Current Environment:

Researcher | 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).

Researcher | 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

Researcher | Publications