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Francois Spitz

TitleProfessor
InstitutionUniversity of Chicago
DepartmentHuman Genetics
AddressChicago IL 60637
Email
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    Collapse Overview 
    Collapse overview
    Our group is interested in understanding how the architecture of the genome contributes to the specificity and robustness of the gene expression programs that govern embryonic development and cell differentiation.
    Vertebrate genomes contain hundreds of thousands of regulatory sequences that can influence the expression of genes sometimes located hundreds of kilobases away. Our main goal is to understand how the folding of the genome in specific domains and dynamic structures contributes to transform such a dispersed information into highly specific regulatory ensembles. We study as well how perturbations of these processes, notably due to chromosomal rearrangements, could lead to developmental or oncogenic pathologies, but may have also participated to animal evolution.


    Collapse Biography 
    Collapse education and training
    Université Pierre et Marie Curie - Paris 6, Paris - FranceDEA09/1993Cellular and Molecular Genetics
    Université Pierre et Marie Curie - Paris 6, Paris - FrancePhD12/1997Cellular and Molecular Genetics
    University of Geneva, Geneva - Switzerland08/2006Developmental Genetics
    Collapse awards and honors
    2016elected member, European Molecular Biology Organisation

    Collapse ORNG Applications 
    Collapse Websites

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Comai GE, Tesarová M, Dupé V, Rhinn M, Vallecillo-García P, da Silva F, Feret B, Exelby K, Dollé P, Carlsson L, Pryce B, Spitz F, Stricker S, Zikmund T, Kaiser J, Briscoe J, Schedl A, Ghyselinck NB, Schweitzer R, Tajbakhsh S. Local retinoic acid signaling directs emergence of the extraocular muscle functional unit. PLoS Biol. 2020 11; 18(11):e3000902. PMID: 33201874.
      View in: PubMed
    2. Spitz F. Chromosomes come together to help mice distinguish odours. Nature. 2019 01; 565(7740):439-440. PMID: 30666054.
      View in: PubMed
    3. Bahr C, von Paleske L, Uslu VV, Remeseiro S, Takayama N, Ng SW, Murison A, Langenfeld K, Petretich M, Scognamiglio R, Zeisberger P, Benk AS, Amit I, Zandstra PW, Lupien M, Dick JE, Trumpp A, Spitz F. Author Correction: A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies. Nature. 2018 06; 558(7711):E4. PMID: 29769714.
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    4. Sebé-Pedrós A, Saudemont B, Chomsky E, Plessier F, Mailhé MP, Renno J, Loe-Mie Y, Lifshitz A, Mukamel Z, Schmutz S, Novault S, Steinmetz PRH, Spitz F, Tanay A, Marlow H. Cnidarian Cell Type Diversity and Regulation Revealed by Whole-Organism Single-Cell RNA-Seq. Cell. 2018 05 31; 173(6):1520-1534.e20. PMID: 29856957.
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    5. Bahr C, von Paleske L, Uslu VV, Remeseiro S, Takayama N, Ng SW, Murison A, Langenfeld K, Petretich M, Scognamiglio R, Zeisberger P, Benk AS, Amit I, Zandstra PW, Lupien M, Dick JE, Trumpp A, Spitz F. A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies. Nature. 2018 01 25; 553(7689):515-520. PMID: 29342133.
      View in: PubMed
    6. Schwarzer W, Abdennur N, Goloborodko A, Pekowska A, Fudenberg G, Loe-Mie Y, Fonseca NA, Huber W, Haering CH, Mirny L, Spitz F. Two independent modes of chromatin organization revealed by cohesin removal. Nature. 2017 11 02; 551(7678):51-56. PMID: 29094699.
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    7. Symmons O, Pan L, Remeseiro S, Aktas T, Klein F, Huber W, Spitz F. The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing the Effects of Genomic Distances. Dev Cell. 2016 12 05; 39(5):529-543. PMID: 27867070.
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    8. Franke M, Ibrahim DM, Andrey G, Schwarzer W, Heinrich V, Schöpflin R, Kraft K, Kempfer R, Jerkovic I, Chan WL, Spielmann M, Timmermann B, Wittler L, Kurth I, Cambiaso P, Zuffardi O, Houge G, Lambie L, Brancati F, Pombo A, Vingron M, Spitz F, Mundlos S. Formation of new chromatin domains determines pathogenicity of genomic duplications. Nature. 2016 Oct 13; 538(7624):265-269. PMID: 27706140.
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    9. Yao Y, Minor PJ, Zhao YT, Jeong Y, Pani AM, King AN, Symmons O, Gan L, Cardoso WV, Spitz F, Lowe CJ, Epstein DJ. Erratum: Cis-regulatory architecture of a brain signaling center predates the origin of chordates. Nat Genet. 2016 07 27; 48(8):970. PMID: 27463400.
