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 mechanism of BIN1 function in secretory autophagy, targeting this pathway with a new ASO-based therapy for Alzheimer's disease and related tauopathies.
| 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. |
| 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, 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*. "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. "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. |
The overarching goal for my laboratory is to understand the molecular and cellular fundamentals surrounding neurodegeneration and brain aging process with the aim of future translation into much-needed therapeutics. Departing from the neuron-centric convention, we have leveraged stem cell technology to employ multiple human brain cell types for studying their individual roles in the phenotypes of genes newly linked to AD and aging. Our team has also been using transgenic mouse models and collaborating with genomics experts to inform a wide range of molecular biology underlying disease mechanism. We are also planning to leverage the iPS models’ high-throughput potential to perform a molecule/drug screen targeting the new pathogenic knowledge from my lab in order to accelerate the development of an efficacious therapy for the looming medical crisis of AD in aging.
Early Career
Throughout my research career, I have explored new fields and demonstrated my ability to devise and innovate technologies for better approaches to uniquely address my questions. During my Neurology residency, I developed an original ultrasound technique to facilitate the diagnosis of Parkinson’s disease for better patient care (Huang et al., Mov Disord. 2007). For my thesis work, I investigated gene expression under cellular context of learning and memory, and I devised a microRNA tool to modulate protein synthesis, for which a patent has been issued (Huang et al., Cell 2012). As a postdoctoral scholar, I invented a stem cell-based human neuron growth system and discovered a signaling pathway that may account for the pathogenesis of AD contributed by the leading risk gene APOE (apolipoprotein E; Huang et al., Cell 2017). This work is well recognized and I was invited to share my perspectives on the utility of brain cellular models derived from induced pluripotent stem (iPS) cells for studying AD (Essayan-Perez et al., Neurobio Dis. 2019; correspondence). My currently funded NIH/NIA R00 grant allows me to characterize this apoE pathway in depth in its fundamental brain functions and to examine its potential use as a new therapeutic target.
Independent Career
I have assembled a vibrant research team from diverse research fields. Under my supervision, team members already are piloting new projects and making new discoveries. We continue to characterize the role of apoE signaling in the essential neuronal functions, and have published our unexpected findings showing the synapse formation in human neurons can be regulated in a manner corresponding to the disease risk predisposed by APOE (Huang et al., J Neurosci 2019; correspondence). We have developed an improved protocol to generate functional human oligodendrocytes with unprecedented efficiency from pluripotent stem cells (Assetta et al., submitted). Based on this technique, we have recently devised an original method to study the interactions between human neurons and oligodendrocyte lineage cells in the context of neurodegeneration and aging, with emphasis on the direct and rapid synaptic transmissions. In another umbrella project, we characterize the signaling functions mediated by CHI3L1 (YKL-40, top AD biomarker) in human astrocytes, which influence the inflammatory features underlying AD. In addition, our ongoing research endeavors further advance the technical establishments of iPSC and animal aging models. Specifically, we are reconstituting in vitro the blood-brain-barrier to investigate the contributions from systemic circulation to AD pathology, in collaboration with experts in bioengineering and living animals. I am confident that our results will jointly inform the pathogenesis from a distinctive perspective.
The Huang laboratory is currently funded by NIH/NIA (R00, R21 and R01), NIH COBRE in Rhode Island (Stem Cell and Aging Pilot Awards), Brown's OVPR Seed Awards and Carney Innovation Awards. Additionally, a postdoctoral fellowship (Alzheimer's disease) from the BrightFocus Foundation is actively supporting our research.
| 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
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 |
