Shauna Yuan, M.D.

E-MAIL: [email protected]

Research Interests

The Yuan lab seeks to identify pathways and targets for the development of neurodegenerative disease therapeutics. Alzheimer’s disease pathogenesis is not wholly understood, and research is limited by difficulties in obtaining live neurons from patients, as well as an inability to comprehensively model the disease.  We meet these challenges through the use of induced pluripotent stem cell (iPSC) technology. IPSCs can be derived directly from adult tissues and guided to differentiate into various cell types to replace damaged tissue. Moreover, these cells hold great promise for preclinical research, as they offer the prospect of an unlimited amount of human neurons and glia (supporting brain cells) for drug testing.

The Yuan lab is particularly interested in the beginning stages of Alzheimer’s disease, and studies its early pathogenesis with a unique cell-surface sorting method for iPSCs.  This method enables the isolation and enrichment of highly purified neural stem cell, neuron, and glia populations.

One application of this powerful approach is our human neuronal model of tauopathy. Tauopathies—including Alzheimer’s disease—are neurodegenerative disorders that develop through the defective sorting and aggregation of tau protein. We aim to better understand the mechanisms of tau misfolding and aggregation by introducing disease-modeling gene mutations into neuronal cultures derived from human IPSCs.

This system provides a human in vitro model for studies of tauopathy-based neurodegeneration. Because Alzheimer’s disease can take decades to manifest in patients, we use iPSC technology to observe relevant phenotypes throughout the disease stages, and to test therapeutic drug compounds.

Publications

• Hemmy L, Cevasco-Trotter A, Silverman M, Wang S, Yuan SH. Music therapy interest in patients with Alzheimer's disease and Alzheimer's disease related dementia: A survey study. J Alzheimers Dis. 2026 May;111(2):890-896.
• Singh A, Babu S, Phan M, Yuan SH. CRISPR/Cas9-based protocol for precise genome editing in induced pluripotent stem cells. Bio Protoc. 2024 Dec 20;14(24):e5141.
• Wang SG, Cevasco-Trotter AM, Silverman MJ, Yuan SH. A narrative review of music therapy for neuropsychiatric symptoms in Alzheimer's disease and rationale for protocolized music teletherapy. Front Med (Lausanne). 2023 Nov 21;10:1248245. 
• Caldwell AB, Liu Q, Zhang C, Schroth GP, Galasko DR, Rynearson KD, Tanzi RE, Yuan SH, Wagner SL, Subramaniam S. Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease. Alzheimers Dement. 2022 Nov;18(11):2117-2130.
• Smedley GD, Walker KE, Yuan SH. The role of PERK in understanding development of neurodegenerative diseases. Int J Mol Sci. 2021 Jul 29;22(15):8146.
• Yuan SH, Hiramatsu N, Liu Q, Sun XV, Lenh D, Chan P, Chiang K, Koo EH, Kao AW, Litvan I, Lin JH. Tauopathy-associated PERK alleles are functional hypomorphs that increase neuronal vulnerability to ER stress. Hum Mol Genet. 2018 Nov 15;27(22):3951-3963. 
• Reilly P, Winston CN, Baron KR, Trejo M, Rockenstein EM, Akers JC, Kfoury N, Diamond M, Masliah E, Rissman RA, Yuan SH. Novel human neuronal tau model exhibiting neurofibrillary tangles and transcellular propagation. Neurobiol Dis. 2017 Oct;106:222-234.
• Liu Q, Waltz S, Woodruff G, Ouyang J, Israel MA, Herrera C, Sarsoza F, Tanzi RE, Koo EH, Ringman JM, Goldstein LS, Wagner SL, Yuan SH. Effect of potent γ-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers. JAMA Neurol. 2014 Dec;71(12):1481-9.

Current Graduate Students

Marcus Phan (Neuroscience, University of Minnesota)