Biology of tau, synucleins, TDP-43 and amyloid beta precursor proteins (APPs) in health and disease.
Alzheimer's disease; tauopathies; APP; Parkinson’s disease; synucleinopathies, amyotrophic lateral sclerosis, Frontotemporal lobar degeneration, TDP-43 proteinopathies.
Description of Research
Dr. Lee’s research focuses on disease proteins that form pathological inclusions in hereditary and sporadic Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders of aging. Her work demonstrated that tau, alpha-synuclein and TDP-43 proteins form unique brain aggregates in neurodegenerative diseases and provided critical evidence that aggregation of brain proteins is a common mechanistic theme in diverse neurodegenerative diseases including AD, PD, FTLD, ALS and related disorders. Significantly, Dr. Lee’s studies implicated the abnormal aggregation of tau, alpha-synuclein and TDP-43 in mechanisms that compromise neuronal viability. Most importantly, this research has opened up new avenues of research to identify targets for drug discovery to develop better treatments for these disorders.
Protein biochemistry; cell and molecular biology; monoclonal antibody production; immunochemical and immunocytochemical techniques; tissue culture; transgenic mouse models; and electron microscopy.
Lab rotation projects are difficult to define in a rapidly moving field. Please contact Dr. Lee to discuss possible rotation projects.
Cohen TJ, Hwang AW, Restrepo C, Yuan CX, Trojanowski JQ, Lee VM-Y. : An acetylation switch controls TDP-43 function and aggregation propensity. Nat Commun 6: 5845, 2015.
Goosens J, Vanmechelen E, Trojanowski JW, Lee VM, Van Broeckhoven C, van der Zee J, Engelborghs S. : TDP-43 as a possible biomarkers for frontotemporal lobar degeneration: a systematic review of existing antibodies. Acta Neuropathol Commun. 3: 15, 2015.
Porta S, Kwong LK, Trojanowski JQ, Lee VM: Drosha Inclusions Are New Components of Dipeptide-Repeat Protein Aggregates in FTLD-TDP and ALS C9orf72 Expansion Cases. J Neuropathol Exp Neurol
74: 380-387, 2015.
Brettschneider J, Del Tredici K, Lee VM, Trojanowski JQ.: Spreading of pathology in neurodegenerative diseases: a focus on human studies. Nat Rev Neurosci 16: 109-120, 2015.
Ballatore C, Gay B, Huang L, Robinson KH, James MJ, Trojanowski JQ, Lee VM-Y, Brunden KR, Smith AB 3rd. : Evaluation of the cyclopentane-1,2-dione as a potential bio-isostere of the carboxylic acid functional group. Bioorg Med Chem Lett 24: 4171-4175, 2014.
Crescenzi R, DeBrosse C, Nanga RP, Reddy S, Haris M, Hariharan H, Iba M, Lee VM-Y, Detre JA, Borthakur A, Reddy R. : In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy. Neuroimage 101C: 185-192, 2014.
Peeraer E, Bottelvergs A, Van Kolen K, Mahieu M, Duyschaever H, Verdonck L, Torremans A, Sluydts E, Van Acker N, Kemp JA, Brunden KR, Trojanowski JQ, Dewachter I, Lee VM-Y, Moechars D. : Intracerebral injection of preformed synthetic tau fibrils initiates widespread tauopathy and neuronal loss in the brains of tau transgenic mice. Neurobiol Dis 73: 83-95, 2014.
Boluda S, Toledo JB, Irwin DJ, Raible KM, Byrne MD, Lee EB, Lee VM-Y, Trojanowski JQ: A comparison of Aβ amyloid pathology staging systems and correlation with clinical diagnosis. Acta Neuropath 128: 543-550, 2014.
Ballatore C, Smith AB 3rd, Lee VM-Y, Trojanowski JQ, Brunden KR. : Aminothienopyridazines as imaging probes of tau pathology: a patent evaluation of WO2013090497. Expert Opin Ther Pat 24: 355-360, 2014.
Tran HT, Chung CH, Luk KC, Iba M, Zhang B, Trojanowski JQ, Lee VM-Y. : α-Synuclein immunotherapy blocks uptake and templated propagation of misfolded α-Synuclein and neurodegeneration. Cell Reports 72: 1-12, 2014.
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Last updated: 01/12/2017
The Trustees of the University of Pennsylvania