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
  • Šale S, Lafkas D, Artavanis-Tsakonas S. Notch2 genetic fate mapping reveals two previously unrecognized mammary epithelial lineages. Nat Cell Biol 2013. 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
  • 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
  • Artavanis-Tsakonas S, Muskavitch MA. Notch: the past, the present, and the future. Curr Top Dev Biol 2010; 92:1-29. 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
  • Fre S, Pallavi SK, Huyghe M, Laé 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
  • 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
  • Fleming RJ, Purcell K, Artavanis-Tsakonas S. The NOTCH receptor and its ligands. Trends Cell Biol 2007; 7:437-41. PubMed
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