Information

Related Research Units

Rosamund Stone Zander and Hansjoerg Wyss Translational Neuroscience Center
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. Institutional Variation in Fentanyl Use for Children on Extracorporeal Membrane Oxygenation. Hosp Pediatr. 2026 Jan 01; 16(1):56-65. View Abstract
  2. Misinformation and disinformation undermine progress in pediatric research: challenges and solutions. Pediatr Res. 2025 Nov; 98(5):1600-1605. View Abstract
  3. Meconium-related obstruction: Contemporary experience in a multi-institutional consortium. J Pediatr Surg. 2026 Jan; 61(1):162545. View Abstract
  4. Improving Commitment to Family-Centered Care in the NICU: A Multicenter Collaborative Quality Improvement Project. J Perinatol. 2025 Nov; 45(11):1627-1635. View Abstract
  5. Remote versus in-person pre-service neonatal resuscitation training: A noninferiority randomized controlled trial in Ethiopia. Resuscitation. 2025 Apr; 209:110556. View Abstract
  6. The Cost of Opioid Use in High-Risk Hospitalized Infants. J Surg Res. 2024 Oct; 302:825-835. View Abstract
  7. Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US. JAMA Netw Open. 2024 03 04; 7(3):e240555. View Abstract
  8. Consensus guidelines for the diagnosis and management of succinic semialdehyde dehydrogenase deficiency. Mol Genet Metab. 2024 May; 142(1):108363. View Abstract
  9. Laryngeal mask use during neonatal resuscitation at birth: A United States-based survey of neonatal resuscitation program providers and instructors. Resusc Plus. 2024 Mar; 17:100515. View Abstract
  10. Current Trends in Invasive Closure of Patent Ductus Arteriosus in Very Low Birth Weight Infants in United States Children's Hospitals, 2016-2021. J Pediatr. 2023 12; 263:113712. View Abstract
  11. Pulmonary Hypertension in Preterm Infants Treated With Laser vs Anti-Vascular Endothelial Growth Factor Therapy for Retinopathy of Prematurity. JAMA Ophthalmol. 2022 11 01; 140(11):1085-1094. View Abstract
  12. Guidance for Cardiopulmonary Resuscitation of Children With Suspected or Confirmed COVID-19. Pediatrics. 2022 09 01; 150(3). View Abstract
  13. Active Treatment of Infants Born at 22-25 Weeks of Gestation in California, 2011-2018. J Pediatr. 2022 10; 249:67-74. View Abstract
  14. Addressing bias and knowledge gaps regarding race and ethnicity in neonatology manuscript review. J Perinatol. 2022 11; 42(11):1546-1549. View Abstract
  15. Quality improvement for neonatal resuscitation and delivery room care. Semin Perinatol. 2022 10; 46(6):151629. View Abstract
  16. Quality Improvement for Neonatal Resuscitation and Delivery Room Care. Semin Spine Surg. 2022 May 08; 100961. View Abstract
  17. 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
  18. 2022 Interim Guidance to Health Care Providers for Basic and Advanced Cardiac Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association in Collaboration With the American Academy of Pediatrics, American Association for Respiratory Care, the Society of Critical Care Anesthesiologists, and American Society of Anesthesiologists. Circ Cardiovasc Qual Outcomes. 2022 04; 15(4):e008900. View Abstract
  19. 2021 Interim Guidance to Health Care Providers for Basic and Advanced Cardiac Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19. Circ Cardiovasc Qual Outcomes. 2021 10; 14(10):e008396. View Abstract
  20. Randomized controlled trial of the "WISER" intervention to reduce healthcare worker burnout. J Perinatol. 2021 09; 41(9):2225-2234. View Abstract
  21. Prioritization framework for improving the value of care for very low birth weight and very preterm infants. J Perinatol. 2021 10; 41(10):2463-2473. View Abstract
  22. 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
  23. Cost of clinician-driven tests and treatments in very low birth weight and/or very preterm infants. J Perinatol. 2021 02; 41(2):295-304. View Abstract
