Dr. Y. Alvin Huang, serving as the GLF Translational Assistant Professor of Molecular Biology, Cell Biology and Biochemistry at Brown University since July 2019, brings an extensive background in neurology and neuroscience to his research. He completed his M.D. and specialized neurology residency at National Taiwan University in Taipei, focusing on neurodegenerative disorders. He earned his Ph.D. in Neuroscience from Johns Hopkins University School of Medicine, investigating gene regulation within the context of memory formation. During his postdoctoral fellowship at Stanford University School of Medicine, Dr. Huang made significant advances in stem cell technologies and elucidated cellular mechanisms vital to brain function in both health and disease. His research currently centers on neuron-glial interactions in neurocognitive disorders such as Alzheimer's disease and Angelman syndrome, supported by innovative modeling tools his laboratory has developed.
A recipient of several prestigious academic awards, including the NIH Pathway to Independence Award, Dr. Huang is also the co-founder of Acre Therapeutics LLC. This startup is based on his team’s recent discovery of a novel disease mechanism in secretory autophagy, targeting this pathway with new drugs for Alzheimer's disease and related tauopathies, such as Progressive Supranuclear Palsy (PSP).
| Tsai WF, Yu RL, Chuang WL, Huang JF, Dai CY, Huang YA, Tan CH. "Association of CD33 genetic variants with neurocognitive profiles in chronic viral hepatitis." BJPsych open, vol. 11, no. 4, 2025, pp. e147. |
| Duckhorn J, Kim DK, Huang YA. "Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease." Neural regeneration research, 2025. |
| Yang X, Jiang W, Li Y, Lee CG, Elias JA, Tang C, Huang YA. "CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer's disease." Science Advances, vol. 11, no. 29, 2025, pp. eadv1492. |
| Palmer JE, Puri C, O'Rourke RS, Son SM, Sang C, Huang YA, Rubinsztein DC. "Coordination of autophagosome closure and release by the Alzheimer's disease-associated protein BIN1." Cell Reports, vol. 44, no. 9, 2025, pp. 116266. |
| Huie EZ, Yang X, Rioult-Pedotti MS, Tran K, Monsen ER, Hansen K, Erickson MA, Naik M, Yotova AY, Banks WA, Huang YA, Silverman JL, Marshall J. "Peptidomimetic inhibitors targeting TrkB/PSD-95 signaling improves cognition and seizure outcomes in an Angelman Syndrome mouse model." Neuropsychopharmacology, vol. 50, no. 5, 2025, pp. 772-782. |
| Yang X, Huang YA*, Marshall J* (* Correspondence). "UBE3A stabilization of β-catenin preserves synaptic proteins essential for motor and cognitive functions in Angelman Syndrome." Molecular autism, vol. 16, no. 1, 2025, pp. 60. |
| Yang X, Huang YA. "Unraveling the Roles of UBE3A in Neurodevelopment and Neurodegeneration." International Journal of Molecular Sciences, vol. 26, no. 5, 2025. |
| Kloske CM, Mahinrad S, Barnum CJ, Batista AF, Bradshaw EM, Butts B, Carrillo MC, Chakrabarty P, Chen X, Craft S, Da Mesquita S, Dabin LC, Devanand D, Duran-Laforet V, Elyaman W, Evans EE, Fitzgerald-Bocarsly P, Foley KE, Harms AS, Heneka MT, Hong S, Huang YA, Jackvony S, Lai L, Guen YL, Lemere CA, Liddelow SA, Martin-Peña A, Orr AG, Quintana FJ, Ramey GD, Rexach JE, Rizzo SJS, Sexton C, Tang AS, Torrellas JG, Tsai AP, van Olst L, Walker KA, Wharton W, Tansey MG, Wilcock DM. "Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference." Alzheimer's & Dementia, 2024. |
