Bio

Academic Appointments


Administrative Appointments


  • Assistant Professor, Stanford University School of Medicine (2011 - Present)

Honors & Awards


  • NIH Pathway to Independence (K99/R00), NINDS (2009-2014)
  • William and Bernice E Bumpus Foundation Innovation Award, William and Bernice E Bumpus Foundation (2011-2014)
  • Alfred P. Sloan Research Fellow 2012, Alfred P. Sloan Foundation (2012-2014)
  • Gabilan Junior Faculty Fellow, Stanford University (2012-now)
  • Michael J. Fox Foundation Grant Target Validation Spring 2013, Michael J. Fox Foundation (2013-2014)
  • Klingenstein Fellowship in Neuroscience, Klingenstein Foundation (2013-2016)

Professional Education


  • Ph.D, University of Cambridge, Genetics, Neurobiology (2007)

Research & Scholarship

Current Research and Scholarly Interests


Mitochondria move and undergo fission and fusion in all eukaryotic cells. The accurate allocation of mitochondria in neurons is particularly critical due to the significance of mitochondria for ATP supply, Ca++ homeostasis and apoptosis and the importance of these functions to the distal extremities of neurons. In addition, defective mitochondria, which can be highly deleterious to a cell because of their output of reactive oxygen species, need to be repaired by fusing with healthy mitochondria or cleared from the cell. Thus mitochondrial cell biology poses critical questions for all cells, but especially for neurons: how the cell sets up an adequate distribution of the organelle; how it sustains mitochondria in the periphery; and how mitochondria are removed after damage. The goal of my research is to understand the regulatory mechanisms controlling mitochondrial dynamics and function and the mechanisms by which even subtle perturbations of these processes may contribute to neurodegenerative disorders.

Teaching

Postdoctoral Advisees


Graduate and Fellowship Programs


Publications

Journal Articles


  • The meaning of mitochondrial movement to a neuron's life BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH Lovas, J. R., Wang, X. 2013; 1833 (1): 184-194

    Abstract

    Cells precisely regulate mitochondrial movement in order to balance energy needs and avoid cell death. Neurons are particularly susceptible to disturbance of mitochondrial motility and distribution due to their highly extended structures and specialized function. Regulation of mitochondrial motility plays a vital role in neuronal health and death. Here we review the current understanding of regulatory mechanisms that govern neuronal mitochondrial transport and probe their implication in health and disease. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology.

    View details for DOI 10.1016/j.bbamcr.2012.04.007

    View details for Web of Science ID 000313932100019

    View details for PubMedID 22548961

  • PINK1 and Parkin Target Miro for Phosphorylation and Degradation to Arrest Mitochondrial Motility CELL Wang, X., Winter, D., Ashrafi, G., Schlehe, J., Wong, Y. L., Selkoe, D., Rice, S., Steen, J., LaVoie, M. J., Schwarz, T. L. 2011; 147 (4): 893-906

    Abstract

    Cells keep their energy balance and avoid oxidative stress by regulating mitochondrial movement, distribution, and clearance. We report here that two Parkinson's disease proteins, the Ser/Thr kinase PINK1 and ubiquitin ligase Parkin, participate in this regulation by arresting mitochondrial movement. PINK1 phosphorylates Miro, a component of the primary motor/adaptor complex that anchors kinesin to the mitochondrial surface. The phosphorylation of Miro activates proteasomal degradation of Miro in a Parkin-dependent manner. Removal of Miro from the mitochondrion also detaches kinesin from its surface. By preventing mitochondrial movement, the PINK1/Parkin pathway may quarantine damaged mitochondria prior to their clearance. PINK1 has been shown to act upstream of Parkin, but the mechanism corresponding to this relationship has not been known. We propose that PINK1 phosphorylation of substrates triggers the subsequent action of Parkin and the proteasome.

    View details for DOI 10.1016/j.cell.2011.10.018

    View details for Web of Science ID 000296902300021

    View details for PubMedID 22078885

  • The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial Motility CELL Wang, X., Schwarz, T. L. 2009; 136 (1): 163-174

    Abstract

    Mitochondria are mobile organelles and cells regulate mitochondrial movement in order to meet the changing energy needs of each cellular region. Ca(2+) signaling, which halts both anterograde and retrograde mitochondrial motion, serves as one regulatory input. Anterograde mitochondrial movement is generated by kinesin-1, which interacts with the mitochondrial protein Miro through an adaptor protein, milton. We show that kinesin is present on all axonal mitochondria, including those that are stationary or moving retrograde. We also show that the EF-hand motifs of Miro mediate Ca(2+)-dependent arrest of mitochondria and elucidate the regulatory mechanism. Rather than dissociating kinesin-1 from mitochondria, Ca(2+)-binding permits Miro to interact directly with the motor domain of kinesin-1, preventing motor/microtubule interactions. Thus, kinesin-1 switches from an active state in which it is bound to Miro only via milton, to an inactive state in which direct binding to Miro prevents its interaction with microtubules. Disrupting Ca(2+)-dependent regulation diminishes neuronal resistance to excitotoxicity.

    View details for DOI 10.1016/j.cell.2008.11.046

    View details for Web of Science ID 000262318400023

    View details for PubMedID 19135897

  • IMAGING AXONAL TRANSPORT OF MITOCHONDRIA METHODS IN ENZYMOLOGY, VOL 457: MITOCHONDRIAL FUNCTION, PARTB MITOCHONDRIAL PROTEIN KINASES, PROTEIN PHOSPHATASES AND MITOCHONDRIAL DISEASES Wang, X., Schwarz, T. L. 2009; 457: 319-333

    Abstract

    Neuronal mitochondria need to be transported and distributed in axons and dendrites in order to ensure an adequate energy supply and provide sufficient Ca(2+) buffering in each portion of these highly extended cells. Errors in mitochondrial transport are implicated in neurodegenerative diseases. Here we present useful tools to analyze axonal transport of mitochondria both in vitro in cultured rat neurons and in vivo in Drosophila larval neurons. These methods enable investigators to take advantage of both systems to study the properties of mitochondrial motility under normal or pathological conditions.

    View details for DOI 10.1016/S0076-6879(09)05018-6

    View details for Web of Science ID 000266544100018

    View details for PubMedID 19426876

  • Drosophila spichthyin inhibits BMP signaling and regulates synaptic growth and axonal microtubules NATURE NEUROSCIENCE Wang, X., Shaw, R., Tsang, H. T., Reid, E., O'Kane, C. J. 2007; 10 (2): 177-185

    Abstract

    To understand the functions of NIPA1, mutated in the neurodegenerative disease hereditary spastic paraplegia, and of ichthyin, mutated in autosomal recessive congenital ichthyosis, we have studied their Drosophila melanogaster ortholog, spichthyin (Spict). Spict is found on early endosomes. Loss of Spict leads to upregulation of bone morphogenetic protein (BMP) signaling and expansion of the neuromuscular junction. BMP signaling is also necessary for a normal microtubule cytoskeleton and axonal transport; analysis of loss- and gain-of-function phenotypes indicate that Spict may antagonize this function of BMP signaling. Spict interacts with BMP receptors and promotes their internalization from the plasma membrane, implying that it inhibits BMP signaling by regulating BMP receptor traffic. This is the first demonstration of a role for a hereditary spastic paraplegia protein or ichthyin family member in a specific signaling pathway, and implies disease mechanisms for hereditary spastic paraplegia that involve dependence of the microtubule cytoskeleton on BMP signaling.

    View details for DOI 10.1038/nn1841

    View details for Web of Science ID 000244175200012

    View details for PubMedID 17220882

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