Burke Medical Research Institute

785 Mamaroneck Avenue

White Plains, NY 10605

(914) 597-2551

www.burke.org

For more information contact: dwhite@burke.org

THE BURKE MEDICAL RESEARCH INSTITUTE IS AN ACADEMIC

AFFILIATE OF WEILL CORNELL MEDICINE

Special Seminar

Friday, 04/22/2016, 12:00pm - Kelsey Library

SPINAL CORD INJURY – (Axon regrowth studies in a rodent spinal cord injury model)

Do-Hun Lee, Ph.D.

Postdoctoral Associate

The Miami Project to Cure Paralysis

University of Miami Miller School of Medicine

Research abstract:

Neurons of the Central Nervous System (CNS) do not regenerate axons after injury due to intrinsic

growth limitations and inhibitory molecules in the environment. SCI studies require a variety of

experimental techniques such as animal surgery, tissue engineering, and microscopy, which I have

used to great effect in order to study these limiting factors and to promote functional recovery after

SCI. I have shown that phosphatase and tensin homolog (PTEN) deletion and chondroitinase ABC

(chABC) treatment are sufficient to increase corticospinal tract axon sprouting after a pyramidotomy

injury model (Lee et al., J. Neurosci 2014). More recently, I showed how resident NG2 cells, a major

component of the glial scar, differentiate and proliferate following SCI (Hackett and Lee et al.,

Neurobiol Dis. 2016). I have also had great success in developing a technique to trace the 3D

projections of regenerating axons using light sheet fluorescence microscopy (LSFM). I was the first to

successfully use AAV viruses to trace the regeneration of specific tracts of axons (Soderblom and Lee

et al., eNEURO 2015). My research has focused on understanding what happens after CNS injury,

protecting the spinal cord from damage, and promoting axon growth to allow maximum potential for

functional recovery. Future studies will enhance our understanding of precise signaling cascades after

CNS injury and will manipulate these cascades to produce novel strategies to treat SCI.

Recent Publications:

Hackett A, Lee DH*, Dawood A, Rodriguez M, Funk L,

Tsoulfas P, and Lee JK. STAT3 and SOCS3 regulate NG2

cell proliferation and differentiation after contusive spinal cord injury. Neurobiol Dis. 2016 May;89:10-22. (*: equal

contributor).

http://www.ncbi.nlm.nih.gov/pubmed/26804026

Soderblom C*, Lee DH*, Dawood A, Carballosa M, Santamaria AJ, Benavides FD, Jergova S, Grumbles RM,

Thomas CK, Park KK, Guest JD, Lemmon VP, Lee JK, Tsoulfas P. 3D Imaging of Axons in Transparent Spinal

Cords from Rodents and Nonhuman Primates. eNeuro

2015 Mar; 2(2) (*: equal contributor). http://www.ncbi.nlm.nih.gov/pubmed/26023683

Lee DH, Luo X, Yungher BJ, Bray E, Lee JK, Park KK. Mammalian target of rapamycin's distinct roles and

effectiveness in promoting compensatory axonal sprouting

in the injured CNS. J Neurosci. 2014 Nov 12;34(46):15347-55.

http://www.ncbi.nlm.nih.gov/pubmed/25392502

Do-HunLeePhDTheMiamiProjecttoCureParalysis

UniversityofMiamiMillerschoolofMedicine

Axonregrowthstudiesinmousespinalcordinjurymodel

SPINALCORDINJURY

SPINAL CORD INJURY Axon regrowth studies in a mouse spinal cord injury model

Do-Hun Lee, Ph.D.

NeuronsoftheCentralNervousSystem(CNS)donotregenerateaxonsafterinjuryduetointrinsicgrowthlimitationsandinhibitorymoleculesintheenvironment.SCIstudiesrequireavarietyofexperimentaltechniquessuchasanimalsurgery,tissueengineering,andmicroscopy,whichIhaveusedtogreateffectinordertostudytheselimitingfactorsandtopromotefunctionalrecoveryafterSCI.Ihaveshownthatphosphataseandtensinhomolog(PTEN)deletionandchondroitinaseABC(chABC)treatmentaresufficienttoincreasecorticospinaltractaxonsproutingafterapyramidotomyinjurymodel(Leeetal.,J.Neurosci2014).Morerecently,IshowedhowresidentNG2cells,amajorcomponentoftheglialscar,differentiateandproliferatefollowingSCI(HackettandLeeetal.,NeurobiolDis.2016).Ihavealsohadgreatsuccessindevelopingatechniquetotracethe3Dprojectionsofregeneratingaxonsusinglightsheetfluorescencemicroscopy(LSFM).IwasthefirsttosuccessfullyuseAAVvirusestotracetheregenerationofspecifictractsofaxons(SoderblomandLeeetal.,eNEURO2015).MyresearchhasfocusedonunderstandingwhathappensafterCNSinjury,protectingthespinalcordfromdamage,andpromotingaxongrowthtoallowmaximumpotentialforfunctionalrecovery.FuturestudieswillenhanceourunderstandingofprecisesignalingcascadesafterCNSinjuryandwillmanipulatethesecascadestoproducenovelstrategiestotreatSCI.