Dr. Y. Alvin Huang is the GLF Translational Assistant Professor of Molecular Biology, Cell Biology and Biochemistry, joining the faculty of Brown Biology and Medicine in July, 2019. He acquired his M.D. and Neurology residency from National Taiwan University, Taipei, Taiwan, sub-specializing in neurodegenerative disorders. His Ph.D. in Neuroscience was received from Johns Hopkins University School of Medicine, where he studied the gene regulation in the context of memory formation. For his postdoctoral fellowship at Stanford University School of Medicine (mentored by Dr. Thomas Südhof), he innovated stem cell technologies and uncovered cellular mechanisms important for brain functions in health and in disease. His current research focuses on molecular biology of Alzheimer's disease and aging, aided by new modeling tools developed in his laboratory. He is the recipient of several academic awards, including the NIH Pathway to Independence Award.
|Pak, ChangHui, Danko, Tamas, Mirabella, Vincent R., Wang, Jinzhao, Zhang, Xianglong, Ward, Thomas, Grieder, Sarah, Vangipuram, Madhuri, Huang, Yu-Wen Alvin, Liu, Yingfei, Jin, Kang, Dexheimer, Philip, Bardes, Eric, Mittelpunkt, Alexis, Ma, Junyi, McLachlan, Michael, Moore, Jennifer C., Urban, Alexander E., Dage, Jeffrey L., Swanson, Bradley J., 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." , 2020.|
|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, Y.A., Meffert, M.K., Ruiz, C.R., Eyler, E.C.
"Expression Construct for a Lin28-Resistant Let-7 Precursor microRNA." 2013.
|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.
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.
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.
NIH/NIA R00 AG054616 (PI: Huang). 07/01/2019–06/30/2022
Title: A molecular signaling pathway underlying differential predisposition of ApoE4 genotype to Alzheimer's disease.
The overall objective application is to determine whether and how ApoE4-specific activation of DLK/MAPK signaling pathway may account for ApoE4’s deleterious AD-promoting effect.
|Postdoctoral Scholar||Stanford University School of Medicine, Molecular and Cellular Physiology||-||Stanford, CA 94305|
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
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