Haesun Kim

Haesun Kim

Email

haekim [at] newark.rutgers.edu

Phone

973-353-1454,973-353-1455

Office Location

501C Life Sciences Center

 Research Projects

One of the goals of my research program to define the mechanisms that underlie myelin abnormalities in the PNS.  Using both cellular and animal models for peripheral neuropathies, we focus on understanding the genetic and intracellular signaling mechanisms that modulate Schwann cell myelination and myelin maintenance.  Ultimately, we will use this information to design therapies to promote PNS recovery and function in diseases such as Charcot-Marie-Tooth (CMT) diseases, diabetic neuropathy and nerve trauma by promoting myelin repair and preventing myelin loss.  We are also interested in elucidating the molecular mechanisms underlying myelin abnormalities associated with mild traumatic brain injury.  Our extensive work on Schwann cells demonstrated an essential role for the external regulators such as growth factors and cell adhesion molecules in Schwann cell differentiation and myelination.  We also demonstrated the importance of MAPK kinases in promoting Schwann cell plasticity, de-differentiation and myelin breakdown following PNS injury.  We have considerable expertise in using both in vitro and in vivo genetic mouse models to study Schwann cell myelination. 

1. Stemness of Schwann cell: Repair in the peripheral nervous system (PNS) depends upon the plasticity of the myelinating cells, Schwann cells, and their ability to dedifferentiate, direct axonal regrowth, re-myelinate and allow functional recovery. The ability of such an exquisitely specialized myelinating cell to revert to an immature de-differentiated cell that can direct repair is remarkable, making Schwann cells one of the very few regenerative cell types in our bodies.  We are currently investigating the role of MiTF/TFE transcription factors in promoting repair Schwann cell formation.  For the project, we use both in vitro and in vivo modes of peripheral nerve injury models combined biochemical and genetic analyses.  

2. Choline metabolism in regulation PNS myelination and repair: Cells have a limited capacity to synthesize choline, thus cells depend on protein transporters to import choline.  Choline is used to generate phospholipids, which are important components of myelin membrane.  Choline is also metabolized to synthesize phosphotidylinositols which are important signaling lipids that regulate myelin formation.  We have identified Choline-like-transporter 1 (CTL1) as a choline transporter in Schwann cells and generated Schwann cell-specific CTL1 knock-out mice.  Using the in vivo tool, we are currently investigating the role of CTL1 and choline metabolism in regulating Schwann cell myelin formation and repair. 

3. Charcot-Marie-Tooth (CMT) disease: CMT is the most common inherited demyelinating disorder affecting the peripheral nervous system (PNS).   CMT1A  is caused by mutations on PMP22 that results in the protein accumulation in the ER.  This triggers ER stress response which is believed to me one of the mechanisms that impair PNS myelin in CMT1A patients.   MiTF/TFE transcription factors master regulators of lysosomal biogenesis and autophagy, a cellular function that removes unwanted proteins (cellular clearance).  We are currently investigating the role of MiTF/TFE proteins in CMT1A-related disease mechanisms in Schwann cells and myelin abnormalities.  

4. Traumatic Brain Injury (TBI): Chronic white matter atrophy or degeneration of myelinated axons is a common occurrence after repeated concussive injury, or mild TBI, which contributes to long-term functional deficits in the patients.  This project focuses on elucidating the molecular mechanisms that contribute to myelin loss associated with mTBI.  We are currently testing the hypothesis that mechanical injury disrupts normal axon-to-oligodendrocyte signaling necessary for maintaining myelin homeostasis in the brain.  We use both in vitro myelinated axon stretch injury model and in vivo rodent mTBI models to elucidate the signaling mechanism associated with the myelin loss.  

Courses Taught

    21:120:355 Cell Biology
    26:120:524 Cell, Molecular and Developmental Biology
    26:120:526 Topics in Cell Biology: Signal Transduction

Education

B.S. in Horticulture, Seoul National University, 1988.
M.S. in Biology, University of Toledo, 1990.
Ph.D. in Cell Biology, Neurobiology and Anatomy, University of Cincinnati, 1996.
Post-doc, Dana-Farber Cancer Institute, Harvard Medical School, 1997-2003.

