Manoj Hariharan

Genomic Analysis Laboratory

Manoj Hariharan
Salk Institute for Biological Studies - Manoj Hariharan

Manoj Hariharan


Staff Scientist
Genomic Analysis Laboratory and Center of Excellence for Stem Cell Genomics

Gene expression is an intricately coordinated event. The spatio-temporal regulation of gene expression is controlled at several levels. I focus on three facets - the epigenetic, transcriptional and post-transcriptional layers of gene regulation. As a computational biologist, I analyze genomics data generated by high-throughput technologies in an effort to uncover these molecular connections, with special focus on human health and disease.

The selective chemical modification (addition of a methyl group) at the fifth carbon atom of cytosine in the DNA (commonly referred to as DNA methylation) is a key epigenetic aspect that has direct effects on gene regulation. At the Ecker lab I work towards unraveling the mechanics of how DNA methylation affects gene regulation in a variety of systems. We are part of the ENCODE Consortium Project (phase 3) where we look into the differential methylation patterns across various organs (spatial) in selected stages (temporal) of mouse embryonic development and study its effect on gene expression. These stages correspond to those at which several human developmental disorders are manifested. We have recently discovered several novel patterns of DNA methylation that assert their effects on gene expression profiles of various organs across four individuals.

I play a lead role in the activities of the recently established Center of Excellence for Stem Cell Genomics (CESCG). This center, funded by the California Institute of Regenerative Medicine (CIRM), aims to foster collaborations with stem-cell biologists in the state of California and the two nodal CESCGs (at Salk Institute and Stanford University). We have initiated several interesting projects, which "apply genomics and bioinformatics approaches to stem cell research to accelerate fundamental understanding of human biology and disease mechanisms, enhance cell and tissue production and advance personalized cellular therapeutics." We are collaborating with four of the seven applicants selected for this program: (1) Prof. Gay Crooks at UCLA to identify and overcome transcriptome barriers to generating hematopoietic stem cells from pluripotent stem cells, (2) Prof. Guoping Fan at UCLA for genomic analysis of stem cell differentiation in human overgrowth syndrome, (3) Prof. Kelly Frazer at UCSD for population wide study of functional genomics of drug induced electrophysical phenotypes in human cardiomyocites and (4) Prof. Benoit Bruneau at UCSF to study the epigenomics of human cardiac differentiation and congenital heart disease.

For more information on my research activities (including past research) and background, please visit my website by clicking here»


Education

Postdoctoral associate, Stanford University, CA
Postdoctoral fellow, Yale University, CT
PhD in Biotechnology, University of Pune, Pune, India (Bioinformatics work done at the CSIR Institute for Genomics and Integrative Biology, Delhi)
MSc in Bioinformatics, Bharathiar University, Coimbatore, India.
BSc in Biotechnology, Dr. GRD College of Science, Coimbatore, India.

Awards & Honors

  • Patent granted: Human microRNA targets in HIV (PCT/IB2006/002802 & US/7825230)
  • Patent filed: Targets for human microRNAs in Avian Influenza virus genome (US/200845472)
  • Senior Research Fellowship from Council for Scientific & Industrial Research Ministry of Science & Technology India (Apr 2007 - Feb 2009)
  • Selected as AAAS (American Association for the Advancement of Science) member through Program for Excellence in Science; member since May 2012.
  • Short-listed for the Merck Millipore India Innovation Award 2012.