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    10. Spitz F. Gene regulation at a distance: From remote enhancers to 3D regulatory ensembles. Semin Cell Dev Biol. 2016 09; 57:57-67. PMID: 27364700.
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    11. Yao Y, Minor PJ, Zhao YT, Jeong Y, Pani AM, King AN, Symmons O, Gan L, Cardoso WV, Spitz F, Lowe CJ, Epstein DJ. Cis-regulatory architecture of a brain signaling center predates the origin of chordates. Nat Genet. 2016 05; 48(5):575-80. PMID: 27064252.
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    12. Remeseiro S, Hörnblad A, Spitz F. Gene regulation during development in the light of topologically associating domains. Wiley Interdiscip Rev Dev Biol. 2016 Mar-Apr; 5(2):169-85. PMID: 26558551.
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    13. Liu X, Tamada K, Kishimoto R, Okubo H, Ise S, Ohta H, Ruf S, Nakatani J, Kohno N, Spitz F, Takumi T. Transcriptome profiling of white adipose tissue in a mouse model for 15q duplication syndrome. Genom Data. 2015 Sep; 5:394-6. PMID: 26484295.
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    14. Kishimoto R, Tamada K, Liu X, Okubo H, Ise S, Ohta H, Ruf S, Nakatani J, Kohno N, Spitz F, Takumi T. Model mice for 15q11-13 duplication syndrome exhibit late-onset obesity and altered lipid metabolism. Hum Mol Genet. 2015 Aug 15; 24(16):4559-72. PMID: 26002101.
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    15. Amin S, Donaldson IJ, Zannino DA, Hensman J, Rattray M, Losa M, Spitz F, Ladam F, Sagerström C, Bobola N. Hoxa2 selectively enhances Meis binding to change a branchial arch ground state. Dev Cell. 2015 Feb 09; 32(3):265-77. PMID: 25640223.
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    16. Tsujimura T, Klein FA, Langenfeld K, Glaser J, Huber W, Spitz F. A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes. PLoS Genet. 2015 Jan; 11(1):e1004897. PMID: 25569170.
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    17. Schwarzer W, Spitz F. The architecture of gene expression: integrating dispersed cis-regulatory modules into coherent regulatory domains. Curr Opin Genet Dev. 2014 Aug; 27:74-82. PMID: 24907448.
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    18. Uslu VV, Petretich M, Ruf S, Langenfeld K, Fonseca NA, Marioni JC, Spitz F. Long-range enhancers regulating Myc expression are required for normal facial morphogenesis. Nat Genet. 2014 Jul; 46(7):753-8. PMID: 24859337.
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    19. Symmons O, Uslu VV, Tsujimura T, Ruf S, Nassari S, Schwarzer W, Ettwiller L, Spitz F. Functional and topological characteristics of mammalian regulatory domains. Genome Res. 2014 Mar; 24(3):390-400. PMID: 24398455.
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    20. Kirchmaier S, Höckendorf B, Möller EK, Bornhorst D, Spitz F, Wittbrodt J. Efficient site-specific transgenesis and enhancer activity tests in medaka using PhiC31 integrase. Development. 2013 Oct; 140(20):4287-95. PMID: 24048591.
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    21. Andrey G, Montavon T, Mascrez B, Gonzalez F, Noordermeer D, Leleu M, Trono D, Spitz F, Duboule D. A switch between topological domains underlies HoxD genes collinearity in mouse limbs. Science. 2013 Jun 07; 340(6137):1234167. PMID: 23744951.
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    22. Symmons O, Spitz F. From remote enhancers to gene regulation: charting the genome's regulatory landscapes. Philos Trans R Soc Lond B Biol Sci. 2013; 368(1620):20120358. PMID: 23650632.
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    23. Chen CK, Symmons O, Uslu VV, Tsujimura T, Ruf S, Smedley D, Spitz F. TRACER: a resource to study the regulatory architecture of the mouse genome. BMC Genomics. 2013 Apr 02; 14:215. PMID: 23547943.
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    24. Marinic M, Aktas T, Ruf S, Spitz F. An integrated holo-enhancer unit defines tissue and gene specificity of the Fgf8 regulatory landscape. Dev Cell. 2013 Mar 11; 24(5):530-42. PMID: 23453598.
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    25. Weischenfeldt J, Symmons O, Spitz F, Korbel JO. Phenotypic impact of genomic structural variation: insights from and for human disease. Nat Rev Genet. 2013 Feb; 14(2):125-38. PMID: 23329113.
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    26. Spitz F, Furlong EE. Transcription factors: from enhancer binding to developmental control. Nat Rev Genet. 2012 Sep; 13(9):613-26. PMID: 22868264.
