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Stadtman Investigator

Ariel Levine, M.D., Ph.D.

Spinal Circuits and Plasticity Unit

Spinal Circuits and Plasticity Unit (SCPU)
Building 35 Room 2B-1002
35 Convent Drive MSC3702
Bethesda MD 20892
Office: 301-402-6935
Lab: 301-402-6935
Fax: 301-496-4276
ariel.levine@nih.gov

Dr. Levine received an undergraduate degree in biology from Brandeis University in 2000, a Ph.D. from The Rockefeller University in 2008, and an M.D. from Cornell University in 2009. During her graduate research with Dr. Ali Brivanlou, she studied the role of TGF-β signaling during embryonic development. Dr. Levine did postdoctoral research with Dr. Samuel Pfaff at The Salk Institute, where she identified a novel population of spinal neurons that encode “motor synergies” – modular neural programs for simple movements that are thought to underlie a wide variety of common behaviors. She was an Associate Member of the Reeve Foundation Consortium and a Fellow of the George Hewitt Foundation. She joined NINDS in 2015 where her lab studies how the molecules, neurons, and circuits of the spinal cord mediate normal behavior and learn.

The spinal cord is the major link between the brain and the body. It receives cues from the cortex, the brainstem, and other sources, and transforms these diverse inputs into behavior. In addition, it is the primary relay point for sensory pathways from the body and constantly integrates multiple streams of information about body position, touch, and pain. We seek to understand how the diverse cell types of the spinal cord function together to mediate normal behavior. Ultimately, we hope to use this knowledge to improve recovery for patients with stroke and spinal cord injury. We are guided by three key questions:

 

What are the cell types of the mammalian spinal cord? Using massively parallel single nucleus RNA sequencing, we established the first molecular and cellular atlas of the adult spinal cord. This work identified different organization of the dorsal and ventral regions of the spinal cord, revealed novel populations, and serves as an important reference to our field. In ongoing work, we use similar techniques to probe cell-type specific changes in different behaviors and in response to injury and disease. We also develop new computational approaches to analyze single cell spinal cord data.

 

How do specific spinal cord cell types contribute to behavior? We use mouse genetics, cell type specific manipulations, and behavioral analysis to reveal how specific neuronal populations contribute to movement and to motor learning. In addition, we are interested in the molecular basis of neuronal diversity - how the unique molecular repertoire of each neuronal population serves its cellular and circuit functions.

 

How are spinal cord cells incorporated into central nervous system-wide circuits for motor control? We study how descending pathways from different areas of the brain target specific spinal cord populations to help mediate coordinated movements.

 




Spinal neurons in the pre-motor network controlling the gastrocnemius (calf) muscle, color-coded by depth from the dorsal surface.

Staff Image
  • Fabricio do Couta Nicola, Ph.D.
    Postdoctoral Fellow

  • Li Li, M.S.
    Animal Biologist

  • Kaya Matson, B.A.
    Graduate Student
    NIH-Johns Hopkins University Graduate Partnership

  • Ryan Patterson, M.Sc
    Research Fellow

  • Anupama Sathyamurthy, Ph.D.
    Postdoctoral Fellow

  • Stefan Stoica, B.A.
    Postbaccalaureate IRTA Fellow, Research Assistant

  • Tugba Topal, Ph.D.
    Postdoctoral Fellow

  • 1) Courtney IDobrottAnupamaSathyamurthyAriel JLevine (2019)
  • Decoding cell type diversity within the spinal cord
  • Current Opinion in Physiology, 8, 1-6
  • 2) Matson KJE, Sathyamurthy A, Johnson KR, Kelly MC, Kelley MW, Levine AJ (2018)
  • Isolation of Adult Spinal Cord Nuclei for Massively Parallel Single-nucleus RNA Sequencing.
  • Journal of Visualized Experiments
  • 3) Hayashi, M; Hinckley, CA; Driscoll, SP; Moore, NJ; Levine, AJ; Hilde, KL; Sharma, K; Pfaff, SL (2018)
  • Graded arrays of spinal and supraspinal V2a interneuron subtypes underlie forelimb and hindlimb motor control
  • Neuron, 97, 869-884
  • 4) Sathyamurthy, A*; Johnson, KR*; Matson, KEJ; Li, Li; Ryba, AR; Bergman, TB; Dobrott, CI; Kelly, MC; Kelley, MW; Levine, AJ (2018)
  • Massively Parallel Single Nucleus Transcriptional Profiling Defines Spinal Cord Neurons and Their Activity During Behavior
  • Cell Reports, 22, 2216-2225
  • 5) Hilde, KL; Levine, AJ; Hinckley, CA; Hayashi, M; Montgomery, JM; Gullo, M; Driscoll, SP; Grosschedl, R; Kohwi, Y; Kohwi-Shigematsu, T; Pfaff, SL. (2016)
  • Satb2 is required for the development of a spinal exteroceptive microcircuit that modulates limb position.
  • Neuron, 91, 763-776
  • 6) Pawar, K; Cummings, B; Thomas, A; Shea, L; Levine, A; Pfaff, S; Anderson, A (2015)
  • Biomaterial bridges enable regeneration and re-entry of corticospinal tract axons into the caudal spinal cord after SCI: association with recovery of forelimb function
  • Biomaterials, 65, 1-12
  • 7) Levine, AJ*, Hinckley, CA*, Hilde, KL, Driscoll, SP, Poon, TH, Montgomery, JM, Pfaff, SL (2014)
  • Identification of a cellular node for motor control pathways
  • Nature Neuroscience, 17, 586:593. *equal contribution
  • 8) Levine, AJ; Lewallen KA; Pfaff SL (2012)
  • Spatial organization of cortical and spinal neurons controlling motor behavior
  • Current Opinions in Neurobiology, 22, 812-21
  • 9) Levine, AJ; Levine, ZJ; Brivanlou, AH (2009)
  • GDF-3 is a BMP inhibitor that can activate Nodal signaling only at very high doses
  • Developmental Biology , 325, 43-8
  • 10) Levine, AJ and Brivanlou, AH. (2008)
  • Molecular Basis of Pluripotency.
  • chapter in “Principles of Regenerative Medicine.” Ed Atala, A; Lanza, R. Academic Press, pp 118-127. ISBN 978-0-12-369410-2.
  • 11) Levine, AJ and Brivanlou, AH (2007)
  • Proposal of a Model of Mammalian Neural Induction
  • Developmental Biology, 308, 247-256
  • 12) Levine, AJ and Brivanlou, AH (2006)
  • GDF-3, a BMP inhibitor, regulates cell fate in stem cells and early embryos
  • Development, 133, 209-216
  • 13) Levine, AJ and Brivanlou, AH (2006)
  • GDF3 at the Crossroads of TGF-B Signaling
  • Cell Cycle , 5, 1069-1073
  • 14) James, D; Levine, AJ; Besser, D; Hemmati-Brivanlou, A (2005)
  • TGF-ß/activin/nodal signaling is necessary for the maintenance of pluripotency in human embryonic stem cells
  • Development , 132, 1273-1282
  • 15) Levine, AJ; Munoz-Sanjuan, I; Bell, E; North, AJ; Brivanlou, AH (2003)
  • ) Fluorescent labeling of endothelial cells allows in vivo, continuous characterization of the vascular development of Xenopus laevis
  • Developmental Biology , 254, 50-67
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