| Song Y, Jiang W, Afridi SK, Wang T, Zhu F, Xu H, Nazir FH, Liu C, Wang Y, Long Y, Huang YA, Qiu W, Tang C. "Astrocyte-derived CHI3L1 signaling impairs neurogenesis and cognition in the demyelinated hippocampus." Cell Reports, vol. 43, no. 5, 2024, pp. 114226. |
| Xu, Huiming, Jiang, Wei, Li, Xuejia, Jiang, Jiaohua, Afridi, Shabbir Khan, Deng, Longhui, Li, Rui, Luo, Ermei, Zhang, Zhaoqing, Huang, Yu-Wen Alvin, Cui, Yaxiong, So, Kwok-Fai, Chen, Haijia, Qiu, Wei, Tang, Changyong. "hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-κB signaling in an NMO mouse model." npj Regenerative Medicine, vol. 9, no. 1, 2024. |
| Yang X, Duckhorn J, Marshall J, Huang YA. "Interlinked destinies: How ubiquitin-proteasome and autophagy systems underpin neurocognitive outcomes." Experimental Neurology, vol. 379, 2024, pp. 114869. |
| Peng CS, Zhang Y, Liu Q, Marti GE, Huang YA, Südhof TC, Cui B, Chu S. "Nanometer-resolution tracking of single cargo reveals dynein motor mechanisms." Nature Chemical Biology, 2024. |
| Yang, Xin, Huang, Yu-Wen Alvin, Marshall, John. "Targeting TrkB-PSD-95 coupling to mitigate neurological disorders." Neural Regeneration Research, 2024. |
| Lau KA, Yang X, Rioult-Pedotti MS, Tang S, Jianan Zhang MA, Tian Y, Marino C, Yao M, Jiang Q, Tsuda AC, Huang YA, Cao C, Marshall J. "A PSD-95 peptidomimetic mitigates neurological deficits in a mouse model of Angelman Syndrome." Progress in neurobiology, 2023, pp. 102513. |
| O'Rourke R, Erdemir GA, Huang YA. "Assays of Monitoring and Measuring Autophagic Flux for iPSC-Derived Human Neurons and Other Brain Cell Types." Methods in Molecular Biology, vol. 2683, 2023, pp. 221-233. |
| Jiang W, Zhu F, Xu H, Xu L, Li H, Yang X, Khan Afridi S, Lai S, Qiu X, Liu C, Li H, Long Y, Wang Y, Connolly K, Elias JA, Lee CG, Cui Y, Huang YA*, Qiu W*, Tang C* (* Correspondence). "CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation." Science Advances, vol. 9, no. 39, 2023, pp. eadg8148. |
| Xu L, Xu H, Chen S, Jiang W, Afridi SK, Wang Y, Ren X, Zhao Y, Lai S, Qiu X, Huang YA, Cui Y, Yang H, Qiu W, Tang C. "Inhibition of complement C3 signaling ameliorates locomotor and visual dysfunction in autoimmune inflammatory diseases." Molecular therapy : the journal of the American Society of Gene Therapy, 2023. |
| Connolly K, Lehoux M, Assetta B, Huang YA. "Modeling Cellular Crosstalk of Neuroinflammation Axis by Tri-cultures of iPSC-Derived Human Microglia, Astrocytes, and Neurons." Methods in Molecular Biology, vol. 2683, 2023, pp. 79-87. |
| Walek KW, Stefan S, Lee JH, Puttigampala P, Kim AH, Park SW, Marchand PJ, Lesage F, Liu T, Huang YA, Boas DA, Moore C, Lee J. "Near-lifespan longitudinal tracking of brain microvascular morphology, topology, and flow in male mice." Nature Communications, vol. 14, no. 1, 2023, pp. 2982. |
| Lehoux M, Connolly K, Assetta B, Huang YA. "The Generation and Functional Characterization of Human Microglia-Like Cells Derived from iPS and Embryonic Stem Cells." Methods in Molecular Biology, vol. 2683, 2023, pp. 69-78. |
| Connolly K, Lehoux M, O'Rourke R, Assetta B, Erdemir GA, Elias JA, Lee CG, Huang YA. "Potential role of chitinase-3-like protein 1 (CHI3L1/YKL-40) in neurodegeneration and Alzheimer's disease." Alzheimer's & Dementia, vol. 19, no. 1, 2022, pp. 9-24. |
