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Scientist Profile

Harinder Singh

Staff Scientist, Immunology
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"There is a distinct sense of fulfillment that derives from creating a device or a drug with a real-world impact."

Deep down the reason that I was attracted to join Genentech is because it attempts to combine the best elements of an academic culture with those from the translational research and commercial domains. It represents an innovative and focused organization with a vital biomedical mission.

As a second-generation molecular biologist, I maintain a strong interest in the rich history of biotechnology. Therefore, I was also drawn to Genentech because of its central position in spawning the generation of biopharmaceuticals after the advent of recombinant DNA. Being at Genentech not only enables me to continue my creative research endeavors, but also challenges me to seek a deeper understanding of immunological disease processes and direct the development of novel and highly effective therapeutics.

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My Focus

My laboratory is assembling and analyzing gene regulatory networks that orchestrate the development of various cell types of the innate and adaptive immune system including B-and T lymphocytes, macrophages, neutrophils dendritic and mast cells. These networks are comprised of inter-connected transcription factors, signaling molecules and miRNAs that regulate cell fate choice and developmental transitions. We are currently utilizing a combination of genetic, molecular and mathematical modeling approaches to further analyze such gene regulatory networks. These include: ChIPseq to connect each transcription factor in a given network with its large set of target genes and high throughput functional screens of lineage- and stage-specific cis-regulatory elements.

We are also interested in manipulating these regulatory networks to engineer stem cells to efficiently adopt particular immune cell fates. Over the past few years I have been shifting the focus of some of our basic research from analyzing molecular circuits that control the development of innate and adaptive immune cells to those that control their activation and function in the context of an immune response.

The move to Genentech is greatly accelerating this process. In the final analysis we seek not only to advance knowledge and understanding in this field but to effectively harness it to enhance the human condition by ameliorating or inhibiting immune-mediated disease processes.

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Publications & Recognition
  • A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates
  • Immunity 2009; doi:10.1016/j.immuni.2009.07.011
  • Spooner CJ, Cheng JX, Pujadas E, Laslo P, Singh H
  • View Abstract on PubMed
  • Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development
  • Nat Immunol 2009; doi:10.1038/ni.1785
  • Mandal M, Powers SE, Ochiai K, Georgoupoulos K, Kee BL, Singh H, Clark MR
  • View Abstract on PubMed
  • Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
  • Nat Immunol 2008; 9:927-936
  • Reynaud D, Demarco I, Reddy K, Schjerven H, Bertolino E, Chen Z, Smale ST, Winandy S, Singh H
  • View Abstract on PubMed
 
