Download BIOGRAPHICAL SKETCH NAME: Yoo, Soonmoon eRA COMMONS

OMB No. 0925-0001/0002 (Rev. 08/12 Approved Through 8/31/2015)
BIOGRAPHICAL SKETCH
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NAME: Yoo, Soonmoon
eRA COMMONS USER NAME (credential, e.g., agency login): soonmoonyoo
POSITION TITLE: Research Scientist
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing,
include postdoctoral training and residency training if applicable. Add/delete rows as necessary.)
INSTITUTION AND LOCATION
DEGREE
(if
applicable)
Completion
Date
MM/YYYY
FIELD OF STUDY
Chung-Ang University, Seoul, South Korea
Chung-Ang University, Seoul, South Korea
University of Texas Medical Branch, Galveston, TX
B.S.
M.S.
Ph.D.
02/1994
08/1996
05/2003
Biology
Biochemistry
Physiology & Biophysics
Georgetown University, Washington, DC
Nemours Biomedical Research, Wilmington, DE
Postdoctoral
Postdoctoral
12/2006
08/2010
Neuroscience
Neurobiology
A. Personal Statement
The long-term goal of this proposed study is: (1) to identify and characterize neuronal piRNAs in axons of
sciatic nerve, (2) to profile and contrast levels of piRNAs in axonal vs. cell body compartment s at different
times after injury, (3) to identify PIWI/piRNA-target genes that are transported into distal axons, and (4)
examine roles of the axonal piRNAs in regenerating axons. I, a New Investigator, have worked in the field of
neural regeneration for more than a decade, using in vivo and in vitro models including invertebrate giant
axons, primary mammalian neurons in culture and rodent spinal cord and sciatic nerve injury, and have
focused on the cellular and molecular mechanisms underlying spontaneous resealing of injured axoplasmic
membrane followed by regeneration. Using adult rat peripheral injury model, we have successfully developed
live cell imaging and local translation monitoring methodologies (FRAP), the qualitative and quantitative
fluorescence in situ hybridization (FISH) protocols and subcellular compartment isolation technique that are
necessary for studies of the axonal mRNA and miRNA localization and local protein synthesis. My laboratory is
recently well-versed in a RNA-immunoprecipitation (RIP) technique and RNA-electrophoresis mobility shift
assay (REMSA) to identify the cognate mRNA population. We have very recently started investigating
mechanisms of mature and precursor miRNAs that are localized into axonal compartments of neurons,
supported by R21 funding. The studies proposed here are built on the very exciting findings from these
profiling studies using Next Generation Deep Sequencing. Although it took some time for me to start
publishing my independent work from my own group, I think that we are finally producing very exciting data that
the neuroscience as well as cellular/molecular biology community will accept. The studies proposed here will
combine several methodologies that we have been successfully optimized and utilized in collaboration (NGS,
axoplasm purification, FISH, CLIP and microfluidic device), and directly apply these systems and the unique
reagents for study regulatory mechanisms of intra-axonal protein synthesis to improve regeneration in nerve
injury.
1. Yudin, D., Hanz, S., Yoo, S., Iavnilovitch, E., Willis, D., Gradus, T., Vuppalanchi, D., Segal-Ruder, Y., BenYaakov, K., Hieda, M., Yoneda, Y., Twiss, J.L. & Fainzilber, M. (2008). Localized regulation of axonal
RanGTPase controls retrograde injury signaling in peripheral nerve. Neuron 59(2): 241-52. PMCID:
PMC2538677.
2. Yoo, S., Kim, H.H., Donnelly, C.J., Vuppalanchi, D., Kim, P., Park, M., Lee, S.J., Merianda, T.T., PerroneBizzozero, N., Twiss, J.L. (2013). A HuD-ZBP1 ribonucleoprotein complex localizes GAP-43 mRNA into
axons through its 3’ untranslated region AU-rich regulatory elements. J Neurochem. 126: 792-804. PMCID:
PMC3766383.
3. Kim, H.H., Kim, P., Phay, M. & Yoo, S. (2015). Identification of precursor microRNAs within distal axons of
sensory neuron. J. Neurochem. 134:193-9. PMCID: PMC4490939.