| Pak, ChangHui, Danko, Tamas, Mirabella, Vincent R., Wang, Jinzhao, Liu, Yingfei, Vangipuram, Madhuri, Grieder, Sarah, Zhang, Xianglong, Ward, Thomas, Huang, Yu-Wen Alvin, Jin, Kang, Dexheimer, Philip, Bardes, Eric, Mitelpunkt, Alexis, Ma, Junyi, McLachlan, Michael, Moore, Jennifer C., Qu, Pingping, Purmann, Carolin, Dage, Jeffrey L., Swanson, Bradley J., Urban, Alexander E., Aronow, Bruce J., Pang, Zhiping P., Levinson, Douglas F., Wernig, Marius, Südhof, Thomas C. "Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons." Proceedings of the National Academy of Sciences, 2021, pp. e2025598118. |
| Benedetta Assetta, Changyong Tang, Jing Bian, Ryan O'Rourke, Kevin Connolly, Thomas Brickler, Sundari Chetty, Yu-Wen Alvin Huang. "Generation of Human Neurons and Oligodendrocytes from Pluripotent Stem Cells for Modeling Neuron-Oligodendrocyte Interactions." Journal of visualized experiments : JoVE, 2020. |
| Huang, Yu-Wen Alvin*, Zhou, Bo, Nabet, Amber M., Wernig, Marius, Südhof, Thomas C*. (* Correspondence). "Differential Signaling Mediated by ApoE2, ApoE3, and ApoE4 in Human Neurons Parallels Alzheimer's Disease Risk." The Journal of Neuroscience, 2019, pp. 2994-18. |
| Essayan-Perez, Sofia, Zhou, Bo, Nabet, Amber M., Wernig, Marius, Huang, Yu-Wen Alvin. "Modeling Alzheimer’s disease with human iPS cells: advancements, lessons, and applications." Neurobiology of Disease, vol. 130, 2019, pp. 104503. |
| Huang, Yu-Wen Alvin, Zhou, Bo, Wernig, Marius, Südhof, Thomas C. "ApoE2, ApoE3, and ApoE4 Differentially Stimulate APP Transcription and Aβ Secretion." Cell, vol. 168, no. 3, 2017, pp. 427-441.e21. |
| Huang, Yu-Wen A., Ruiz, Claudia R., Eyler, Elizabeth C.H., Lin, Kathie, Meffert, Mollie K. "Dual Regulation of miRNA Biogenesis Generates Target Specificity in Neurotrophin-Induced Protein Synthesis." Cell, vol. 148, no. 5, 2012, pp. 933-946. |
| Tang, Sung-Chun, Huang, Yu-Wen, Shieh, Jiann-Shing, Huang, Sheng-Jean, Yip, Ping-Keung, Jeng, Jiann-Shing. "Dynamic cerebral autoregulation in carotid stenosis before and after carotid stenting." Journal of Vascular Surgery, vol. 48, no. 1, 2008, pp. 88-92. |
| Tsai, Chung-Fen, Wu, Ruey-Meei, Huang, Yu-Weng, Chen, Li-Ling, Yip, Ping-Keung, Jeng, Jiann-Shing. "Transcranial color-coded sonography helps differentiation between idiopathic Parkinson's disease and vascular parkinsonism." Journal of Neurology, vol. 254, no. 4, 2007, pp. 501-507. |
| Huang, Yu-Wen, Jeng, Jiann-Shing, Tsai, Chung-Fen, Chen, Li-Ling, Wu, Ruey-Meei. "Transcranial imaging of substantia nigra hyperechogenicity in a Taiwanese cohort of Parkinson's disease." Movement Disorders, vol. 22, no. 4, 2007, pp. 550-555. |
Our lab investigates how individual glial and neuronal cell types coordinate to shape cognition across neurodevelopment, brain aging, and neurodegeneration. Using human stem cell–derived neural systems, rodent models, and advanced bioengineering platforms, we dissect the cell-type–specific mechanisms that drive neurological disease. Our overarching goal is to translate these mechanistic insights into precise, cell-targeted therapeutic strategies for disorders including Alzheimer’s disease and Angelman syndrome.
