Photo of Spyridon Artavanis-Tsakonas,  PhD

Spyridon Artavanis-Tsakonas, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-7048
Fax: (617) 432-7050


artavanis@hms.harvard.edu

Spyridon Artavanis-Tsakonas, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Professor, Cell Biology, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

We are interested in the mechanisms that control cell fates during development and pathogenesis. We have been focusing our attention on the Notch signaling pathway. Notch signaling defines an evolutionary ancient cell interaction mechanism, which plans a fundamental role in metazoan development. Signals exchange between neighboring cells through the Notch receptor can amplify and consolidate molecular differences, which eventually dictate cell fates. Thus Notch signals control how cells respond to intrinsic or extrinsic developmental cues that are necessary to unfold specific developmental programs. Notch signal modulation was shown to affect the implementation of differentiation, proliferation and apoptotic programs, providing a general developmental tool to influence organ formation and morphogenesis. We have been exploring the molecular biology of notch signaling and its involvement two known human syndromes as well as the onset and maintenance of neoplastic fate.

Publications

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  • Rhee DY, Cho DY, Zhai B, Slattery M, Ma L, Mintseris J, Wong CY, White KP, Celniker SE, Przytycka TM, Gygi SP, Obar RA, Artavanis-Tsakonas S. Transcription Factor Networks in Drosophila melanogaster. Cell Rep 2014; 8:2031-43. PubMed
  • Hori K, Sen A, Artavanis-Tsakonas S. Genetic circuitry modulating notch signals through endosomal trafficking. Methods Enzymol 2013; 534:283-99. PubMed
  • Oh P, Lobry C, Gao J, Tikhonova A, Loizou E, Manent J, Manet J, van Handel B, Ibrahim S, Greve J, Mikkola H, Artavanis-Tsakonas S, Aifantis I. In vivo mapping of notch pathway activity in normal and stress hematopoiesis. Cell Stem Cell 2013; 13:190-204. PubMed
  • Hori K, Sen A, Artavanis-Tsakonas S. Notch signaling at a glance. J Cell Sci 2013; 126:2135-40. PubMed
  • Fleming RJ, Hori K, Sen A, Filloramo GV, Langer JM, Obar RA, Artavanis-Tsakonas S, Maharaj-Best AC. An extracellular region of Serrate is essential for ligand-induced cis-inhibition of Notch signaling. Development 2013; 140:2039-49. PubMed
  • Sale S, Lafkas D, Artavanis-Tsakonas S. Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages. Nat Cell Biol 2013. PubMed
  • Hori K, Sen A, Kirchhausen T, Artavanis-Tsakonas S. Regulation of ligand-independent Notch signal through intracellular trafficking. Commun Integr Biol 2012; 5:374-6. PubMed
  • Pallavi SK, Ho DM, Hicks C, Miele L, Artavanis-Tsakonas S. Notch and Mef2 synergize to promote proliferation and metastasis through JNK signal activation in Drosophila. EMBO J 2012; 31:2895-907. PubMed
  • Sun Y, Klauzinska M, Lake RJ, Lee JM, Santopietro S, Raafat A, Salomon D, Callahan R, Artavanis-Tsakonas S. Trp53 regulates Notch 4 signaling through Mdm2. J Cell Sci 2011; 124:1067-76. PubMed
