The research of Dr. He focuses on the neuropathogenesis in neurodegenerative diseases, including Alzheimer’s disease (AD) and Frontotemporal lobar degeneration (FTLD). He has been developing new disease research animal models with endogenous physiological protein transformed into pathological states as existing in patients’ brains. His group is aiming to use such more disease-relevant models for studying the pathogenesis mechanisms underlying neurodegenerative diseases, and identify the biomarkers and targets for early disease diagnoses and interventions.
Recently, through combining the clinical human AD brain tissue extracts and mouse models, he developed a novel AD model, and revealed an unknown association between two hallmark protein Ab and tau in AD pathogenesis (He et al., Nature Medicine, 2018). Further, he and colleagues developed a brand new FTLD model, and revealed the bases for pathological diversity in FTLD patients (He et al., Nature Communications, 2020).
Dr. He earned his B.Sc. in Biotechnology from Wuhan University (2005), followed by his Ph.D. in Neurobiology from Institute of Neuroscience, Chinese Academy of Sciences (CAS) (2012). Then he conducted his postdoctoral research with Drs. Virginia Lee and John Trojanowski at University of Pennsylvania to study neurodegenerative diseases. Since 2020, Dr. He has been leading an independent research group at Interdisciplinary Research Center on Biology and Chemistry (IRCBC), CAS to pursue his continuous interest in disease research.
Research Areas
Education
Postdoctoral Fellow: School of Medicine, University of Pennsylvania (2013-2019) Mentor: Virginia Lee
Ph.D.: Institute of Neuroscience, Chinese Academy of Sciences (2005-2012) Mentor: Yizheng Wang
B.S.: College of Life Sciences, Wuhan University (2001-2005)
Publications
Papers
Research articles:
17. Xu H, Qiu Q, Hu P, Hoxha K, Jang E, O'Reilly M, Kim C, He Z, Marotta N, Changolkar L, Zhang B, Wu H, Schellenberg GD, Kraemer B, Luk KC, Lee EB, Trojanowski JQ, Brunden KR, Lee VM*. MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons. Acta Neuropathol. 2024, PMID: 38472475.
16. Guo R.; Liu J.; Min X.; Zeng W.; Shan B.; Zhang M.; He Z.; Zhang Y.; He K.; Yuan J.; Xu D.*. Reduction of DHHC5-mediated Beclin 1 S-palmitoylation underlies autophagy decline in aging. Nat. Struct. Mol. Biol. 2024, PMID: 38177673.
15. Zhao X.#; Zeng W.#; Xu H.#; Sun Z.; Hu Y.; Peng B.; McBride, J.D.; Duan J.; Zhang B.; Kim S.J.; Zoll B.; Saito T.; Sasaguri H.; Saido T.C.; Ballatore C.; Yao H.; Wang Z.; Trojanowski J.Q.; Brunden K.R.; Lee V.M.Y.*; He Z.*. A microtubule stabilizer ameliorates protein pathogenesis and neurodegeneration in mouse models of repetitive traumatic brain injury. Sci. Transl. Med. 2023, PMID: 37703352.
14. Zhang S.;Zhu Y.; Lu J.; Liu Z.; Lobato A.G.; Zeng W.; Liu J.; Qiang J.; Zeng S.; Zhang Y.; Liu C.; Liu J.; He Z.; Zhai R.G.; Li D.*. Specific binding of Hsp27 and phosphorylated Tau mitigates abnormal Tau aggregation-induced pathology. ELife, 2022, PMID: 36048712.
13. Xu G.; Li Y.; Zhang S.; Peng H.; Wang Y.; Li D.; Jin T.; He Z.; Tong Y.; Qi C.; Wu G.; Dong K.; Gou J.; Liu Y.; Xiao T.; Qu J.; Li L.; Liu L.; Zhao P.; Zhang Z.; Yuan J. *. SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation. Cell Research, 2021, PMID: 34663909.
12. Darwich, N. F.; Phan, J. M.; Kim, B.; Suh, E.; Papatriantafyllou, J. D.; Changolkar, L.; Nguyen, A. T.; O'Rourke, C. M.; He, Z.; Porta, S.; Gibbons, G. S.; Luk, K. C.; Papageorgiou, S. G.; Grossman, M.; Massimo, L.; Irwin, D. J.; McMillan, C. T.; Nasrallah, I. M.; Toro, C.; Aguirre, G. K.; Van Deerlin, V. M.; Lee, E. B.*, Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau. Science 2020, PMID: 33004675.
11. Xu, D.; Zhao, H.; Jin, M.; Zhu, H.; Shan, B.; Geng, J.; Dziedzic, S. A.; Amin, P.; Mifflin, L.; Naito, M. G.; Najafov, A.; Xing, J.; Yan, L.; Liu, J.; Qin, Y.; Hu, X.; Wang, H.; Zhang, M.; Manuel, V. J.; Tan, L.; He, Z.; Sun, Z. J.; Lee, V. M. Y.; Wagner, G.; Yuan, J.*, Modulating TRADD to restore cellular homeostasis and inhibit apoptosis. Nature 2020, PMID: 32968279.