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  • Center for Cancer Research, Massachusetts Institute of Technology
  • Postdoctoral Fellow
  • 1984-1988
  • Northwestern University Molecular Biology and Cell Biology
  • Ph.D
  • 1984
  • Punjab Agricultural University
  • M.Sc./B.Sc.
  • 1979
Publications & Recognition
  • A recurrent network involving the transcription factors PU.1 and Gfi1 orchestrates innate and adaptive immune cell fates
  • Immunity 2009; doi:10.1016/j.immuni.2009.07.011
  • Spooner CJ, Cheng JX, Pujadas E, Laslo P, Singh H
  • View Abstract on PubMed
  • Ras orchestrates exit from the cell cycle and light-chain recombination during early B cell development
  • Nat Immunol 2009; doi:10.1038/ni.1785
  • Mandal M, Powers SE, Ochiai K, Georgoupoulos K, Kee BL, Singh H, Clark MR
  • View Abstract on PubMed
  • Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
  • Nat Immunol 2008; 9:927-936
  • Reynaud D, Demarco I, Reddy K, Schjerven H, Bertolino E, Chen Z, Smale ST, Winandy S, Singh H
  • View Abstract on PubMed
  • Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments
  • Nat Immunol 2008; 9:802-809
  • Schlimgen RJ, Reddy KL, Singh H, Krangel MS
  • View Abstract on PubMed
  • Transcriptional repression mediated by repositioning of genes to the nuclear lamina
  • Nature 2008; 452:243-247
  • Reddy K, Zullo J, Bertolino E, Singh H
  • View Abstract on PubMed
  • The double histone acetyltransferase complex ATAC is essential for mammalian development
  • Mol Cell Biol 2008 Dec 22
  • Guelman S, Kozuka K, Mao Y, Pham V, Solloway MJ, Wang J, Wu J, Lill JR, Zha J
  • View Abstract on PubMed
  • Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling
  • Immunity 2008; 28:335-345
  • Johnson K, Hashimshony T, Sawai CM, Pongubala JM, Skok JA, Aifantis I, Singh H
  • View Abstract on PubMed
  • Transcription factor EBF restricts alternate lineage options and promotes B cell fate commitment independently of Pax5
  • Nat Immunol 2008; 9:205-215
  • Pongubala JM, Northrup DL, Lancki DW, Medina KL, Treiber T, Bertolino E, Thomas M, Grosschedl R, Allman D, Singh H
  • View Abstract on PubMed
  • Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation
  • Immunity 2006; 25:225-236
  • Sciammas R, Shaffer AL, Schatz JH, Zhao H, Staudt LM, Singh H
  • View Abstract on PubMed
  • Multilineage transcriptional priming and determination of alternate hematopoietic cell fates
  • Cell 2006; 126:755-766
  • Laslo P, Spooner CJ, Warmflash A, Lancki D, Lee HJ, Sciammas R, Gantner B, Dinne A, Singh H
  • View Abstract on PubMed
  • Regulation of IL-7 dependent immunoglobulin heavy-chain gene rearrangements by transcription factor Stat5
  • Nature Imm.2005; 6:836-843
  • Bertolino E, Reddy K, Medina KL, Parganas E, Ihle J, Singh, H
  • View Abstract on PubMed
  • Assembling a gene regulatory network for specification of the B cell fate
  • Developmental Cell 2004; 7:607-617
  • Medina KL, Pongubala JM, Reddy KL, Lancki DW, DeKoter R, Kieslinger M, Grosschedl R, Singh H
  • View Abstract on PubMed
  • Early B cell factor cooperates with Runx1 and mediates epigenetic changes associated with mb-1 transcription
  • Nature Imm. 2004; 5:1069-1077
  • Maier H, Ostraat R, Gao H, Fields S, Shinton SA, Medina KL, Ikawa T, Murre C, Singh H, Hardy RR, Hagman J
  • View Abstract on PubMed
  • Regulation of macrophage and neutrophil cell fates by the PU.1 to C/EBPa ratio and G-CSF
  • Nature Imm. 2003; 4:1029-1036
  • Dahl R, Walsh JC, Lancki D, Laslo P, Iye SR, Singh H, Simon MC
  • View Abstract on PubMed
  • IRF-4,8 orchestrate the pre-B-to-B transition in lymphocyte development
  • Genes Dev. 2003; 17:1703-1708
  • Lu R, Medina KL, Lancki DW, Singh H
  • View Abstract on PubMed
  • Crystal structure of PU.1/IRF-4/DNA ternary complex
  • Molecular Cell 2002; 10:1097-1105
  • Escalante CR, Brass AL, Pongubala JMR, Shatova E, Singh H, Aggarwal AK
  • View Abstract on PubMed
  • Cooperative and antagonistic interplay between PU.1 and GATA-2 in the specification of myeloid cell fates
  • Immunity 2002; 17:665-676
  • Walsh JC, DeKoter RP, Lee HJ, Smith ED, Lancki DW, Gurish MF, Friend DS, Stevens RL, Anastasi J, Singh H
  • View Abstract on PubMed
  • POU/TBP cooperativity: a mechanism for enhancer action from a distance
  • Molecular Cell 2002; 10:397-407
  • Bertolino E, Singh H
  • View Abstract on PubMed
  • Interferon regulatory factor 4 (IRF-4) interacts with NFATc2 to modulate IL-4 gene expression
  • J. Exp. Med. 2002; 195:1003-1012
  • Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH
  • View Abstract on PubMed
  • Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development
  • Science 2002; 296:158-162