Publications

  1.  Adams A.A., T.L. Wood and H.A. Kim Mature and myelinating oligodendrocytes are specifically vulnerable to mild fluid percussion injury in mice. Neurotrauma Rep 2023 4(1):433-446
  2.  Adams AA, Li Y, Kim H.A., Pfister BJ. Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretch in vitro. Front Cell Neurosci. 2023 Mar 29;17:1111403. doi: 10.3389/fncel.2023.1111403. PMID: 37066078; PMCID: PMC10090399.
  3.  Kim J., A.A. Adams, P. Gokina, B. Zambrano, J. Jayakumaran, R. Dobrowolski, P. Maurel, B.J. Pfister and H.A. Kim. Mechanical stretch induces myelin protein loss in oligodendrocytes by activating Erk1/2 in a calcium dependent manner. Glia 68:2070-2085, 2020
  4.  Kim J., A. Elias, T. Lee, P. Maurel, and H.A. Kim. Tissue inhibitor of metalloproteinase-3 (TIMP-3) promotes Schwann cell myelination. ASN Neuro 9:1-12, 2017.
  5.  Basak S, D.J. Desai, E.H. Rho, R. Ramos, P. Maurel, and H.A. Kim. E-cadherin enhances neuregulin signaling and promotes Schwann cell myelination. Glia 63:1522-536, 2015.
  6.  Kim H.A., T. Mindos and D.B. Parkinson. Plastic fantastic: Schwann cells and repair of the peripheral nervous system. Stem Cells Translational Medicine  2:553-557, 2013.
  7.  Yang D.P., J. Kim, N. Syed, Y. Tung, A. Bhaskaran, T. Mindos, R. Mirsky, K.R. Jessen, P. Maurel, D.B. Parkinson, and H.A. Kim. p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination. Journal of Neuroscience 32:7158-7168, 2012.
  8.  Chen Y., H. Wang, S.O. Yoon, M.O. Hottiger, J. Svaren, K.A. Nave, and H.A. Kim, E.N. Olson and Q.R. Lu. HDAC-mediated deacetylation of NF-kB is critical for Schwann cell myelination. Nature Neuroscience 14:437-441, 2011.
  9.  Syed N., and H.A. Kim. Soluble neuregulin and Schwann cell myelination: A therapeutic potential for improving remyelination of adult axons. Molecular and Cellular Pharmacology 2:161-167, 2010.
  10.  Syed N., K. Reddy, D.P. Yang, C. Taveggia, J.L. Salzer, P. Maurel, and H.A. Kim. Soluble neuregulin-1 has bi-functional, concentration-dependent effects on Schwann cell myelination. Journal of Neuroscience 30:6122-6131, 2010.
  11.  Monnerie H., M.D. Tang-Schomer, A. Iwata, D.H. Smith, H.A. Kim and P.D. Le Roux. Dendritic alterations after dynamic axonal stretch injuy in vitro. Experimental Neurology  224:415-423, 2010.
  12.  Tyler W.A., N. Gangoli, P. Gokina, H.A. Kim, M. Covey, S. Levison and T.L. Wood. Differentiation of oligodendrocytes requires activation of mammalian target of rapamycin signaling. Journal of Neuroscience 29:6367-6378, 2009.
  13.  Crawford A., D. Desai, P. Gokina and H.A. Kim. E-cadherin expression in postnatal Schwann cell is induced by activation of cAMP-dependent protein kinase A pathway. Glia 56:1637-1647, 2008.
  14.  Yang D.P., D.P. Zhang, K.S. Mak, D.E.Bonder, S.L. Pomeroy and H.A. Kim. Schwann cell proliferation during Wallerian degeneration is not necessary for regeneration and remyelination of the peripheral nerves: axon-dependent removal of newly generated Schwann cells by apoptosis. Molecular and Cellular Neuroscience 38:80-88, 2008.