Photo of David L. Van Vactor,  PhD

David L. Van Vactor, PhD

Harvard Medical School

Harvard Medical School
Phone: (617) 432-2195
Fax: (617) 432-2808


Davie@hms.harvard.edu

David L. Van Vactor, PhD

Harvard Medical School

EDUCATIONAL TITLES

  • Professor, Cell Biology, Harvard Medical School
  • Director, Biological and Biomedical Sciences Program, Harvard Medical School

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research goal is to understand fundamental mechanisms that guide neuronal processes to correct targets within the developing nervous system. We have used Drosophila genetics to define signaling pathways, from cell surface to cytoskeleton, that growth cones use to accurately interpret guidance information and execute directional axon outgrowth. Our recent work on the receptor protein-tyrosine phosphatase Dlar suggests that motor axon guidance behavior is controlled by a antagonistic balance of tyrosine kinase and phosphatase activity involving the proto-oncogene Abl and other proteins in the Abl pathway that act to control cytoskeletal dynamics. Our current analysis suggests that Enabled, Profilin and CAP collaborate with Abl during axonogenesis. Exactly how extracellular information regulates this process, and how tyrosine phosphorylation influences the activities of the downstream players, is currently under investigation. We anticipate that these studies will provide insights valuable for the understanding of cell motility in a variety of contexts, including cancer cell metastasis.

