at HUGO 13th Human Genome Meeting
2001 American Physical Society Award for Outstanding Doctoral Thesis Research in Beam Physics


Committee and Advisory Board

2013Grant review panel: bilateral grant call issued by BMBF (Germany) and ANR (France)
2014Grant review Panel: A*STAR Young Investigator Grants
2014Organizing committee: 9th Asian Epigenomics Meeting


External Grant

2015-Jan01 - 2018-Dec31(PI) NRF2013-THE001-093 SynBioLogics: A Platform for Rational Design of Human Cells for Synthesis of Biologics by NRF, Singapore (SGD 4,345,000)
2013-Sep13 - 2016-Sep12(PI) JCO1331CFG080: Single Cell Transcriptomic Characterization of Tumour Heterogeneity and Network Analysis of Response to Targeted Therapeutics by A*STAR JCO, Singapore (SGD 991,000)
2013-Dec01 - 2015-Nov30(PI) IAF111118: Validation of the Chromatin Immunoprecipitation Assay Kit LysoChIP by SG Microlab Devices and A*STAR, Singapore (SGD 105,000)
2012-Sep26 - 2012-Dec31(PI) IAF311010 JAIC: Multidecades Ethnic Study Pilot Phase by Procter & Gamble and A*STAR, Singapore (SGD 50,000)
2012-Dec19 - 2014-Jun30(PI) IAF111085: Optimizing Data Storage Infrastructure for Genomic Applications by Hitachi and A*STAR, Singapore (SGD 350,000)
2011-Aug25 - 2015-Jun30(co-PI) 1R01MH094714: Epigenetic and Transcriptional Dysregulation in Autism Spectrum Disorder by NIMH, USA (USD 600,000)
2009-Oct15 - 2012-Oct14(PI) JCOAG03_FG02_2009: Toward a systems biology framework for estrogen signaling integrating technology, biology and computation by A*STAR JCO, Singapore (SGD 741,000)


Selected Publications

  1. Noncoding Origins of Anthropoid Traits and a New Null Model of Transposon Functionalization.
    del Rosario RC, Rayan NA, Prabhakar S.
    Genome Research 2014 Sep; 24(9):1469-84. Abstract     

  2. Dynamic developmental signaling logic underlying lineage bifurcations during human endoderm induction and patterning from pluripotent stem cells.
    Loh KM, Ang LT, Zhang J, Kumar V, Ang J, Auyeong JQ, Lee KL, Nichane M, Poellinger L, Chen Q, Prabhakar S, Weissman IL, Lim B.
    Cell Stem Cell 2014 Feb 6; 14(2):237-52. Abstract     

  3. Uniform, optimal signal processing of mapped deep-sequencing data.
    Kumar V, Muratani M, Rayan NA, Kraus P, Lufkin T, Ng HH, Prabhakar S.
    Nat Biotechnol 2013 July; 31(7):615-22. Abstract     

  4. TherMos: Estimating protein-DNA binding energies from in vivo binding profiles.
    Sun W, Hu X, Lim MH, Ng CK, Choo S, Castro D, Drechsel D, Guillemot F, Kolatkar PR, Jauch R, Prabhakar S.
    Nucleic Acids Res 2013 Jun 1; 41(11):5555-68. Abstract     

  5. Comprehensive prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimers.
    Jankowski A, Szczurek E, Jauch R, Tiuryn J, Prabhakar S.
    Genome Res 2013 Aug;23(8):1307-18. Abstract     

  6. In Vivo epigenomic profiling of germ cells reveals germ cell molecular signatures.
    Ng JH, Kumar V, Muratani M, Kraus P, Yeo JC, Yaw LP, Xue K, Lufkin T, Prabhakar S#, Ng HH#. (#: corresponding author)
    Dev Cell 2013 Feb 11; 24(3):324-33. Abstract     

  7. Ncoa3 functions as an essential Esrrb coactivator to sustain embryonic stem cell self-renewal and reprogramming.
    Percharde M, Lavial F, Ng JH, Kumar V, Tomaz RA, Martin N, Yeo JC, Gil J, Prabhakar S, Ng HH, Parker MG, Azuara V.
    Genes Dev 2012 Oct 15; 26(20):2286-98. Abstract     

  8. Integrative model of genomic factors for determining binding site selection by estrogen receptor-alpha.
    Joseph R, Orlov YL, Huss M, Sun W, Kong SL, Ukil L, Pan YF, Li G, Lim M, Thomsen JS, Ruan Y, Clarke ND, Prabhakar S, Cheung E, Liu ET.
    Mol Syst Biol 2010 Dec 21;6:456. Abstract     

  9. Human-specific gain of function in a developmental enhancer.
    Prabhakar S, Visel A, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Morrison H, FitzPatrick DR, Afzal V, Rubin EM, Noonan JP.
    Science. 2008 Sep;321:1346-50. Abstract     

  10. Accelerated evolution of conserved noncoding sequences in humans.
    Prabhakar S*, Noonan JP*, Pääbo S, Rubin EM (* = equal contribution).
    Science. 2006 Nov;314:786. Abstract     



Complete Publications List



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