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Related Research Units

Rosamund Stone Zander Translational Neuroscience Center (RSZ TNC) Research
Neurology Research
F.M. Kirby Neurobiology Center

Research Overview

Current projects:

  1. Developing a novel inducible mouse model for gene therapy and enzyme replacement therapy (ERT) in succinic semialdehyde dehydrogenase deficiency (SSADHD)
  2. Developing a novel mouse model of PTEN deletion and testing novel pharmacotherapy for PTEN Hamartoma Tumor Syndrome (PHTS).

Research Background

Dr. Lee is a trained molecular neurobiologist interested in understanding the molecular mechanisms underlying neuronal inhibition, brain plasticity and functional recovery as it pertains to brain development and brain trauma. Dr. Lee combined molecular biology and electrophysiology techniques to discover that phosphorylation-dependent turnover of potassium chloride co-transporter KCC2 controls Cl- mediated GABAergic inhibition (Lee et al., Nat Neurosci, 2011). He also used novel genetic mouse models to dissect a paracrine signaling mechanism underlying critical period (CP) plasticity control (Spatazza, Lee et al., Cell Rep, 2013; Lee et al., Mol Psychiatry, 2017).

Dr. Lee's translational research included functional recovery after nerve damage (Bei, Lee et al., Cell, 2016) and traumatic brain injury (Hsieh, Lee et al., Cerebral Cortex, 2016). More recently, Dr. Lee focuses on a rare inborn GABA metabolic disorder SSADH deficiency. By developing a SSADHD mouse tool that allows ‘on-demand’ SSADH restoration, Dr. Lee aims to contribute to the preclinical development of novel SSADHD therapies.

Selected Publications

  1. Lee HHC, Walker JA, Williams JR, Goodier RR, Payne JA & Moss SJ (2007). Direct PKC-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter, KCC2. The Journal of Biological Chemistry 282:29777-29784. PMID:17693402.
  2. Lee HHC, Deeb TZ, Walker JA, Davies PA & Moss SJ (2011). NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor mediated currents. Nature Neuroscience 14:736-743. PMCID: PMC3102766.
  3. *Beurdeley M, *Spatazza J, *Lee HHC, Sugiyama S, Bernard C, Di Nardo AA, Hensch TK & Prochiantz A (2012). Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. Journal of Neuroscience 32:9429-9437. PMCID: PMC3419577. *co-first author
  4. *Spatazza J, *Lee HHC, Tibaldi L, Joliot A, Di Nardo AA, Hensch TK & Prochiantz A (2013). Choroid plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep 3:1815-1823. PMCID: PMC4119931. *co-first author
  5. *Bei F, *Lee HHC, Liu X, Gunner G, Jin H, Ma L, Wang C, Hensch TK, Frank E, Sanes J, Chen C, Fagiolini M & He Z (2016). Restoration of visual function by enhancing conduction in regenerated axons. Cell 164:219-232. PMCID: PMC4863988. *co-first author
  6. *Hsieh TH, *Lee HHC, Hameed MQ, Pascual-Leone A, Hensch TK & Rotenberg A (2016). Trajectory of parvalbumin cell impairment and loss of cortical inhibition in post-traumatic epileptogenesis. Cerebral Cortex 27:5509-5524. PMCID: PMC6075565. *co-first author
  7. Lee HHC, Bernard C, Ye Z, Acampora D, Simeone A, Prochiantz A, Di Nardo A & Hensch TK (2017). Genetic Otx2 mis-localization delays critical period plasticity across brain regions. Mol Psychiatry 22:680-688. PMCID: PMC5400722.
  8. MacMullin PC, Hodgson NW, Damar U, Lee HHC, Dhamne SC, Hyde D, Hameed M, Conley G, Morriss N, Qiu J, Mannix R, Hensch TK & Rotenberg A (2020). Long-term changes in excitation/inhibition balance underlies seizure susceptibility in a rodent model of repeated mild traumatic brain injury. Cerebral Cortex 30:6108-6120. PMCID: PMC8248830.
  9. **Lee HHC, Pearl PL & Rotenberg A (2021). Enzyme replacement therapy for succinic semialdehyde dehydrogenase deficiency: relevance in aminobutyric acid plasticity. J Child Neurol. 36:1200-1209. PMCID: PMC8382780. **corresponding author
  10. **Lee HHC, McGinty GE, Pearl PL & Rotenberg A (2022). Understanding the molecular mechanisms of succinic semialdehyde dehydrogenase deficiency (SSADHD): towards the development of SSADH-targeted medicine. Int J Mol Sci. 23:2606. PMCID: PMC8910003. **corresponding author