  • Kosak ST, Skok JA, Medina KL, Riblet R, Le Beau MM, Fisher AG, Singh H
  • View Abstract on PubMed
  • PU.1 regulates expression of the interleukin-7 receptor in lymphoid progenitors
  • Immunity 2002; 16:297-309
  • DeKoter RP, Lee HJ, Singh H
  • View Abstract on PubMed
  • Regulation of B lymphocyte and macrophage development by graded expression of PU.1
  • Science 2000; 288:1439-1441
  • DeKoter RP, Singh H
  • View Abstract on PubMed
  • Regulation of B lymphocyte and macrophage development by graded expression of PU.1
  • Science 2000; 288:1439-1441
  • DeKoter RP, Singh H
  • View Abstract on PubMed
  • Regulation of B lymphocyte and macrophage development by graded expression of PU.1
  • Science 2000; 288:1439-1441
  • DeKoter RP, Singh H
  • View Abstract on PubMed
  • PU.1, a shared transcriptional regulator of lymphoid and myeloid cell fates
  • Cold Spring Harbor Symposia on Quantitative Biology 1999; 64:13-20
  • Singh H, DeKoter RP, Walsh JC
  • View Abstract on PubMed
  • Assembly requirements of PU.1-Pip (IRF-4) activator complexes: inhibiting function in vivo using fused dimers
  • EMBO J. 1999; 18:977-991
  • Brass AL, Zhu AQ, Singh H
  • View Abstract on PubMed
  • PU.1 regulates both cytokine-dependent proliferation and differentiation of granulocyte/macrophage progenitors
  • EMBO J. 1998; 17:4456-4468
  • DeKoter RP, Walsh JC, Singh H
  • View Abstract on PubMed
  • Using altered specificity Oct-1 and Oct-2 mutants to analyze the regulation of immunoglobulin gene transcription
  • EMBO J. 1997; 16:7105-7117
  • Shah PC, Bertolino E, Singh H
  • View Abstract on PubMed
  • PU.1 functions in a cell-autonomous manner to control the differentiation of multipotential lymphoid-myeloid progenitors
  • Immunity 1997; 6:437-447
  • Scott EW, Fisher RC, Olson MC, Kehrli EW, Simon MC, Singh H
  • View Abstract on PubMed
  • Pip, a lymphoid-restricted IRF, contains a regulatory domain that is important for autoinhibition and ternary complex formation with the Ets factor, PU.1
  • Genes Dev. 1996; 10:2335-2347
  • Brass AL, Kehrli E, Eisenbeis CF, Storb U, Singh H
  • View Abstract on PubMed
  • Pip, a novel IRF family member, is a lymphoid-specific, PU.1-dependent transcriptional activator
  • Genes Dev. 1995; 9:1377-1387
  • Eisenbeis CF, Singh H, Storb U
  • View Abstract on PubMed
  • Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages
  • Science 1994; 265:1573-1577
  • Scott EW, Simon MC, Anastasi J, Singh H
  • View Abstract on PubMed
  • The v-abl tyrosine kinase negatively regulates NF-kB/Rel factors and blocks kappa gene transcription in pre B lymphocytes
  • Genes Dev. 1994; 8:678-687
  • Klug CA, Gerety SJ, Shah PC, Yunn-Yi C, Rice NR, Rosenberg N, Singh H
  • View Abstract on PubMed
  • Molecular cloning of a lymphoid-specific cDNA encoding a protein that binds to the regulatory octamer motif
  • Science 1988; 241:577-580
  • Staudt LM, Clerc RG, Singh H, LeBowitz J, Sharp PA, Baltimore D
  • View Abstract on PubMed
  • Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA
  • Cell 1988; 52:415-423
  • Singh H, LeBowitz JH, Baldwin AS Jr., Sharp PA
  • View Abstract on PubMed
  • A lymphoid-specific protein binding to the octamer motif of immunoglobulin genes
  • Nature 1986; 323:640-643
  • Staudt LM, Singh H, Sen R, Wirth T, Sharp PA, Baltimore D
  • View Abstract on PubMed
  • A nuclear factor that binds to a conserved sequence motif in transcriptional control elements of immunoglobulin genes
  • Nature 1986; 319:154-158
  • Singh H, Sen R, Baltimore D, Sharp PA
  • View Abstract on PubMed
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Awards & Honors
  • Chair, Committee on Immunology, The University of Chicago - 2008-2009
  • American Association of Immunologists Distinguished Lecturer, 95th Annual Meeting - 2008
  • Review Panel Member, California Institute of Regenerative Medicine - 2006-2009
  • Chair, Board of Scientific Counselors, National Cancer Institute - 2006-2007
  • Louis Block Professor of Molecular Genetics, The University of Chicago - 2003
  • Member, Board of Scientific Counselors, National Cancer Institute - 2002-2007
  • Editor, Molecular and Cellular Biology - 1997-2007
  • Member of Editorial Board of Molecular and Cellular Biology - 1993-1997
  • Postdoctoral fellowship, The Jane Coffin Childs Memorial Fund for Medical Research - 1984-1987
  • Thapar Gold Medal, Punjab Agricultural University, Outstanding University Undergraduate - 1977
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Ellen Filvaroff, Senior Scientist and Alex Avardo, Receipent of Free Medicine From the Genentech® Access to Care Foundation, on the cover of Genentech's 2006 Annual Report.