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    27. Montavon T, Soshnikova N, Mascrez B, Joye E, Thevenet L, Splinter E, de Laat W, Spitz F, Duboule D. A regulatory archipelago controls Hox genes transcription in digits. Cell. 2011 Nov 23; 147(5):1132-45. PMID: 22118467.
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    28. Ruf S, Symmons O, Uslu VV, Dolle D, Hot C, Ettwiller L, Spitz F. Large-scale analysis of the regulatory architecture of the mouse genome with a transposon-associated sensor. Nat Genet. 2011 Mar 20; 43(4):379-86. PMID: 21423180.
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    29. Friedli M, Barde I, Arcangeli M, Verp S, Quazzola A, Zakany J, Lin-Marq N, Robyr D, Attanasio C, Spitz F, Duboule D, Trono D, Antonarakis SE. A systematic enhancer screen using lentivector transgenesis identifies conserved and non-conserved functional elements at the Olig1 and Olig2 locus. PLoS One. 2010 Dec 29; 5(12):e15741. PMID: 21206754.
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    30. Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T, Maillard PV, Layard-Liesching H, Verp S, Marquis J, Spitz F, Constam DB, Trono D. KAP1 controls endogenous retroviruses in embryonic stem cells. Nature. 2010 Jan 14; 463(7278):237-40. PMID: 20075919.
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    31. Spitz F. Control of vertebrate Hox clusters by remote and global cis-acting regulatory sequences. Adv Exp Med Biol. 2010; 689:63-78. PMID: 20795322.
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    32. Tschopp P, Tarchini B, Spitz F, Zakany J, Duboule D. Uncoupling time and space in the collinear regulation of Hox genes. PLoS Genet. 2009 Mar; 5(3):e1000398. PMID: 19266017.
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    33. Ettwiller L, Budd A, Spitz F, Wittbrodt J. Analysis of mammalian gene batteries reveals both stable ancestral cores and highly dynamic regulatory sequences. Genome Biol. 2008; 9(12):R172. PMID: 19087242.
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    34. Sauvain MO, Dorr AP, Stevenson B, Quazzola A, Naef F, Wiznerowicz M, Schütz F, Jongeneel V, Duboule D, Spitz F, Trono D. Genotypic features of lentivirus transgenic mice. J Virol. 2008 Jul; 82(14):7111-9. PMID: 18463153.
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    35. Friedli M, Nikolaev S, Lyle R, Arcangeli M, Duboule D, Spitz F, Antonarakis SE. Characterization of mouse Dactylaplasia mutations: a model for human ectrodactyly SHFM3. Mamm Genome. 2008 Apr; 19(4):272-8. PMID: 18392654.
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    36. Spitz F, Duboule D. Global control regions and regulatory landscapes in vertebrate development and evolution. Adv Genet. 2008; 61:175-205. PMID: 18282506.
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    37. Gonzalez F, Duboule D, Spitz F. Transgenic analysis of Hoxd gene regulation during digit development. Dev Biol. 2007 Jun 15; 306(2):847-59. PMID: 17448461.
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    38. Spitz F, Furlong EE. Genomics and development: Taking developmental biology to new heights. Dev Cell. 2006 Oct; 11(4):451-7. PMID: 17051688.
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    39. Spitz F, Herkenne C, Hinard C, Duboule D. [A STRING lifts the veil on the mechanisms controlling Hox genes expression]. Med Sci (Paris). 2006 Jan; 22(1):14-6. PMID: 16386210.
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    40. Spitz F, Herkenne C, Morris MA, Duboule D. Inversion-induced disruption of the Hoxd cluster leads to the partition of regulatory landscapes. Nat Genet. 2005 Aug; 37(8):889-93. PMID: 15995706.
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    41. Spitz F, Duboule D. Developmental biology: reproduction in clusters. Nature. 2005 Apr 07; 434(7034):715-6. PMID: 15815616.
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    42. Grifone R, Laclef C, Spitz F, Lopez S, Demignon J, Guidotti JE, Kawakami K, Xu PX, Kelly R, Petrof BJ, Daegelen D, Concordet JP, Maire P. Six1 and Eya1 expression can reprogram adult muscle from the slow-twitch phenotype into the fast-twitch phenotype. Mol Cell Biol. 2004 Jul; 24(14):6253-67. PMID: 15226428.
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    43. Zuniga A, Michos O, Spitz F, Haramis AP, Panman L, Galli A, Vintersten K, Klasen C, Mansfield W, Kuc S, Duboule D, Dono R, Zeller R. Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression. Genes Dev. 2004 Jul 01; 18(13):1553-64. PMID: 15198975.