Publications

  1. Understanding the Molecular Mechanisms of Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD): Towards the Development of SSADH-Targeted Medicine. Int J Mol Sci. 2022 Feb 26; 23(5). View Abstract
  2. Enzyme Replacement Therapy for Succinic Semialdehyde Dehydrogenase Deficiency: Relevance in ?-Aminobutyric Acid Plasticity. J Child Neurol. 2021 11; 36(13-14):1200-1209. View Abstract
  3. Increase in Seizure Susceptibility After Repetitive Concussion Results from Oxidative Stress, Parvalbumin-Positive Interneuron Dysfunction and Biphasic Increases in Glutamate/GABA Ratio. Cereb Cortex. 2020 11 03; 30(12):6108-6120. View Abstract
  4. Ceftriaxone Treatment Preserves Cortical Inhibitory Interneuron Function via Transient Salvage of GLT-1 in a Rat Traumatic Brain Injury Model. Cereb Cortex. 2019 12 17; 29(11):4506-4518. View Abstract
  5. Trajectory of Parvalbumin Cell Impairment and Loss of Cortical Inhibition in Traumatic Brain Injury. Cereb Cortex. 2017 12 01; 27(12):5509-5524. View Abstract
  6. Genetic Otx2 mis-localization delays critical period plasticity across brain regions. Mol Psychiatry. 2017 05; 22(5):680-688. View Abstract
  7. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-232. View Abstract
  8. KCC2 activity is critical in limiting the onset and severity of status epilepticus. Proc Natl Acad Sci U S A. 2015 Mar 17; 112(11):3523-8. View Abstract
  9. Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep. 2013 Jun 27; 3(6):1815-23. View Abstract
  10. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci. 2012 Jul 04; 32(27):9429-37. View Abstract
  11. Hyperpolarizing GABAergic transmission depends on KCC2 function and membrane potential. Channels (Austin). 2011 Nov-Dec; 5(6):475-81. View Abstract
  12. NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor-mediated currents. Nat Neurosci. 2011 Jun; 14(6):736-43. View Abstract
  13. Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci. 2010 Oct; 45(2):173-9. View Abstract
  14. Direct protein kinase C-dependent phosphorylation regulates the cell surface stability and activity of the potassium chloride cotransporter KCC2. J Biol Chem. 2007 Oct 12; 282(41):29777-84. View Abstract
  15. Identification of the sites for CaMK-II-dependent phosphorylation of GABA(A) receptors. J Biol Chem. 2007 Jun 15; 282(24):17855-65. View Abstract
  16. Transcriptional regulation of acetylcholinesterase-associated collagen ColQ: differential expression in fast and slow twitch muscle fibers is driven by distinct promoters. J Biol Chem. 2004 Jun 25; 279(26):27098-107. View Abstract
  17. Muscle induces neuronal expression of acetylcholinesterase in neuron-muscle co-culture: transcriptional regulation mediated by cAMP-dependent signaling. J Biol Chem. 2003 Nov 14; 278(46):45435-44. View Abstract
  18. ATP induces post-synaptic gene expressions in vertebrate skeletal neuromuscular junctions. J Neurocytol. 2003 Jun-Sep; 32(5-8):603-17. View Abstract

Contact Henry Lee

Phone: 617-919-3152
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