Shyam PRABHAKAR, Ph.D.Group Leader, Computational and Systems Biology
Associate Director, Integrative Genomics
Transcriptional Regulation in Development, Evolution and Disease
Transcriptional changes lie at the heart of 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.
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 – these are analyzed using comparative genomics, next-generation sequencing (NGS) and in vivo enhancer assays. We are also interested in the more recent regulatory changes that make us different from one another. These are identified by performing histone ChIP-seq on multiple individuals within the target population group. On the disease front, we investigate the transcriptional regulatory mechanisms of autism, lung and colon cancer, and specific immune-related diseases. In this space, we use single-cell RNA-seq and histone ChIP-seq on a large scale.
On the experimental side, we continuously develop and refine NGS-based techniques for whole-genome chromatin profiling and enhancer identification. In parallel, we have created novel computational tools for analyzing NGS data, that draw upon ideas from optimal signal processing, equilibrium thermodynamics and structural biology. We are also developing new statistical methods for associating polymorphisms with chromatin state variation using NGS data. Finally, we have constructed a custom bioinformatic pipeline for single-cell transcriptomic data, with applications in early embryonic development and cancer genomics.
|2000||PhD, Applied Physics, Stanford University|
|1992||BTech, Electronics & Communications Engineering, Indian Institute of Technology, Madras|
|2012-||Associate Director, Integrative Genomics, Genome Institute of Singapore|
|2011-||Group Leader, Genome Institute of Singapore|
|2007-11||Senior Research Scientist, Genome Institute of Singapore|
|2003-07||Postdoctoral Fellow, EM Rubin lab, Genomics Division, Lawrence Berkeley National Laboratory|
|2000-03||Postdoctoral 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
|2013||Grant review panel: bilateral grant call issued by BMBF (Germany) and ANR (France)|
|2014||Grant review Panel: A*STAR Young Investigator Grants|
|2014||Organizing committee: 9th Asian Epigenomics Meeting|
|10/2009 - 10/2012|
(PI) JCOAG03_FG02_2009: Toward a systems biology framework for estrogen signaling integrating technology, biology and computation by Agency for Science, Technology and Research, Joint Council Office, Singapore (SGD 741,000 over 3 years)
|09/2013 - 09/2016||(PI) JCO1331CFG080: Single Cell Transcriptomic Characterization of Tumour Heterogeneity and Network Analysis of Response to Targeted Therapeutics by Agency for Science, Technology and Research, Joint Council Office, Singapore (SGD 991,000 over 3 years)|
|08/2011 - 06/2015|
(co-PI) 1R01MH094714: Epigenetic and Transcriptional Dysregulation in Autism Spectrum Disorder by National Institute of Mental Health, USA (USD 600,000 -direct costs to my group over 4 years)
- 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 Jan 8. [Epub ahead of print] Abstract
- 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
- TherMos: Estimating protein-DNA binding energies from in vivo binding profiles.
Sun W, Hu X, Lim MH, Ng CK, Choo SH, Castro DS, Drechsel D, Guillemot F, Kolatkar PR, Jauch R, Prabhakar S.
Nucleic Acids Res 2013 Jun 1; 41(11):5555-68 Abstract
- 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
- 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
- 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
- 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
- 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
- Accelerated evolution of conserved noncoding sequences in humans.
Prabhakar S*, Noonan JP*, Pääbo S, Rubin EM (* = equal contribution).
Science. 2006 Nov;314:786. Abstract
- Close sequence comparisons are sufficient to identify human cis-regulatory elements.
Prabhakar S, Poulin F, Shoukry M, Afzal V, Rubin EM, Couronne O, Pennacchio LA.
Genome Research. 2006 Jul;16:855-63. Abstract
Complete Publications List