  • Dimitriadi M, Sleigh JN, Walker A, Chang HC, Sen A, Kalloo G, Harris J, Barsby T, Walsh MB, Satterlee JS, Li C, Van Vactor D, Artavanis-Tsakonas S, Hart AC. Conserved genes act as modifiers of invertebrate SMN loss of function defects. PLoS Genet. 2010; 6:e1001172. PubMed
  • Mazzone M, Selfors LM, Albeck J, Overholtzer M, Sale S, Carroll DL, Pandya D, Lu Y, Mills GB, Aster JC, Artavanis-Tsakonas S, Brugge JS. Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells. Proc Natl Acad Sci U S A 2010; 107:5012-7. PubMed
  • Kelly DF, Lake RJ, Middelkoop TC, Fan HY, Artavanis-Tsakonas S, Walz T. Molecular structure and dimeric organization of the Notch extracellular domain as revealed by electron microscopy. PLoS ONE 2010; 5:e10532. PubMed
  • Artavanis-Tsakonas S, Muskavitch MA. Notch: the past, the present, and the future. Curr Top Dev Biol 2010; 92:1-29. PubMed
  • Fre S, Pallavi SK, Huyghe M, LaĆ© M, Janssen KP, Robine S, Artavanis-Tsakonas S, Louvard D. Notch and Wnt signals cooperatively control cell proliferation and tumorigenesis in the intestine. Proc Natl Acad Sci U S A 2009; 106:6309-14. PubMed
  • Hurlbut GD, Kankel MW, Artavanis-Tsakonas S. Nodal points and complexity of Notch-Ras signal integration. Proc Natl Acad Sci U S A 2009; 106:2218-23. PubMed
  • Lake RJ, Grimm LM, Veraksa A, Banos A, Artavanis-Tsakonas S. In vivo analysis of the Notch receptor S1 cleavage. PLoS ONE 2009; 4:e6728. PubMed
  • Kankel MW, Hurlbut GD, Upadhyay G, Yajnik V, Yedvobnick B, Artavanis-Tsakonas S. Investigating the genetic circuitry of mastermind in Drosophila, a notch signal effector. Genetics 2007; 177:2493-505. PubMed
  • Kelly DF, Lake RJ, Walz T, Artavanis-Tsakonas S. Conformational variability of the intracellular domain of Drosophila Notch and its interaction with Suppressor of Hairless. Proc Natl Acad Sci U S A 2007; 104:9591-6. PubMed
  • Hurlbut GD, Kankel MW, Lake RJ, Artavanis-Tsakonas S. Crossing paths with Notch in the hyper-network. Curr Opin Cell Biol 2007; 19:166-75. PubMed
  • Klinakis A, Szabolcs M, Politi K, Kiaris H, Artavanis-Tsakonas S, Efstratiadis A. Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice. Proc Natl Acad Sci U S A 2006; 103:9262-7. PubMed
  • Louvi A, Artavanis-Tsakonas S. Notch signalling in vertebrate neural development. Nat Rev Neurosci 2006; 7:93-102. PubMed
  • Mourikis P, Hurlbut GD, Artavanis-Tsakonas S. Enigma, a mitochondrial protein affecting lifespan and oxidative stress response in Drosophila. Proc Natl Acad Sci U S A 2006; 103:1307-12. PubMed
  • Louvi A, Arboleda-Velasquez JF, Artavanis-Tsakonas S. CADASIL: a critical look at a Notch disease. Dev Neurosci 2006; 28:5-12. PubMed
  • Mukherjee A, Veraksa A, Bauer A, Rosse C, Camonis J, Artavanis-Tsakonas S. Regulation of Notch signalling by non-visual beta-arrestin. Nat Cell Biol 2005; 7:1091-101. PubMed
  • Fre S, Huyghe M, Mourikis P, Robine S, Louvard D, Artavanis-Tsakonas S. Notch signals control the fate of immature progenitor cells in the intestine. Nature 2005; 435:964-8. PubMed
  • Veraksa A, Bauer A, Artavanis-Tsakonas S. Analyzing protein complexes in Drosophila with tandem affinity purification-mass spectrometry. Dev Dyn 2005; 232:827-34. PubMed
