Lee Tih Shih

Associate Professor


Contact: 65167461

His research interests are in genomic and molecular investigations of human neuropsychiatric disorders, specifically human temporal lobe epilepsy, schizophrenia and longitudinal transcriptomics of Alzheimer's disease. He has a separate research program on Brain-Computer Interface (BCI) technologies with co-investigators at I2R (ASTAR) focusing on cognitive interventions for neuropsychiatric conditions e.g. Attention-Deficit Hyperactivity Disorder in children and memory loss in the elderly.

In addition to his academic and research roles in Duke University Medical School/Duke-NUS Graduate Medical School, he is also a Senior Consultant in Singapore General Hospital. His areas of specific clinical interests are in complex brain disorders, e.g. neuropsychiatric autoimmune disorders, functional neuropsychiatric disorders and atypical types of dementia.

  1. Lee T, Eid T, Mane S, Kim J, Spencer D, Ottersen O, de Lanerolle N. Aquaporin-4 is increased in the sclerotic hippocampus in human temporal lobe epilepsy. Acta Neuropathol. 2004  Dec;108(6):493-502
  2. Eid T, Lee T (joint first authors), Thomas MJ, Amiry-Moghaddam M, Bjornsen LP, Spencer DD, Agre P, Ottersen OP, de Lanerolle NC. Loss of perivascular aquaporin 4 may underlie deficient water and K+ homeostasis in the human epileptogenic hippocampus. Proc Natl Acad Sci USA 2005 Jan 25;102(4):1193-8.
  3. De Lanerolle, N, Lee, T. New Facets of the Neuropathology and Molecular Profile of Human Temporal Lobe Epilepsy, Epilepsy and Behavior, 2005, Sep: 2: 190-203.
  4. Lee, T, Bjornsen, L, Paz, C, Kim, J, Spencer, S, Spencer, D, Eid, T, de Lanerolle, N.GAT1 and GAT3 expression are difffently localized in the human epileptogenic hippocampus. Acta Neuropathol. 2006 Feb 3;1-13
  5. Eid T, Hammer J, Runden-Pran E, Roberg B, Thomas MJ, Osen K, Davanger S, Laake P, Torgner IA, Lee TS, Kim JH, Spencer DD, Ottersen OP, de Lanerolle NC. Increased expression of phosphate-activated glutaminase in hippocampal neurons in human mesial temporal lobe epilepsy. Acta Neuropathol. 2007 Feb;113(2):137-52.
  6. Lee T, Mane S, Tore E, Zhao H, Lin A, Schweitzer J, King-Stephens D, Weber P, Spencer S, Spencer D, de Lanerolle N. Gene Expression in Human Temporal Lobe Epilepsy is consistent with Increased Release of Glutamate by Astrocytes. Mol Med. 2007 Jan-Feb. 13(1-2)1-13.
  7. Lee T, Ng BY, Lee WL. Neuropsychiatry: An Emerging Field. Ann Acad Med Singapore. 2008 Jul;37(7):601-5.
  8. Tore E,  Ghosh A, Wang Y, Henning B,  Hitten P. Zaveri, Lee T, Lai J, Malthankar-Phatak G, de Lanerolle N. Recurrent seizures and brain pathology after inhibition of glutamine synthetase in the hippocampus in rats. Brain. 2008 Aug;131(Pt 8):2061-70.
  9. Eid T, Williamson A, Lee T, Petroff O, de Lanerolle N. Glutamate and Astrocytes – Key Players in Human Mesial Temporal Lobe Epilepsy. Epilepsia. 2008;49 Suppl 2:42-52.
  10. Lee T, Poon S, Chang P. Dissimilar neuropsychiatric presentations of two siblings with Juvenile Neuronal Ceroid-Lupofuscinosis. J Neuropsychiatry Clin Neurosci. 2010 Winter 22: 123.
  11. Lee T. Psychiatric manifestations in Churg-Strauss Syndrome. J Neuropsychiatry Clin Neurosci. 2009 Spring; 21(2):231-2.
  12. Lim CG, Lee T, Guan C, Fung D, Cheung YB, Teng SSW, Zhang H, Krishnan KR. Effectiveness of a Brain-Computer Interface Based Programme for Treating ADHD: A Pilot Study. Neuropsychopharmacology 2009, 36, S75–S197.
  13. Lee T, Chua S, Ly D, Song W. Genomic and Molecular characterization of Alzheimer Disease. Curr Psych Reviews. 2010 May 6(2):104-113
  14. Lee T, Krishnan R. Psychogenomics and psychiatric practice, a new paradigm. CurrPsych Reviews 2010 May 6(2):71-73