4. Kim, H.H., Lee, S.J., Gardiner, A.S., Perrone-Bizzozero, N.I. & Yoo, S. (2015). Different motif requirements
for the localization zipcode element of β-actin mRNA binding by HuD and ZBP1. Nucleic Acid Res.
43:7432-46. PMCID: PMC4551932.
B. Positions and Honors
Positions and Employment
1994-1996
Teaching Assistant, Department of Biochemistry, School of Graduate Studies, Chung-Ang
University, Seoul, South Korea
1997-2002
Graduate Assistant, Department of Physiology and Biophysics, University of Texas Medical
Branch, Galveston, TX
2003-2006
Postdoctoral fellow (with Dr. Jean R. Wrathall), Department of Neuroscience, Georgetown
University Medical Center, Washington, DC
2006-2010
Postdoctoral fellow (with Dr. Jeffery L. Twiss), Nemours Biomedical Research, Alfred I duPont
Hospital for Children, Wilmington, DE
2010-2013
Assistant Research Scientist, Human Genetics Research Laboratory, Nemours Biomedical
Research, Alfred I duPont Hospital for Children, Wilmington, DE
2012Affiliated Scientist, Department of Biological Sciences, University of Delaware, Newark, DE
2012-2013
Guest Lecturer, Department of Biology, Drexel University, Philadelphia, PA
2013Research Scientist, Molecular Regeneration and Neuroimaging Laboratory, Nemours
Biomedical Research, Alfred I duPont Hospital for Children, Wilmington, DE
2014Research Assistant Professor, Department of Pediatrics, Thomas Jefferson University Medical
College, Philadelphia, PA
Other Experience and Professional Memberships
1998Member, Society for Neuroscience
2005-2007
Member, International Society for Neurochemistry
2010-2013
Member, American Society for Cell Biology
2005Journal of Neurochemistry, ad hoc reviewer
2007Developmental Neurobiology, ad hoc reviewer
2008Journal of Neuroscience, ad hoc reviewer
2010EMBO Journal, ad hoc reviewer
2011Journal of Cell Science, ad hoc reviewer
2012Molecular & Cellular Proteomics, ad hoc reviewer
2014Editorial Board, The Journal of DNA and RNA Research, Open Access Pub
2014Cellular and Molecular Neurobiology, ad hoc reviewer
Honors
2003
George Sealy Research Award in Neurology, The University of Texas Medical Branch,
Galveston, Texas, USA
C. Contribution to Science
1. My early interests in neurobiology/neuroscience focused on the cellular mechanisms underlying neural
repair of both invertebrate and mammalian axons following mechanical injury. I demonstrated for the first
time that the injury distance from the cell body is the main determinant of cell fate after injury via
extracelluar calcium ions influxed and accumulated into cell body. This finding brought us to new frontiers
in understanding the fundamental mechanisms for axolemmal repair after neuronal injury and multiple roles
of calcium ion in neurons. I also enabled to show that axolemmal repair after injury requires some synaptic
vesicle fusion proteins, such as syntaxin and synaptotagmin. These works were published in several peer-
reviewed journals, in which I served as the primary or co-investigator.
a. Yoo, S., Bottenstein, J.E., Bittner, G.D., and Fishman, H.M. 2004. Survival of Mammalian B104 Cells
following Neurite Transection at Different Locations Depends on Somal Ca2+ Concentration. J.
Neurobiol. 60:137-153. PMID: 15266646.
b. Yoo, S., Nguyen, M.P., Fukuda, M., Bittner, G.D., Fishman, H.M. 2003. Plasmalemmal Sealing of
Transected Mammalian Neurites is a Gradual Process Mediated by Ca2+-regulated Proteins. J.
Neurosci. Res. 74:541-551. PMID: 14598298.
c. Detrait, E.R., Eddleman, C.S., Yoo, S., Fukuda, M., Nguyen, M.P., Bittner, G.D., Fishman, H.M. 2000.
