Honors & Awards

  • NMSS Postdoctoral Fellowship, National Multiple Sclerosis Society (2015-2017)
  • NRSA Postdoctoral Fellowship, NINDS (2015)
  • Neonatology and Developmental Biology Postdoctoral Training Grant, Stanford / NICHD (2014)
  • Saul Winegrad Award for Outstanding Thesis in Neurosciences, UPenn (2014)
  • NRSA Predoctoral Fellowship, NINDS (2011-2013)
  • System and Integrative Biology Predoctoral Training Grant, UPenn / NIGMS (2007-2009)
  • Robert L. Noland Leadership Award, Caltech (2006)
  • Summer Undergraduate Research Fellowships, Caltech (2003-2005)
  • National Merit Scholarship, National Merit Scholarship Corporation (2002)
  • Third Place Award, Gerontology, Intel International Science and Engineering Fair (2002)

Professional Education

  • Bachelor of Science, California Institute of Technology (2006)
  • Doctor of Philosophy, University of Pennsylvania (2013)

Stanford Advisors

Current Research and Scholarly Interests

mRNA transport and local translation in oligodendrocytes

Microtubule organization in oligodendrocytes

All Publications

  • Dynein/dynactin is necessary for anterograde transport of Mbp mRNA in oligodendrocytes and for myelination in vivo PNAS Herbert, A. L., Fu, M., Drerup, C. M., Gray, R. S., Harty, B. L., Ackerman, S. D., O'Reilly-Pol, T., Johnson, S. L., Nechiporuk, A. V., Barres, B. A., Monk, K. R. 2017; 114 (43): E9153-E9162
  • CNS Myelin Wrapping Is Driven by Actin Disassembly DEVELOPMENTAL CELL Zuchero, J. B., Fu, M., Sloan, S. A., Ibrahim, A., Olson, A., Zaremba, A., Dugas, J. C., Wienbar, S., Caprariello, A. V., Kantor, C., Leonoudakus, D., Lariosa-Willingham, K., Kronenberg, G., Gertz, K., Soderling, S. H., Miller, R. H., Barres, B. A. 2015; 34 (2): 152-167


    Myelin is essential in vertebrates for the rapid propagation of action potentials, but the molecular mechanisms driving its formation remain largely unknown. Here we show that the initial stage of process extension and axon ensheathment by oligodendrocytes requires dynamic actin filament assembly by the Arp2/3 complex. Unexpectedly, subsequent myelin wrapping coincides with the upregulation of actin disassembly proteins and rapid disassembly of the oligodendrocyte actin cytoskeleton and does not require Arp2/3. Inducing loss of actin filaments drives oligodendrocyte membrane spreading and myelin wrapping in vivo, and the actin disassembly factor gelsolin is required for normal wrapping. We show that myelin basic protein, a protein essential for CNS myelin wrapping whose role has been unclear, is required for actin disassembly, and its loss phenocopies loss of actin disassembly proteins. Together, these findings provide insight into the molecular mechanism of myelin wrapping and identify it as an actin-independent form of mammalian cell motility.

    View details for DOI 10.1016/j.devcel.2015.06.011

    View details for Web of Science ID 000358599400007

    View details for PubMedCentralID PMC4519368

  • MAPK8IP1/JIP1 regulates the trafficking of autophagosomes in neurons. Autophagy Fu, M., Holzbaur, E. L. 2014; 10 (11): 2079-2081


    Autophagy is a spatially regulated process in axons; autophagosomes form preferentially in the distal axon tip then move actively and processively toward the cell body. Despite the primarily unidirectional transport observed in live-cell imaging experiments, both anterograde-directed KIF5/kinesin-1 motors and retrograde-directed dynein motors are tightly associated with axonal autophagosomes. Here, we discuss our recent work identifying the scaffolding protein MAPK8IP1/JIP1 (mitogen-activated protein kinase 8 interacting protein 1) as a key regulator of autophagosome transport in neurons. MAPK8IP1 tightly coordinates motor activity to ensure the fidelity of retrograde autophagosome transport in the axon.

    View details for DOI 10.4161/auto.34451

    View details for PubMedID 25483967

  • Integrated regulation of motor-driven organelle transport by scaffolding proteins TRENDS IN CELL BIOLOGY Fu, M., Holzbaur, E. L. 2014; 24 (10): 564-574


    Intracellular trafficking pathways, including endocytosis, autophagy, and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs (trafficking kinesin-binding protein), JIP1, JIP3 (JNK-interacting proteins), huntingtin, and Hook1, interact with molecular motors to coordinate activity and sustain unidirectional transport. Scaffolding proteins also bind to upstream regulatory proteins, including kinases and GTPases, to modulate transport in the cell. This integration of regulatory control with motor activity allows for cargo-specific changes in the transport or targeting of organelles in response to cues from the complex cellular environment.

