Huaxi Xu, Ph.D.

Jeanne and Gary Herberger Leadership Chair in Neuroscience Research; Professor and Director, Neuroscience Initiative, Sanford Burham Prebys Medical Discovery Institute

Dr. Huaxi Xu, Jeanne & Gary Herberger Leadership Chair and Director of Neuroscience Initiative at Sanford Burnham Prebys Medical Discovery Institute (SBP), is an expert specialized in the molecular mechanisms of Alzheimer’s disease (AD). His research is focused on the regulation of APP processing and trafficking, and mechanisms of synaptic dysfunction and neurotoxicity induced by proteotoxic beta amyloid and neurofibrillary tangle (NFT) tau components. Dr. Xu’s laboratory has also engaged in pioneering research in investigating novel genes and pathways involved in neuronal function/dysfunction and cell death and integrating their cellular function to the pathogenesis of neurodegenerative diseases such as AD, Down syndrome and Progressive Supranuclear Palsy. To this end, his laboratory is also developing animal models to study neuronal and microglial function in relation to neurodegenerative dysfunction. As an independent PI with over 20 years’ experience, Dr. Xu has continuously received funding of multiple grants from the NIH and many private foundations and published over 150 papers with a total impact factor of ~1100 (with ~12,000 citations and an h-index >55).

Dr. Xu received his Ph.D. degree from Albert Einstein College of Medicine under joint supervision from Dennis Shields and Gunter Blobel (1999 Laureate of the Nobel Prize in Physiology or Medicine); his thesis studies focused on the intracellular trafficking and proteolytic processing of membrane proteins. Dr. Xu completed his postdoctoral studies at The Rockefeller University, where he was appointed assistant professor in 1998 in the laboratory of Paul Greengard (2000 Laureate of the Nobel Prize in Physiology or Medicine), where he carried out a variety of research projects characterizing signal transduction pathways in the central nervous system. Dr. Xu moved to SBP as associate professor in 2003 and was promoted to full professor in 2008; he also served as Neurodegenerative Disease Research Program Director from 2007-2012. Together with Dr. Guojun Bu (Mayo Clinic), Dr. Xu established the well-respected neuroscience journal, Molecular Neurodegeneration (with a 5-yr impact factor of 7.077), which has become one of the top-ranking scientific journals in the neuroscience field.



Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Stupack, J., Xiong, X. P., Jiang, L. L., Zhang, T., Zhou, L., Campos, A., Ranscht, B., Mobley, W., Pasquale, E. B., Xu, H., & Huang, T. Y. Soluble SORLA enhances neurite outgrowth and regeneration through activation of the EGF Receptor/ERK signaling axis, Journal of Neuroscience, June 29, 2020, Read More

Jiang, L. L., Zhu, B., Zhao, Y., Li, X., Liu, T., Pina-Crespo, J., Zhou, L., Xu, W., Rodriguez, M. J., Yu, H., Cleveland, D. W., Ravits, J., Da Cruz, S., Long, T., Zhang, D., Huang, T. Y., & Xu, H. Membralin deficiency dysregulates astrocytic glutamate homeostasis leading to ALS-like impairment, Journal of Clinical Investigation, May 21, 2019, Read More

Liu T, Zhu B, Liu Y, Zhang X, Yin J, Li X, Jiang L, Hodges AP, Rosenthal SB, Zhou L, Yancey J, McQuade A, Blurton-Jones M, Tanzi RE, Huang TY, Xu H. Multi-omic comparison of Alzheimer’s variants inhuman ESC–derived microglia reveals convergence at APOE, Journal of Experimental Medicine, September 17, 2020, Read More

Zhu, B., Jiang, L., Huang, T., Zhao, Y., Liu, T., Zhong, Y., Li, X., Campos, A., Pomeroy, K., Masliah, E., Zhang, D., & Xu, H. ER-associated degradation regulates Alzheimer’s amyloid pathology and memory function by modulating gamma-secretase activity, Nature Communications, November 13, 2017, Read More

Zhu B, Liu Y, Hwang S, Archuleta K, Huang H, Campos A, Murad R, Piña-Crespo J, Xu H, Huang TY. Trem2 deletion enhances tau dispersion and pathology through microglia exosomes, Molecular Neurodegeneration, September 2, 2022, Read More

Zhong L, Zhang ZL, Li X, Liao C, Mou P, Wang T, Wang Z, Wang Z, Wei M, Xu H, Bu G, Chen XF. TREM2/DAP12 Complex Regulates Inflammatory Responses in Microglia via the JNK Signaling Pathway, Frontiers in Aging Neuroscience, June 21, 2017, Read More

Wang X, Zhou Y, Wang J, Tseng IC, Huang T, Zhao Y, Zheng Q, Gao Y, Luo H, Zhang X, Bu G, Hong W, Xu H. SNX27 Deletion causes hydrocephalus by impairing ependymal cell differentiation and ciliogenesis, Journal of Neuroscience, December 14, 2016, Read More