  15. Lee T, Krishnan R. Alzheimer’s Disease – An inexorable epidemic. Ann Acad Med Singapore. Ann Acad Med Singapore. 2010 Jul;39(7):505-2
  16. Lim, CG, Lee TS, Guan C, Sheng Fung DS, Cheung YB, Teng SS, Zhang H, Krishnan KR Effectiveness of a Brain-Computer Interface Based Programme for the Treatment of ADHD: A Pilot Study. Psychopharmacol Bull. 2010;43(1):73-82
  17. Kang S, Lee J, Mythily S, Liu JJ, Zhang X, Lee T, Chong S. An Integrated Genetic and Genomic Approach in the Singapore Translational and Clinical Reseach in Psychosis (STCRP): An Overview. Early Interv Psychiatry. 2011 May;5(2):91-9.
  18. Lee T. Neuropsychiatric aspects of H1N1 encephalitis. J Neuropsychiatry Clin Neurosci. 2011, Spring:23(2):E7-8
  19. Lee T, Teng S, Zhang H, Zhao Y, Lim CG, Guan CT, Fung D, Cheung YB, Krishnan KR. EEG Predictors of Response to Brain Computer Interface Treatment in ADHD. Neuropsychopharmacology 2011, 36, S75–S197.
  20. Lee T, Goh L, Chong MS, Chua SM, Lei F, Lim WS, Chan M, Ng TP, Krishnan KR. Downregulation of TOMM40 expression in the blood of Alzheimer disease subjects compared with matched controls. J Psychiatr Res. 2012 Jun;46(6):828-30. doi: 10.1016/j.jpsychires.2012.03.006. Epub 2012 Apr 1
  21. Lee J, Goh L, Tan CH, Lee T. Analysis of blood-based gene expression signature in first episode psychosis. Psychiatry Res. 2012 Apr 12.
  22. Eid T, Behar K, Dhaher R, Bumanglag AV, Lee T. Roles of Glutamine Synthetase Inhibition in Epilepsy. Neurochem Res. 2012 Apr 10.
  23. Chong MS, Goh LK, Lim WS, Chan M, Tay L, Chen G, Feng L, Ng TP, Tan CH, Lee TS. Gene expression profiling of peripheral blood leukocytes shows consistent longitudinal downregulation of TOMM40 and upregulation of KIR2DL5A, PLOD1, and SLC2A8 among fast progressors in early Alzheimer's disease. J Alzheimers Dis. 2013 Jan 1;34(2):399-405.
  24. Eid T, Lee T, Wang Y, Perez E, Drummond J, Lauritzen F, Bergersen L, Meador-Woodruff J, Spencer D, de Lanerolle N, Cullum-Smith R. Gene expression of glutamate metabolizing enzymes in the hippocampal formation in human temporal lobe epilepsy. Epilepsia. 2013 Feb;54(2):228-38
  25. Lim CG, Lee TS, Guan C, Fung DS, Zhao Y, Teng SS, Zhang H, Krishnan KR. A brain-computer interface based attention training program for treating attention deficit hyperactivity disorder. PLoS One. 2012;7(10):e46692. doi: 10.1371/journal.pone.0046692. Epub 2012 Oct 24.
  26. Eid T, Tu N, Lee TS, Lai JC. Regulation of astrocyte glutamine synthetase in epilepsy. Neurochem Int. 2013 Jun 18.
  27. Lee T, Goh ASJ, Quek SY, Phillips R, Guan CT, Cheung YB, Feng L, Teng SZW, Wang CC, Zheng YC, Zhang HH, Ng TP, Lee J, Keefe R, Krishnan KKR. A Brain-computer Interface Based Cognitive Training System for Healthy Elderly: A Randomized Control Pilot Study for Usability and Preliminary Efficacy
  28. PLoSOne (in press) 2013 Nov 18;8(11):e79419. doi: 10.1371/journal.pone.0079419.
  29. Lee T, Quek SY, Krishnan KKR. Molecular imaging for Depressive Disorders. Am J Neuroradiology AJNR Am J Neuroradiol. 2014 Jun;35(6 Suppl):S44-54
  30. Lee T, Predictive Genetic Testing for Alzheimer’s disease. Ann Acad Med Singapore. 2014 September;43(9):437-8.
  31. Goh LK, Lim WS, Teo S, Vijayaraghavan A, Chan M, Tay L, Ng TP, Tan CH, Lee TS, Chong MS.TOMM40 Alterations in Alzheimer's Disease Over a 2-Year Follow-Up Period. J Alzheimers Dis. 2014 Sep 8.
  32. Eid T, Lee T. Reassessing the role of astrocytes in ammonia neurotoxicity. Nat Med. 2013 Dec;19(12):1572-4. doi: 10.1038/nm.3420.
  33. Lee T, Quek SY, Goh ASJ, Phillips R, Guan CT, Cheung YB, Feng L, Wang CC, Chin ZY, Zhang H, Lee J, Ng TP, KRR Krishnan.  A pilot randomized controlled trial using EEG-based Brain Computer Interface training for a Chinese-speaking group of healthy elderly. Clinical Interventions in Aging (in press).