Shyam PRABHAKAR, Ph.D.
Group Leader,
Associate Director, Integrated Genomics
prabhakars@gis.a-star.edu.sg

 

RESEARCH FOCUS
 

Transcriptional Regulation, Epigenomics, Computational Genomics, Evolutionary Genomics

We owe our position as "higher organisms" on the evolutionary ladder to the complexity and abundance of functional non-protein-coding sequences in our genome. These include tens of thousands of transcriptional regulatory elements that turn neighbouring genes on or off at the right time and place, control every aspect of human development, and contribute to disease when they go awry.

My lab is focused on transcriptional regulatory elements in the human genome: their sequence signatures, epigenetic patterns, molecular function, evolutionary dynamics, network interactions, systems biology, and role in human development and disease. We use wet-lab and dry-lab approaches in equal measure.

Key areas of interest include epigenomic mapping, TF-DNA binding, functional and disease-causing noncoding variants, algorithm development for next-gen sequence data, stem cell differentiation, embryonic development and human evolution.

These topics are addressed by integrating comparative genomics, in vivo and in vitro regulatory assays, high-throughput sequencing, whole-genome functional data sets, biochemical modeling, and concepts and techniques from statistics, information theory, machine learning and molecular evolution.

 

EDUCATION

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

 

PROFESSIONAL APPOINTMENTS

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

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

 

EXTERNAL GRANT
 

10/2009 - 10/2012 (PI,PD) 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)
08/2011 - 06/2015 (co-PI) 1R01MH094714: Epigenetic and Transcriptional Dysregulation in Autism Spectrum Disorder by National Institute of Mental Health, USA (USD 2,123,000 - direct costs over 4 years)

 

COMPLETE PUBLICATION LIST

1.   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, accepted.
 
2.   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 Apr 16.
 
3.   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 Apr 3.
 
4.   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.
 
5.   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 Epub 2012 Sep 26.
 
6.   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
 
7.   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.
 
8.   Ultraconservation identifies a small subset of extremely constrained developmental enhancers.
Visel A, Prabhakar S, Akiyama JA, Shoukry M, Lewis KD, Holt A, Plajzer-Frick I, Afzal V, Rubin EM, Pennacchio LA.
Nature Genetics. 2008 Jan;40:158-60.
 
9.   Accelerated evolution of conserved noncoding sequences in humans.
Prabhakar S*, Noonan JP*, Pääbo S, Rubin EM (* = equal contribution).
Science. 2006 Nov;314:786.
 
10.   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.