  • Kiaris H, Politi K, Grimm LM, Szabolcs M, Fisher P, Efstratiadis A, Artavanis-Tsakonas S. Modulation of notch signaling elicits signature tumors and inhibits hras1-induced oncogenesis in the mouse mammary epithelium. Am J Pathol 2004; 165:695-705. PubMed
  • Moberg KH, Mukherjee A, Veraksa A, Artavanis-Tsakonas S, Hariharan IK. The Drosophila F box protein archipelago regulates dMyc protein levels in vivo. Curr Biol 2004; 14:965-74. PubMed
  • Artavanis-Tsakonas S. Accessing the Exelixis collection. Nat Genet 2004; 36:207. PubMed
  • Grandbarbe L, Bouissac J, Rand M, Hrab. Delta-Notch signaling controls the generation of neurons/glia from neural stem cells in a stepwise process. Development 2003; 130:1391-402. PubMed
  • Beltran S, Blanco E, Serras F, P. Transcriptional network controlled by the trithorax-group gene ash2 in Drosophila melanogaster. Proc Natl Acad Sci U S A 2003; 100:3293-8. PubMed
  • Mishra-Gorur K, Rand MD, Perez-Villamil B, Artavanis-Tsakonas S. Down-regulation of Delta by proteolytic processing. J Cell Biol 2002; 159:313-24. PubMed
  • Matsuno K, Ito M, Hori K, Miyashita F, Suzuki S, Kishi N, Artavanis-Tsakonas S, Okano H. Involvement of a proline-rich motif and RING-H2 finger of Deltex in the regulation of Notch signaling. Development 2002; 129:1049-59. PubMed
  • Kiaris H, Schally AV, Busto R, Halmos G, Artavanis-Tsakonas S, Varga JL. Expression of a splice variant of the receptor for GHRH in 3T3 fibroblasts activates cell proliferation responses to GHRH analogs. Proc Natl Acad Sci U S A 2002; 99:196-200. PubMed
  • Kishi N, Tang Z, Maeda Y, Hirai A, Mo R, Ito M, Suzuki S, Nakao K, Kinoshita T, Kadesch T, Hui C, Artavanis-Tsakonas S, Okano H, Matsuno K. Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis. Int J Dev Neurosci 2001; 19:21-35. PubMed
  • Wu L, Aster JC, Blacklow SC, Lake R, Artavanis-Tsakonas S, Griffin JD. MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors. Nat Genet 2000; 26:484-9. PubMed
  • Rand MD, Grimm LM, Artavanis-Tsakonas S, Patriub V, Blacklow SC, Sklar J, Aster JC. Calcium depletion dissociates and activates heterodimeric notch receptors. Mol Cell Biol 2000; 20:1825-35. PubMed
  • Kurata S, Go MJ, Artavanis-Tsakonas S, Gehring WJ. Notch signaling and the determination of appendage identity. Proc Natl Acad Sci U S A 2000; 97:2117-22. PubMed
  • Guruharsha KG, Obar RA, Mintseris J, Aishwarya K, Krishnan RT, Vijayraghavan K, Artavanis-Tsakonas S. Drosophila protein interaction map (DPiM): a paradigm for metazoan protein complex interactions. Fly (Austin) 2012; 6:246-53. PubMed
  • Gray GE, Mann RS, Mitsiadis E, Henrique D, Carcangiu ML, Banks A, Leiman J, Ward D, Ish-Horowitz D, Artavanis-Tsakonas S. Human ligands of the Notch receptor. Am J Pathol 1999; 154:785-94. PubMed
  • Qi H, Rand MD, Wu X, Sestan N, Wang W, Rakic P, Xu T, Artavanis-Tsakonas S. Processing of the notch ligand delta by the metalloprotease Kuzbanian. Science 1999; 283:91-4. PubMed
  • Go MJ, Artavanis-Tsakonas S. A genetic screen for novel components of the notch signaling pathway during Drosophila bristle development. Genetics 1998; 150:211-20. PubMed
  • Varnum-Finney B, Purton LE, Yu M, Brashem-Stein C, Flowers D, Staats S, Moore KA, Le Roux I, Mann R, Gray G, Artavanis-Tsakonas S, Bernstein ID. The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells. Blood 1998; 91:4084-91. PubMed