Zhuang, K., Huang, C., Leng, L., Zheng, H., Gao, Y., Chen, G., Ji, Z., Sun, H., Hu, Y., Wu, D., Shi, M., Li, H., Zhao, Y., Zhang, Y., Xue, M., Bu, G., Huang, T. Y., Xu, H., & Zhang, J. Neuron-specific menin deletion leads to synaptic dysfunction and cognitive impairment by modulating p35 experssion, Cell Reports, July 17, 2018, Read More

Zhao, Y., Wu, X., Li, X., Jiang, L. L., Gui, X., Liu, Y., Sun, Y., Zhu, B., Piña-Crespo, J. C., Zhang, M., Zhang, N., Chen, X., Bu, G., An, Z., Huang, T. Y., & Xu, H. TREM2 is a receptor for beta-amyloid that mediates microglia function, Neuron, March 7, 2018, Read More

Lee, C. Y. D., Daggett, A., Gu, X., Jiang, L. L., Langfelder, P., Li, X., Wang, N., Zhao, Y., Park, C. S., Cooper, Y., Ferando, I., Mody, I., Coppola, G., Xu, H., & Yang, X. W. Elevated TREM2 gene dosage reprograms microglia responsivity and ameliorates pathologicla phenotypes in Alzheimer’s disease models, Neuron, March 7, 2018, Read More

Simandi Z, Pajer K, Karolyi K, Sieler T, Jiang LL, Kolostyak Z, Sari Z, Fekecs Z, Pap A, Patsalos A, Contreras GA, Reho B, Papp Z, Guo X, Horvath A, Kiss G, Keresztessy Z, Vámosi G, Hickman J, Xu H, Dormann D, Hortobagyi T, Antal M, Nógrádi A, Nagy L. Arginine Methyltransferase PRMT8 provides cellular stress tolerance in aging motoneurons, Journal of Neuroscience, August 29, 2018, Read More

Du, Y., Zhao, Y., Li, C., Zheng, Q., Tian, J., Li, Z., Huang, T. Y., Zhang, W., & Xu, H. Inhibition of PKC delta reduces amyloid-beta levels and reverses Alzheimer’s disease phenotypes, Journal of Experimental Medicine, May 8, 2018, Read More

Huang, T. Y., Zhao, Y., Jiang, L. L., Li, X., Liu, Y., Sun, Y., Piña-Crespo, J. C., Zhu, B., Masliah, E., Willnow, T. E., Pasquale, E. B., & Xu, H. SORLA attenuates EphA4 signaling and amyloid beta-induced neurodegeneration, Journal of Experimental Medicine, December 4, 2017, Read More

Xie, Y., Niu, M., Ji, C., Huang, T. Y., Zhang, C., Tian, Y., Shi, Z., Wang, C., Zhao, Y., Luo, H., Can, D., Xu, H., Zhang, Y. W., & Zhang, X. SNX8 Enhances Non-Amyloidogenic APPP Trafficking and Attenuates A beta Accumulation and Memory Deficits in an AD mouse, Frontiers in Cellular Neuroscience, September 6, 2019, Read More

Zheng, Q., Huang, T., Zhang, L., Zhou, Y., Luo, H., Xu, H., & Wang, X. Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases, Frontiers in Aging Neuroscience, December 15, 2016, Read More

Zhang, C., Tan, Z., Xie, Y., Zhao, Y., Huang, T. Y., Lu, Z., Luo, H., Can, D., Xu, H., Zhang, Y. W., & Zhang, X. Appoptosin mediates lesions induced by oxidative stress through the JNK-FoxO1 Pathway, Frontiers in Aging Neuroscience, September 4, 2019, Read More

Zhang, H., Huang, T., Hong, Y., Yang, W., Zhang, X., Luo, H., Xu, H., & Wang, X. The retromer complex and sorting nexins in neurodegenerative diseases, Frontiers in Aging Neuroscience, March 26, 2018, Read More

Painter, M. M., Atagi, Y., Liu, C. C., Rademakers, R., Xu, H., Fryer, J. D., & Bu, G. TREM2 in CNS homeostasis and neurodegenerative disease, Molecular Neurodegeneration, September 4, 2015, Read More

Zhong, L., Chen, X. F., Wang, T., Wang, Z., Liao, C., Wang, Z., Huang, R., Wang, D., Li, X., Wu, L., Jia, L., Zheng, H., Painter, M., Atagi, Y., Liu, C. C., Zhang, Y. W., Fryer, J. D., Xu, H., & Bu, G. Soluble TREM2 induces inflammatory responses and enhnaces microglial survival, Journal of Experimental Medicine, March 6, 2017, Read More

Zhong, L., Wang, Z., Wang, D., Wang, Z., Martens, Y. A., Wu, L., Xu, Y., Wang, K., Li, J., Huang, R., Can, D., Xu, H., Bu, G., & Chen, X. F. Amyloid-beta modulates microglial responses by binding to the triggering receptor expressed on myeloid cells 2 (TREM2), Molecular Neurodegeneration, March 27, 2018, Read More