    View details for DOI 10.1016/j.tcb.2014.05.002

    View details for Web of Science ID 000343630000003

    View details for PubMedID 24953741

  • LC3 Binding to the Scaffolding Protein JIP1 Regulates Processive Dynein-Driven Transport of Autophagosomes DEVELOPMENTAL CELL Fu, M., Nirschl, J. J., Holzbaur, E. L. 2014; 29 (5): 577-590


    Autophagy is essential for maintaining cellular homeostasis in neurons, where autophagosomes undergo robust unidirectional retrograde transport along axons. We find that the motor scaffolding protein JIP1 binds directly to the autophagosome adaptor LC3 via a conserved LIR motif. This interaction is required for the initial exit of autophagosomes from the distal axon, for sustained retrograde transport along the midaxon, and for autophagosomal maturation in the proximal axon. JIP1 binds directly to the dynein activator dynactin but also binds to and activates kinesin-1 in a phosphorylation-dependent manner. Following JIP1 depletion, phosphodeficient JIP1-S421A rescues retrograde transport, while phosphomimetic JIP1-S421D aberrantly activates anterograde transport. During normal autophagosome transport, residue S421 of JIP1 may be maintained in a dephosphorylated state by autophagosome-associated MKP1 phosphatase. Moreover, binding of LC3 to JIP1 competitively disrupts JIP1-mediated activation of kinesin. Thus, dual mechanisms prevent aberrant activation of kinesin to ensure robust retrograde transport of autophagosomes along the axon.

    View details for DOI 10.1016/j.devcel.2014.04.015

    View details for Web of Science ID 000337644700010

    View details for PubMedID 24914561

    View details for PubMedCentralID PMC4109720

  • JIP1 regulates the directionality of APP axonal transport by coordinating kinesin and dynein motors JOURNAL OF CELL BIOLOGY Fu, M., Holzbaur, E. L. 2013; 202 (3): 495-508


    Regulation of the opposing kinesin and dynein motors that drive axonal transport is essential to maintain neuronal homeostasis. Here, we examine coordination of motor activity by the scaffolding protein JNK-interacting protein 1 (JIP1), which we find is required for long-range anterograde and retrograde amyloid precursor protein (APP) motility in axons. We identify novel interactions between JIP1 and kinesin heavy chain (KHC) that relieve KHC autoinhibition, activating motor function in single molecule assays. The direct binding of the dynactin subunit p150(Glued) to JIP1 competitively inhibits KHC activation in vitro and disrupts the transport of APP in neurons. Together, these experiments support a model whereby JIP1 coordinates APP transport by switching between anterograde and retrograde motile complexes. We find that mutations in the JNK-dependent phosphorylation site S421 in JIP1 alter both KHC activation in vitro and the directionality of APP transport in neurons. Thus phosphorylation of S421 of JIP1 serves as a molecular switch to regulate the direction of APP transport in neurons.

    View details for DOI 10.1083/jcb.201302078

    View details for Web of Science ID 000322769400011

    View details for PubMedID 23897889

    View details for PubMedCentralID PMC3734084

  • Retrograde axonal transport: pathways to cell death? TRENDS IN NEUROSCIENCES Perlson, E., Maday, S., Fu, M., Moughamian, A. J., Holzbaur, E. L. 2010; 33 (7): 335-344


    Active transport along the axon is crucial to the neuron. Motor-driven transport supplies the distal synapse with newly synthesized proteins and lipids, and clears damaged or misfolded proteins. Microtubule motors also drive long-distance signaling along the axon via signaling endosomes. Although positive signaling initiated by neurotrophic factors has been well-studied, recent research has focused on stress-signaling along the axon. Here, the connections between axonal transport alterations and neurodegeneration are discussed, including evidence for defective transport of vesicles, mitochondria, degradative organelles, and signaling endosomes in models of amyotrophic lateral sclerosis, Huntington's, Parkinson's and Alzheimer's disease. Defects in transport are sufficient to induce neurodegeneration, but recent progress suggests that changes in retrograde signaling pathways correlate with rapidly progressive neuronal cell death.

    View details for DOI 10.1016/j.tins.2010.03.006

    View details for Web of Science ID 000280279900005

    View details for PubMedID 20434225