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    44. Spitz F, Gonzalez F, Duboule D. A global control region defines a chromosomal regulatory landscape containing the HoxD cluster. Cell. 2003 May 02; 113(3):405-17. PMID: 12732147.
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    45. Spitz F, Benbacer L, Sabourin JC, Salminen M, Chen F, Cywiner C, Kahn A, Chatelet F, Maire P, Daegelen D. Fiber-type specific and position-dependent expression of a transgene in limb muscles. Differentiation. 2002 Oct; 70(8):457-67. PMID: 12366383.
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    46. Spitz F, Montavon T, Monso-Hinard C, Morris M, Ventruto ML, Antonarakis S, Ventruto V, Duboule D. A t(2;8) balanced translocation with breakpoints near the human HOXD complex causes mesomelic dysplasia and vertebral defects. Genomics. 2002 Apr; 79(4):493-8. PMID: 11944980.
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    47. Spitz F, Gonzalez F, Peichel C, Vogt TF, Duboule D, Zákány J. Large scale transgenic and cluster deletion analysis of the HoxD complex separate an ancestral regulatory module from evolutionary innovations. Genes Dev. 2001 Sep 01; 15(17):2209-14. PMID: 11544178.
      View in: PubMed
    48. Tada H, Maron DJ, Choi EA, Barsoum J, Lei H, Xie Q, Liu W, Ellis L, Moscioni AD, Tazelaar J, Fawell S, Qin X, Propert KJ, Davis A, Fraker DL, Wilson JM, Spitz FR. Systemic IFN-beta gene therapy results in long-term survival in mice with established colorectal liver metastases. J Clin Invest. 2001 Jul; 108(1):83-95. PMID: 11435460.
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    49. Bauer TW, Hahn SM, Spitz FR, Kachur A, Glatstein E, Fraker DL. Preliminary report of photodynamic therapy for intraperitoneal sarcomatosis. Ann Surg Oncol. 2001 Apr; 8(3):254-9. PMID: 11314943.
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    50. Hendren SK, Hahn SM, Spitz FR, Bauer TW, Rubin SC, Zhu T, Glatstein E, Fraker DL. Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Ann Surg Oncol. 2001 Jan-Feb; 8(1):65-71. PMID: 11206227.
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    51. Fan X, Brass LF, Poncz M, Spitz F, Maire P, Manning DR. The alpha subunits of Gz and Gi interact with the eyes absent transcription cofactor Eya2, preventing its interaction with the six class of homeodomain-containing proteins. J Biol Chem. 2000 Oct 13; 275(41):32129-34. PMID: 10906137.
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    52. Bedrosian I, Faries MB, Guerry D, Elenitsas R, Schuchter L, Mick R, Spitz FR, Bucky LP, Alavi A, Elder DE, Fraker DL, Czerniecki BJ. Incidence of sentinel node metastasis in patients with thin primary melanoma (< or = 1 mm) with vertical growth phase. Ann Surg Oncol. 2000 May; 7(4):262-7. PMID: 10819365.
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    53. Bedrosian I, Scheff AM, Mick R, Callans LS, Bucky LP, Spitz FR, Helsabeck C, Elder DE, Alavi A, Fraker DF, Czerniecki BJ. 99mTc-human serum albumin: an effective radiotracer for identifying sentinel lymph nodes in melanoma. J Nucl Med. 1999 Jul; 40(7):1143-8. PMID: 10405134.
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    54. Spitz F, Demignon J, Kahn A, Daegelen D, Maire P. Developmental regulation of the aldolase A muscle-specific promoter during in vivo muscle maturation is controlled by a nuclear receptor binding element. J Mol Biol. 1999 Jun 18; 289(4):893-903. PMID: 10369770.
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    55. Czerniecki BJ, Scheff AM, Callans LS, Spitz FR, Bedrosian I, Conant EF, Orel SG, Berlin J, Helsabeck C, Fraker DL, Reynolds C. Immunohistochemistry with pancytokeratins improves the sensitivity of sentinel lymph node biopsy in patients with breast carcinoma. Cancer. 1999 Mar 01; 85(5):1098-103. PMID: 10091794.
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    56. Spitz F, Demignon J, Porteu A, Kahn A, Concordet JP, Daegelen D, Maire P. Expression of myogenin during embryogenesis is controlled by Six/sine oculis homeoproteins through a conserved MEF3 binding site. Proc Natl Acad Sci U S A. 1998 Nov 24; 95(24):14220-5. PMID: 9826681.
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    57. Bauer TW, Spitz FR. Adjuvant and neoadjuvant chemoradiation therapy for primary colorectal cancer. Surg Oncol. 1998 Nov-Dec; 7(3-4):175-81. PMID: 10677168.
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