Axonal repair requires proteins that mediate synaptic vesicle fusion. J. Neurobiol. 44:382-391. PMID:
10945894.
d. Detrait, E.R., Yoo, S., Eddleman, C.S., Fukuda, M., Bittner, G.D., Fishman, H.M. 2000. Plasmalemmal
repair of severed neurites of PC12 cells requires Ca2+ and synaptotamin. J. Neurosci. Res. 62: 566573. PMID: 11070500.
2. I further expanded my research agenda and explored nerve regeneration using an animal model of spinal
cord injury (SCI). I was one of the first to demonstrate that SCI stimulates the proliferation of NG2+ cells
with the properties of oligodendrocytes progenitor cells (OPCs) in adult rodents [13]. The method that I
developed to purify OPCs from adult spinal cord enabled us to characterize the properties of precursor
cells in the adult CNS and evaluate the therapeutic potential to improve recovery after SCI. My research
has further shown that activated microglia and macrophages, the predominant cell types at the site of SCI,
produce factors that inhibit oligodendrogenesis in vivo after SCI [14]. These studies clearly suggest that
activated microglia/macrophages and factors secreted by them could contribute to an inhibitory
microenvironment in the SCI lesion per se, interfering with the proliferation and differentiation of
endogenous NG2+ OPCs and preventing functional recovery in SCI patients.
a. Wu, X.F., Yoo, S., Wrathall, J.R. 2005. Real-time PCR analysis of temporal-spatial alterations in gene
expression after spinal cord contusion. J. Neurochem. 93:943-952. PMID: 15857397.
b. Zai, L.J., Yoo, S., Wrathall, J.R. 2005. Increased growth factor expression and cell proliferation after
contusive spinal cord injury. Brain Res. 1052:147-155. PMID: 19005441.
c. Yoo, S., Wrathall, J.R. 2007. Mixed primary culture and clonal analysis provide evidence that NG2
proteoglycan-expressing cells after spinal cord injury are glial progenitors. Dev. Neurobiol. 67:860-874.
PMID: 17506499.
d. * Wu, J., * Yoo, S., Wilcock. D., Lytle, J.M., Leung, P.Y., Colton, C.A., Wrathall, J.R. 2010. Interaction of
NG2+ glial progenitors and microglia/macrophages from the injured spinal cord. Glia. 58:410-422.
PMCID: PMC2807472 (* J. Wu and S. Yoo contributed equally to this work).
3. Neurons in CNS have little capacity for regeneration but PNS neurons show significant morphologic/
functional recovery after injury. However, it is still unclear what causes the differences between these
neurons and how this must be solved for successful regeneration of CNS nerve. By focusing on molecular
mechanisms that regulate RNA axonal localization and de novo protein synthesis in distal axons needed to
regenerate axons of PNS neurons, I have devoted substantial effort to develop robust methods to dissect
the roles of cis-elements within mRNA for localization and axonal translational control using live cell
imaging approaches and quantification methods (qFISH). Although this is still an underexplored topic, I
directly demonstrated that specific RNAs encoding proteins that trigger injury-induced responses in the cell
body contain the localization cis-elements within the 3’UTR, which are specifically recognized by transacting RNA-binding proteins. I also enabled to show that axonally synthesized proteins participate in
autonomous function of distal axons via spatial and temporal regulation of local protein synthesis. Very
recently, our new studies clearly demonstrated that specific small non-coding regulatory miRNAs actively
localize into distal axons and locally maturated into functional mature miRNAs to spatially regulate local
protein synthesis. Current studies are expanding the mechanistic research of axonal mRNA transport and
regulation of local protein synthesis medicated by miRNAs and/or piRNAs to in vivo biological relevance of
these axonal mRNAs in regenerating axons. On completion of these small non-coding RNA-mediated
translation regulation in distal axons, I will, for the first time, demonstrate mRNA-independent localization of
precursor miRNAs and axon-specific PIWI/piRNA complexes in distal axons. The elucidation of
cellular/molecular mechanisms of control of local protein synthesis within the axonal compartment at
different levels of neuronal activity including regenerative processes could lead to the development of RNAbased approaches for the therapy of neurological disorders.