10. Weitzman, S. A.; Narasimhan, S.; He, Z.; Changolkar, L.; McBride, J. D.; Zhang, B.; Schellenberg, G. D.; Trojanowski, J. Q.; Lee, V. M. Y.*, Insoluble tau from human FTDP-17 cases exhibit unique transmission properties in vivo. J Neuropathol Exp Neurol 2020, PMID: 32838419.
9. He, Z.*; McBride, J. D.; Xu, H.; Changolkar, L.; Kim, S. J.; Zhang, B.; Narasimhan, S.; Gibbons, G. S.; Guo, J. L.; Kozak, M.; Schellenberg, G. D.; Trojanowski, J. Q.; Lee, V. M.*, Transmission of tauopathy strains is independent of their isoform composition. Nat Commun 2020, PMID: 31911587.
8. He, Z.; Guo, J. L.; McBride, J. D.; Narasimhan, S.; Kim, H.; Changolkar, L.; Zhang, B.; Gathagan, R. J.; Yue, C.; Dengler, C.; Stieber, A.; Nitla, M.; Coulter, D. A.; Abel, T.; Brunden, K. R.; Trojanowski, J. Q.; Lee, V. M.*, Amyloid-beta plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation. Nat Med 2018, PMID: 29200205.
7. Narasimhan, S.; Guo, J. L.; Changolkar, L.; Stieber, A.; McBride, J. D.; Silva, L. V.; He, Z.; Zhang, B.; Gathagan, R. J.; Trojanowski, J. Q.; Lee, V. M. Y.*, Pathological Tau Strains from Human Brains Recapitulate the Diversity of Tauopathies in Nontransgenic Mouse Brain. J Neurosci 2017, PMID: 29054878.
6. Guo, J. L.; Narasimhan, S.; Changolkar, L.; He, Z.; Stieber, A.; Zhang, B.; Gathagan, R. J.; Iba, M.; McBride, J. D.; Trojanowski, J. Q.; Lee, V. M.*, Unique pathological tau conformers from Alzheimer's brains transmit tau pathology in nontransgenic mice. J Exp Med 2016, PMID: 27810929.
5. Wang, J.; Lu, R.; Yang, J.; Li, H.; He, Z.; Jing, N.; Wang, X.; Wang, Y.*, TRPC6 specifically interacts with APP to inhibit its cleavage by gamma-secretase and reduce Abeta production. Nat Commun 2015, PMID: 26581893.
4. He, Z.; Jia, C.; Feng, S.; Zhou, K.; Tai, Y.; Bai, X.; Wang, Y.*, TRPC5 channel is the mediator of neurotrophin-3 in regulating dendritic growth via CaMKIIalpha in rat hippocampal neurons. J Neurosci 2012, PMID: 22764246.
3. Ding, X.#; He, Z.#; Zhou, K.#; Cheng, J.; Yao, H.; Lu, D.; Cai, R.; Jin, Y.; Dong, B.; Xu, Y.; Wang, Y.*, Essential role of TRPC6 channels in G2/M phase transition and development of human glioma. J Natl Cancer Inst 2010, PMID: 20554944.
2. Shi, Y.#; Ding, X.#; He, Z.#; Zhou, K. C.; Wang, Q.; Wang, Y. Z.*, Critical role of TRPC6 channels in G2 phase transition and the development of human oesophageal cancer. Gut 2009, PMID: 19651628.
1. Tai, Y.; Feng, S.; Ge, R.; Du, W.; Zhang, X.; He, Z.; Wang, Y.*, TRPC6 channels promote dendritic growth via the CaMKIV-CREB pathway. J Cell Sci 2008, PMID: 18559891.
Review articles:
5. Zhang T.; Cong L.; Chen B.; He Z.; Li G.; Qin Q. Editorial: Multimodal interventions in Alzheimer's disease: from basic research to clinical practice. Front Neurol 2023, PMID: 37928148
4. Han, Y.; He, Z.*, Concomitant protein pathogenesis in Parkinson's disease and perspective mechanisms. Front Aging Neurosci 2023, PMID: 37181621.
3. He, Z.*, TRPC Channel Downstream Signaling Cascades. Adv Exp Med Biol 2017, PMID: 28508310.
2. Feng, S.; He, Z.; Li, H.; Wang, Y.*, Ca(2+) signaling initiated by canonical transient receptor potential channels in dendritic development. Neurosci Bull 2015, PMID: 25732528.
1. Ding, X.; He, Z.; Shi, Y.; Wang, Q.; Wang, Y.*, Targeting TRPC6 channels in oesophageal carcinoma growth. Expert Opin Ther Targets 2010, PMID: 20235901.
#, Equal contribution; *, Corresponding author.