Selected Publications

  • For full list please click here»
  • Schultz M.D., He Y, Whitaker J, Hariharan M, Mukamel E.A., Leung D, Rajagopal N, Nery J, Urich M, Chen H, Lin S, Lin Y, Jung I, Schmitt A, Selvaraj S, Ren B, Sejnowski T, Wang W, Ecker JR. (2015) Human Body Epigenome Maps Reveal Noncanonical DNA Methylation Variation. Nature; in press.
  • Leung D, Jung I, Rajagopal N, Schmitt A, Selvaraj S, Lee AY, Yen CA, Lin S, Lin Y, Qiu Y, Xie W, Yue F, Hariharan M, Ray P, Kuan S, Edsall L, Yang H, Chi NC, Zhang MQ, Ecker JR, Ren B. (2015) Integrative analysis of haplotype-resolved epigenomes across human tissues. Nature; 518(7539):350-4
  • Roadmap Epigenomics Consortium. (2015) Integrative analysis of 111 reference human epigenomes. Nature; 518(7539):317-30.
  • Ma H, Morey R, O'Neil RC, He Y, Daughtry B, Schultz MD, Hariharan M, Nery JR, Castanon R, Sabatini K, Thiagarajan RD, Tachibana M, Kang E, Tippner-Hedges R, Ahmed R, Gutierrez NM, Van Dyken C, Polat A, Sugawara A, Sparman M, Gokhale S, Amato P, Wolf DP, Ecker JR, Laurent LC, Mitalipov S. (2014) Nature; 511(7508):177-83.
  • Laddha SV, Nayak S, Paul D, Reddy R, Sharma C, Jha P, Hariharan M, Agrawal A, Chowdhury S, Sarkar C, Mukhopadhyay A. Genome-wide analysis reveals downregulation of miR-379/miR-656 cluster in human cancers. (2013) Biol Direct; 8:10.
  • Soon WW, Hariharan M, Snyder MP. (2013) High-throughput sequencing for biology and medicine. Mol Syst Biol. ;9:640.
  • Gerstein, M.B., Kundaje, A., Hariharan, M., Landt, S.G., Yan, K., Cheng, C., Mu, X., Khurana, E., Rozowsky, J., Alves, P., Abyzov, A., Addleman, N., Alexander, R., Bhardwaj, N., Boyle, A.B., Cayting, P., Charos, A., Cheng, Y., Clarke, D., Eastman, C., Euskirchen, G., Frietze, S., Gertz, J., Grubert, F., Harmanci, A., Jain, P., Kasowski, M., Lacroute, P., Leng J., Lian, J., Min, R., Monahan, H., O'Geen, H., Ouyang, Z., Partridge, E.C, Patacsil, D., Pauli, F., Raha, D., Ramirez, L., Reddy, T.E., Reed, B., Shi, M., Slifer, T., Wang, C., Wu, L., Yang, X., Yip, K., Zilberman-Schapira, G., Batzoglou, S., Sidow, A., Farnham, P.J., Myers, R., Weissman, S.M. and Snyder, M. (2012) Architecture of the human regulatory network derived from ENCODE data. Nature 489(7414):91-100.
  • The ENCODE Project Consortium. (2012) An Integrated Encyclopedia of DNA Elements in the Human Genome. Nature 489(7414):57-74.
  • Boyle, A.P., Hong, E.L., Hariharan, M., Cheng, Y., Schaub, M.A., Karczewski, K.J., Park, J., Hitz, B.C., Weng, S., Cherry, J.M. and Snyder, M. (2012) Annotation of Functional Variation in Personal Genomes Using RegulomeDB. Genome Res. 22(9):1790-7.
  • Chen, R., Mias, G.I., Li-Pook-Than, J., Lam, H., Jiang, L., Chen, R, Miriami, E., Karczewski, K., Hariharan, M., Dewey, F.E., Lin, S., Habegger, H., Clark, M.J., Balasubramanian, S., Cheng, Y., O'Huallachain, M., Dudley, J., Hillemenyer, S., Haraksingh, R., Sharon, D., Euskirchen, G., Lacroute, P., Bettinger, K., Im, H., Boyle, A.P., Kasowski, M., Grubert, F., Seki, S., Garcia, M., Whirl-Carrillo, M., Gallardo, M., Blasco, M.A., Greenberg.P.L., Snyder, P., Klein, T.E., Altman, R.B., Butte, A., Ashley, E.A., Nadeau, K., Gerstein, M., Tang, H. and Snyder, M. (2012) Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes. Cell 148, 1293-1307.
  • 11. Wu, J., Seay, M., Schulz, V., Hariharan, M., Tuck, D., Lian J., Du, J., Shi, M., Ye, Z., Gerstein, M., Snyder, M., Weissman, S. (2012) TCF7 Is an Important Regulator of the Switch of Self-Renewal and Differentiation in a Multipotential Hemopoietic Cell Line. PLoS Genetics 8(3): e1002565.
  • Gokhale, S., Hariharan, M., Brahmachari, S.K. and Gadgil, C. (2012) A simple method for incorporating dynamic effects of intronic miRNA mediated regulation. Mol Biosyst. 8(8):2145-52.
  • Kasowski M., Grubert F., Heffelfinger C., Hariharan M., Asabere A., Waszak, S.M., Habegger L., Rozowsky J., Shi M., Urban A., Hong M.Y., Weissman S.M., Gerstein M., Korbel, J. and Snyder M (2010) Variation in Transcription Factor Binding Among Humans. Science 328(5975):232-5.
  • Bargaje, R., Hariharan, M., Scaria, V., Pillai, B. (2010) Consensus miRNA expression profiles derived from interplatform normalization of microarray data. RNA 16(1): 16-25.
  • Ahluwalia, J.K., Hariharan, M., Bargaje, R., Pillai, B., and Brahmachari, V. (2009) Incomplete penetrance and variable Expressivity: Is there a microRNA connection? Bioessays 31(9):981-982
  • Hariharan, M., Scaria, V., and Brahmachari, S.K. (2008) dbSMR: A Novel Resource of Genome-wide SNPs affecting MicroRNA Mediated Regulation. BMC Bioinformatics;10:108
  • Sharma, A., Kumar, M., Aich, J., Hariharan, M., and Brahmachari, S.K., Agrawal, A. and Ghosh, B. (2008) Post transcriptional regulation of Interleukin-10 expression by hsa-miR-106a. Proc Natl Acad Sci U S A. 106(14):5761-6.
  • Ahluwalia, J.K., Khan, S.Z., Soni, K., Gupta, A., Hariharan, M., Scaria, V., Patowary, A., Lalwani, M., Sivasubbu, S., Pillai, B., Mitra, D. and Brahmachari, S.K. (2008) Human cellular microRNA hsa-miR-29a interferes with viral nef protein expression and HIV-1 replication. Retrovirology; 23;5:117
  • Arora, A., Dutkiewicz, M., Scaria, V., Hariharan, M., Maiti, S and Kurreck, J. (2008) Inhibition of translation in living eukaryotic cells by an RNA G-quadruplex motif. RNA. 7:1290-6.
  • Indian Genome Variation Consortium. (2008) Genetic landscape of the people of India: a canvas for disease gene exploration. J Genet. 87(1):3-20.
  • Hariharan, M., Scaria, V., Pillai, B., and Brahmachari, S.K. (2005) Targets for human encoded microRNAs in HIV genes. Biochem.Biophys.Res.Commun. 337: 1214-1218.