  24. Population Improvement Bias Observed in Estimates of the Impact of Antenatal Steroids to Outcomes in Preterm Birth. J Pediatr. 2021 05; 232:17-22.e2. View Abstract
  25. 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
  26. Towards personalized medicine in maternal and child health: integrating biologic and social determinants. Pediatr Res. 2021 01; 89(2):252-258. View Abstract
  27. Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association. Circulation. 2020 06 23; 141(25):e933-e943. View Abstract
  28. Tracheal suctioning of meconium at birth for non-vigorous infants: a systematic review and meta-analysis. Resuscitation. 2020 04; 149:117-126. View Abstract
  29. 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
  30. Racial and Ethnic Disparities in Human Milk Intake at Neonatal Intensive Care Unit Discharge among Very Low Birth Weight Infants in California. J Pediatr. 2020 03; 218:49-56.e3. View Abstract
  31. Safety climate, safety climate strength, and length of stay in the NICU. BMC Health Serv Res. 2019 Oct 22; 19(1):738. View Abstract
  32. Racial Segregation and Inequality in the Neonatal Intensive Care Unit for Very Low-Birth-Weight and Very Preterm Infants. JAMA Pediatr. 2019 05 01; 173(5):455-461. View Abstract
  33. Survey of preterm neuro-centric care practices in California neonatal intensive care units. J Perinatol. 2019 02; 39(2):256-262. View Abstract
  34. Birth Hospitalization Costs and Days of Care for Mothers and Neonates in California, 2009-2011. J Pediatr. 2019 01; 204:118-125.e14. View Abstract
  35. Incidence Trends and Risk Factor Variation in Severe Intraventricular Hemorrhage across a Population Based Cohort. J Pediatr. 2018 09; 200:24-29.e3. View Abstract
  36. 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
  37. Racial/Ethnic Disparity in NICU Quality of Care Delivery. Pediatrics. 2017 Sep; 140(3). View Abstract
  38. Short-term costs of preeclampsia to the United States health care system. Am J Obstet Gynecol. 2017 09; 217(3):237-248.e16. View Abstract
  39. Teamwork in the NICU Setting and Its Association with Health Care-Associated Infections in Very Low-Birth-Weight Infants. Am J Perinatol. 2017 08; 34(10):1032-1040. View Abstract
  40. Genetic Otx2 mis-localization delays critical period plasticity across brain regions. Mol Psychiatry. 2017 05; 22(5):680-688. View Abstract
  41. Trends in the delivery route of twin pregnancies in the United States, 2006-2013. Eur J Obstet Gynecol Reprod Biol. 2016 Oct; 205:120-6. View Abstract
  42. Restoration of Visual Function by Enhancing Conduction in Regenerated Axons. Cell. 2016 Jan 14; 164(1-2):219-232. View Abstract
  43. Comparing NICU teamwork and safety climate across two commonly used survey instruments. BMJ Qual Saf. 2016 12; 25(12):954-961. View Abstract
  44. Effect of Catheter Dwell Time on Risk of Central Line-Associated Bloodstream Infection in Infants. Pediatrics. 2015 Dec; 136(6):1080-6. View Abstract
  45. 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
  46. Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep. 2013 Jun 27; 3(6):1815-23. View Abstract
  47. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci. 2012 Jul 04; 32(27):9429-37. View Abstract
  48. Hyperpolarizing GABAergic transmission depends on KCC2 function and membrane potential. Channels (Austin). 2011 Nov-Dec; 5(6):475-81. View Abstract
  49. NMDA receptor activity downregulates KCC2 resulting in depolarizing GABAA receptor-mediated currents. Nat Neurosci. 2011 Jun; 14(6):736-43. View Abstract
  50. Tyrosine phosphorylation regulates the membrane trafficking of the potassium chloride co-transporter KCC2. Mol Cell Neurosci. 2010 Oct; 45(2):173-9. View Abstract
  51. 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
  52. 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
  53. 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
  54. 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
  55. 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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