Publications

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  • Mugat B, Akkouche A, Serrano V, Armenise C, Li B, Brun C, Fulga TA, Van Vactor D, Pélisson A, Chambeyron S. MicroRNA-Dependent Transcriptional Silencing of Transposable Elements in Drosophila Follicle Cells. PLoS Genet. 2015; 11:e1005194. PubMed
  • Fulga TA, McNeill EM, Binari R, Yelick J, Blanche A, Booker M, Steinkraus BR, Schnall-Levin M, Zhao Y, DeLuca T, Bejarano F, Han Z, Lai EC, Wall DP, Perrimon N, Van Vactor D. A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs. Nat Commun 2015; 6:7279. PubMed
  • Guarani V, McNeill EM, Paulo JA, Huttlin EL, Fröhlich F, Gygi SP, Van Vactor D, Harper JW. QIL1 is a novel mitochondrial protein required for MICOS complex stability and cristae morphology. Elife 2015. PubMed
  • Lu CS, Zhai B, Mauss A, Landgraf M, Gygi S, Van Vactor D. MicroRNA-8 promotes robust motor axon targeting by coordinate regulation of cell adhesion molecules during synapse development. Philos Trans R Soc Lond B Biol Sci 2014. PubMed
  • Marler KJ, Suetterlin P, Dopplapudi A, Rubikaite A, Adnan J, Maiorano NA, Lowe AS, Thompson ID, Pathania M, Bordey A, Fulga T, Van Vactor DL, Hindges R, Drescher U. BDNF promotes axon branching of retinal ganglion cells via miRNA-132 and p250GAP. J Neurosci 2014; 34:969-79. PubMed
  • Berke B, Wittnam J, McNeill E, Van Vactor DL, Keshishian H. Retrograde BMP signaling at the synapse: a permissive signal for synapse maturation and activity-dependent plasticity. J Neurosci 2013; 33:17937-50. PubMed
  • Long JB, Van Vactor D. Embryonic and larval neural connectivity: progressive changes in synapse form and function at the neuromuscular junction mediated by cytoskeletal regulation. Wiley Interdiscip Rev Dev Biol 2013; 2:747-65. PubMed
  • Walker JA, Gouzi JY, Long JB, Huang S, Maher RC, Xia H, Khalil K, Ray A, Van Vactor D, Bernards R, Bernards A. Genetic and functional studies implicate synaptic overgrowth and ring gland cAMP/PKA signaling defects in the Drosophila melanogaster neurofibromatosis-1 growth deficiency. PLoS Genet. 2013; 9:e1003958. PubMed
  • Lowery LA, Stout A, Faris AE, Ding L, Baird MA, Davidson MW, Danuser G, Van Vactor D. Growth cone-specific functions of XMAP215 in restricting microtubule dynamics and promoting axonal outgrowth. Neural Develop 2013; 8:22. PubMed
  • Bejarano F, Bortolamiol-Becet D, Dai Q, Sun K, Saj A, Chou YT, Raleigh DR, Kim K, Ni JQ, Duan H, Yang JS, Fulga TA, Van Vactor D, Perrimon N, Lai EC. A genome-wide transgenic resource for conditional expression of Drosophila microRNAs. Development 2012; 139:2821-31. 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
  • Lowery LA, Lee H, Lu C, Murphy R, Obar RA, Zhai B, Schedl M, Van Vactor D, Zhan Y. Parallel Genetic and Proteomic Screens Identify Msps as a CLASP-Abl Pathway Interactor in Drosophila. Genetics 2010; 185:1311-25. PubMed
  • Loya CM, Van Vactor D, Fulga TA. Understanding neuronal connectivity through the post-transcriptional toolkit. Genes Dev 2010; 24:625-35. PubMed
  • Prakash S, McLendon HM, Dubreuil CI, Ghose A, Hwa J, Dennehy KA, Tomalty KM, Clark KL, Van Vactor D, Clandinin TR. Complex interactions amongst N-cadherin, DLAR, and Liprin-alpha regulate Drosophila photoreceptor axon targeting. Dev Biol 2009; 336:10-9. PubMed
  • Loya CM, Lu CS, Van Vactor D, Fulga TA. Transgenic microRNA inhibition with spatiotemporal specificity in intact organisms. Nat Methods 2009; 6:897-903. PubMed
  • Lowery LA, Van Vactor D. The trip of the tip: understanding the growth cone machinery. Nat Rev Mol Cell Biol 2009; 10:332-43. PubMed
  • Fulga TA, Van Vactor D. Synapses and growth cones on two sides of a highwire. Neuron 2008; 57:339-44. PubMed
  • Tsai PI, Kao HH, Grabbe C, Lee YT, Ghose A, Lai TT, Peng KP, Van Vactor D, Palmer RH, Chen RH, Yeh SR, Chien CT. Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth. Neural Develop 2008; 3:26. PubMed
  • Lu CS, Van Vactor D. Synapse specificity: Wnts keep motor axons on target. Curr Biol 2007; 17:R895-8. PubMed
  • Gates J, Mahaffey JP, Rogers SL, Emerson M, Rogers EM, Sottile SL, Van Vactor D, Gertler FB, Peifer M. Enabled plays key roles in embryonic epithelial morphogenesis in Drosophila. Development 2007; 134:2027-39. PubMed
  • Takai Y, Matikainen T, Jurisicova A, Kim MR, Trbovich AM, Fujita E, Nakagawa T, Lemmers B, Flavell RA, Hakem R, Momoi T, Yuan J, Tilly JL, Perez GI. Caspase-12 compensates for lack of caspase-2 and caspase-3 in female germ cells. Apoptosis 2007; 12:791-800. PubMed
  • Johnson KG, Tenney AP, Ghose A, Duckworth AM, Higashi ME, Parfitt K, Marcu O, Heslip TR, Marsh JL, Schwarz TL, Flanagan JG, Van Vactor D. The HSPGs Syndecan and Dallylike bind the receptor phosphatase LAR and exert distinct effects on synaptic development. Neuron 2006; 49:517-31. PubMed
  • Lee H, Engel U, Rusch J, Scherrer S, Sheard K, Van Vactor D. The microtubule plus end tracking protein Orbit/MAST/CLASP acts downstream of the tyrosine kinase Abl in mediating axon guidance. Neuron 2004; 42:913-26. PubMed
  • Johnson KG, Ghose A, Epstein E, Lincecum J, O'Connor MB, Van Vactor D. Axonal heparan sulfate proteoglycans regulate the distribution and efficiency of the repellent slit during midline axon guidance. Curr Biol 2004; 14:499-504. PubMed
  • Wills Z, Emerson M, Rusch J, Bikoff J, Baum B, Perrimon N, Van Vactor D. A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding. Neuron 2002; 36:611-22. PubMed
  • Van Vactor D, Flanagan JG. The middle and the end: slit brings guidance and branching together in axon pathway selection. Neuron 1999; 22:649-52. PubMed
  • Wills Z, Bateman J, Korey CA, Comer A, Van Vactor D. The tyrosine kinase Abl and its substrate enabled collaborate with the receptor phosphatase Dlar to control motor axon guidance. Neuron 1999; 22:301-12. PubMed
  • Flanagan JG, Van Vactor D. Through the looking glass: axon guidance at the midline choice point. Cell 1998; 92:429-32. PubMed
  • Van Vactor D, O'Reilly AM, Neel BG. Genetic analysis of protein tyrosine phosphatases. Curr Opin Genet Dev 1998; 8:112-26. PubMed
  • Kaufmann N, Wills ZP, Van Vactor D. Drosophila Rac1 controls motor axon guidance. Development 1998; 125:453-61. PubMed
  • Krueger NX, Van Vactor D, Wan HI, Gelbart WM, Goodman CS, Saito H. The transmembrane tyrosine phosphatase DLAR controls motor axon guidance in Drosophila. Cell 1996; 84:611-22. PubMed
  • Hart AC, Harrison SD, Van Vactor DL, Rubin GM, Zipursky SL. The interaction of bride of sevenless with sevenless is conserved between Drosophila virilis and Drosophila melanogaster. Proc Natl Acad Sci U S A 1993; 90:5047-51. PubMed
  • Van Vactor DL, Cagan RL, Kr. Induction in the developing compound eye of Drosophila: multiple mechanisms restrict R7 induction to a single retinal precursor cell. Cell 1991; 67:1145-55. PubMed
  • Hart AC, Kr. Induction of cell fate in the Drosophila retina: the bride of sevenless protein is predicted to contain a large extracellular domain and seven transmembrane segments. Genes Dev 1990; 4:1835-47. PubMed
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