Major Research Directions:
1) Astrocyte-centered: CHI3L1/YKL-40 and the Regulation of CNS Inflammation
Impact: Defining how astrocyte-derived CHI3L1/YKL-40 drives inflammatory signaling to reveal new intervention points in AD, autoimmune demyelination, and impaired neurogenesis.
We investigate how CHI3L1/YKL-40 modulates astrocyte reactivity, immune communication, and the inflammatory microenvironment across neurodegenerative and autoimmune contexts.
2) Microglia-centered: KLF2, APOE, and AD-Linked Mutations in 3D Hybrid Model Systems
Impact: Illuminating how microglial regulatory pathways shape aging, neuroinflammation, and synaptic dysfunction to uncover new microglia-targeted therapeutic avenues.
We study KLF2, APOE, and additional AD-relevant variants using a next-generation 3D hybrid human–rodent microglia model, enabling physiologically relevant dissection of microglial contributions to AD and brain aging.
3) Neuron-centered: BIN1 Control of Endosomal and Autophagic Homeostasis
Impact: Identifying neuronal BIN1-dependent pathways that drive tau spread and vulnerability, paving the way for BIN1-based therapeutics in Alzheimer’s disease.
We examine how BIN1 shapes endosomal trafficking, autophagy, and secretory dynamics, and how its disruption contributes to neuronal stress and tau pathology.
4) Oligodendrocyte-centered: UBE3A-Dependent Myelination Defects in Angelman Syndrome
Impact: Revealing how UBE3A loss impairs oligodendrocyte development to inform new myelin-focused therapeutic strategies for Angelman syndrome.
We investigate how UBE3A deficiency alters oligodendrocyte maturation, myelination, and circuit connectivity in this neurodevelopmental disorder.
The Huang laboratory has been funded by NIH/NIA (R00, R21 and R01), NIH COBRE in Rhode Island (Stem Cell and Aging Pilot Awards), Alzheimer's Association Strategic Fund, Foundation for Angelman Syndrome Therapeutics (FAST) TRAC Award, Brown's OVPR Seed Awards, Carney Innovation Awards and BBII Pilot Award.
| Year | Degree | Institution |
|---|---|---|
| 2012 | PhD | Johns Hopkins University |
| 2002 | MD | National Taiwan University |
| Residency | National Taiwan University Hospital, Neurology | - | Taipei, Taiwan |
| Postdoctoral Scholar | Stanford University School of Medicine, Molecular and Cellular Physiology | - | Stanford, CA |
2014-2015 Dean’s Postdoctoral Fellowship, Stanford University School of Medicine
2016 Alzheimer’s Association Award for Excellence in Research on Alzheimer’s and related disorders
2017-2022 K99/R00 Pathway to Independence Award, National Institute on Aging of NIH
2019 Junior Researcher Award, Japanese Neuroscience Society
2021 OVPR Seed Awards, Brown University
2021 Stem Cells and Aging Pilot Awards, NIH COBRE Institutions in Rhode Island
2022 Zimmerman Innovation Awards in Brain Science, Carney Institute, Brown University
2023 Blackman Family Fund for Multiple Sclerosis
2024 Richard B. Salomon Faculty Research Award, Brown University
2024 Junior Faculty Excellence in Mentoring Award, Carney Institute, Brown University
2025 Brown Biomedical Innovations to Impact (BBII) Pilot Award
2025 Innovation of the Year Award, Brown University Technology Innovations
Department of Molecular Biology, Cell Biology and Biochemistry
Department of Neurology
Carney Institute for Brain Science
Center for Translational Neuroscience in the Brown Institute for Translational Sciences
| BIOL 1540 - Molecular Genetics |
| BIOL 2540 - Molecular Genetics |