  • Matsuno K, Eastman D, Mitsiades T, Quinn AM, Carcanciu ML, Ordentlich P, Kadesch T, Artavanis-Tsakonas S. Human deltex is a conserved regulator of Notch signalling. Nat Genet 1998; 19:74-8. PubMed
  • Ordentlich P, Lin A, Shen CP, Blaumueller C, Matsuno K, Artavanis-Tsakonas S, Kadesch T. Notch inhibition of E47 supports the existence of a novel signaling pathway. Mol Cell Biol 1998; 18:2230-9. PubMed
  • Capobianco AJ, Zagouras P, Blaumueller CM, Artavanis-Tsakonas S, Bishop JM. Neoplastic transformation by truncated alleles of human NOTCH1/TAN1 and NOTCH2. Mol Cell Biol 1997; 17:6265-73. PubMed
  • Fleming RJ, Purcell K, Artavanis-Tsakonas S. The NOTCH receptor and its ligands. Trends Cell Biol 2007; 7:437-41. PubMed
  • Matsuno K, Go MJ, Sun X, Eastman DS, Artavanis-Tsakonas S. Suppressor of Hairless-independent events in Notch signaling imply novel pathway elements. Development 1997; 124:4265-73. PubMed
  • Sun X, Artavanis-Tsakonas S. Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila. Development 1997; 124:3439-48. PubMed
  • Frankel S, Sigel EA, Craig C, Elgin SC, Mooseker MS, Artavanis-Tsakonas S. An actin-related protein in Drosophila colocalizes with heterochromatin protein 1 in pericentric heterochromatin. J Cell Sci 1997; 110 ( Pt 17):1999-2012. PubMed
  • Blaumueller CM, Qi H, Zagouras P, Artavanis-Tsakonas S. Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane. Cell 1997; 90:281-91. PubMed
  • Artavanis-Tsakonas S. Alagille syndrome--a notch up for the Notch receptor. Nat Genet 1997; 16:212-3. PubMed
  • Blaumueller CM, Artavanis-Tsakonas S. Comparative aspects of Notch signaling in lower and higher eukaryotes. Perspect Dev Neurobiol 1997; 4:325-43. PubMed
  • Verheyen EM, Purcell KJ, Fortini ME, Artavanis-Tsakonas S. Analysis of dominant enhancers and suppressors of activated Notch in Drosophila. Genetics 1996; 144:1127-41. PubMed
  • Sun X, Artavanis-Tsakonas S. The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands. Development 1996; 122:2465-74. PubMed
  • Axelrod JD, Matsuno K, Artavanis-Tsakonas S, Perrimon N. Interaction between Wingless and Notch signaling pathways mediated by dishevelled. Science 1996; 271:1826-32. PubMed
  • Liu Y, Dehni G, Purcell KJ, Sokolow J, Carcangiu ML, Artavanis-Tsakonas S, Stifani S. Epithelial expression and chromosomal location of human TLE genes: implications for notch signaling and neoplasia. Genomics 1996; 31:58-64. PubMed
  • Ahmad I, Zaqouras P, Artavanis-Tsakonas S. Involvement of Notch-1 in mammalian retinal neurogenesis: association of Notch-1 activity with both immature and terminally differentiated cells. Mech Dev 1995; 53:73-85. PubMed
  • Zagouras P, Stifani S, Blaumueller CM, Carcangiu ML, Artavanis-Tsakonas S. Alterations in Notch signaling in neoplastic lesions of the human cervix. Proc Natl Acad Sci U S A 1995; 92:6414-8. PubMed
  • Dawson IA, Roth S, Artavanis-Tsakonas S. The Drosophila cell cycle gene fizzy is required for normal degradation of cyclins A and B during mitosis and has homology to the CDC20 gene of Saccharomyces cerevisiae. J Cell Biol 1995; 129:725-37. PubMed
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