a. Donnelly, C.J., Park, M., Spillane, M., Yoo, S., Pacheco, A., Gomes, C., Kim, H.H., Merianda, T.T.,
Gallo, G., Twiss, J.L. 2013. Axonally synthesized β-actin and GAP-43 proteins support distinct modes
of axonal growth. J. Neurosci. 33: 3311-22. PMCID: PMC3739791.
b. Yoo, S., Kim, H.H., Kim, P., Donnelly, C.J., Kalinski, A.L., Vuppalanchi, D., Park, M., Lee, S.J.,
Merianda, T.T., Perrone-Bizzozero, N.I., Twiss, J.L. 2013. A HuD-ZBP1 ribonucleoprotein complex
localizes GAP-43 mRNA into axons through its 3’ untranslated region AU-rich regulatory element. J.
Neurochem. 126: 792-804. PMCID: PMC3766383.
c. Merianda, T.T., Coleman, J., Kim, H.H., Kumar Sahoo, P., Gomes, C., Brito-Vargas, P., Rauvala, H.,
Blesch, A., Yoo, S. & Twiss, J.L. (2015). Axonal amphoterin mRNA is regulated by translational control
and enhances axon outgrowth. J Neurosci. 35(14): 5693-706. PMCID: PMC3755718
d. Phay, M., Kim, H.H., & Yoo, S. (2015). Identification of precursor microRNAs within distal axons of
sensory neuron. PLoS One 10:e0137461. PMCID: PMC4557935.
Complete List of Published Work in MyBibliography:
http://www.ncbi.nlm.nih.gov/sites/myncbi/1NM9zAe7iHi57/bibliography/47276267/public/?sort=date&di
rection=ascending
D. Research Support
Ongoing Research Support
P20GM103464
Shaffer (PI)
09/07/10-06/30/16
NIH/NCRR/NIGMS: Centers of Biomedical Research Excellence II (COBRE II), Center for Pediatric Research
“Temporal regulation of localized mRNA translation in regenerating axon”
The goals of this proposal are to determine the intracellular pathways that underlay the local translational control
to confer temporal specificity to local mRNA translation after axonal injury, and to examine how the axon chooses
which mRNAs to translate in response to any given stimulus.
Role: Target Investigator
R21 NS085691
Yoo (PI)
10/01/13-09/30/16
“Profiling and characterizing axonal precursor microRNAs in regenerating nerve”
The major goals of this project are to profile changes of the precursor and mature miRNA expression levels in the
axonal compartments following sciatic nerve injury and to identify the cis-acting region(s) of precursor miRNAs
and trans-acting factor(s) that are required for localization.
Role: PI
Completed Research Support
Delaware INBRE Core Center Access Award
Yoo (PI)
09/05/14-03/05/15
Delaware INBRE
“Profiling mature microRNAs and piRNAs in regenerating peripheral nerve”
The goal of this award is to determine if neuron-specific small non-coding RNAs including miRNAs and piRNAs
reveal differential expression in response to injury during regeneration.
Role: PI
Post-doctoral Fellowship Award 124124
Yoo (PI)
07/01/2009 – 09/17/2010
Craig H. Neilsen Foundation
“Temporal regulation of localized mRNA translation in regenerating axons”
The objective of this grant is to determine how the axonal protein synthesis machinery is regulated to confer
temporal specificity to local mRNA translation after axonal injury.
Role: P.I.
2 P20 RR016472-11
Steiner (PI)
03/01/2012 – 02/28/2014
Delaware INBRE
“Defining the role of Sonic hedgehog mediated regulation of Na,K-ATPase in medulloblastoma”
A collaboration with Dr. Sigrid A. Langhans (a PI of the pilot grant), Yoo is helping for isolating primary granule
cells from mouse medulloblastoma and providing with constructs to generate the dual reporter or Dendra2
photoconvertible systems for analyzing intracellular trafficking pathways in neurons using confocal live cell
imaging.
Individual Research Grants WB2-0403-2
Wrathall (PI)
01/01/2005 - 12/31/2006
Christopher Reeve Paralysis Foundation
“Endogenous Precursor Cells in Chronic SCI”
This project will test the hypothesis that chronically after contusion injury there remain a larger than normal
population of glial precursors cells that can be stimulated to divide and differentiate to improve function after
SCI.
Role: Co-Investigator