Zhen Huang, PhD

Position title: Associate Professor, Neurology

PhD, Harvard University

Contact Information

Department of Neuroscience
University of Wisconsin
1111 Highland Avenue
Room 5505 WIMR-II
Madison, Wisconsin 53705
608.263.2469 Office
608.262.2469 Lab
z.huang@neurology.wisc.edu
Huang Lab

Research Statement

My lab is currently investigating how neuroinflammation regulates the inception and progression of sporadic Alzheimer’s disease (sAD), for the purpose of identifying and targeting key steps or mechanisms involved for treatment. sAD is a form of AD caused by primary neuroinflammation. It comprises >95% of all AD cases yet is much less well understood since, unlike familial AD, it is not linked to monogenic mutations. We study sAD by combining the analysis of curated human AD specimens with a novel sAD model we develop. This model, a unique resource, is the first model in AD research that recapitulates the stereotypic pattern of tauopathy and neurodegeneration initiation and spread in human sAD. Further, it also avoids artifacts and shortcomings of mutant gene expression in previous models since it only employs a microglia-specific loss of function mutation. By taking advantage of unique human and model resources, we are in the process of uncovering novel pathways and molecules involved in the most important steps of sAD development in humans for drug development.

We have also studied the development of the cerebral cortex at the several different levels of organization. We investigated how the organization arises during normal development and is affected in and contributes to brain neural and vascular diseases. To answer these questions, we employ mouse genetics and use tissue specific gene knockout technology. Among genes of interest to us is a gene involved in G protein coupled receptor (GPCR) signaling. We have found mutation in this gene, ric8a, which encodes a molecular chaperone and guanine nucleotide exchange factor (GEF) for heterotrimeric G proteins, result in cobblestone lissencephaly-like malformation or germinal matrix hemorrhage, depending on which brain cell types it is deleted from. These studies have provided major new insights into mechanisms through which cell-cell communication coordinates brain development and contributes to brain disease.

Selected Publications

PubMed

Kwon, H. J., Santhosh, D., & Huang, Z. (2024). A novel monomeric amyloid β-activated signaling pathway regulates brain development via inhibition of microglia. eLife, 13, RP100446. https://doi.org/10.7554/eLife.100446
Huang Z. (2024). Evidence that Alzheimer’s Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry. Journal of Alzheimer’s disease : JAD, 99(2), 447–470. https://doi.org/10.3233/JAD-240042
Santhosh, D., Sherman, J., Chowdhury, S., & Huang, Z. (2019). Harnessing region-specific neurovascular signaling to promote germinal matrix vessel maturation and hemorrhage prevention. Disease models & mechanisms, 12(11), dmm041228. https://doi.org/10.1242/dmm.041228
Huang Z. (2023). A Function of Amyloid-β in Mediating Activity-Dependent Axon/Synapse Competition May Unify Its Roles in Brain Physiology and Pathology. Journal of Alzheimer’s disease : JAD, 92(1), 29–57. https://doi.org/10.3233/JAD-221042
Ma, S., Santhosh, D., Kumar T, P., & Huang, Z. (2017). A Brain-Region-Specific Neural Pathway Regulating Germinal Matrix Angiogenesis. Developmental cell, 41(4), 366–381.e4. https://doi.org/10.1016/j.devcel.2017.04.014
Santhosh D, Huang Z. (2016) A Tie2-driven BAC-TRAP transgenic line for in vivo endothelial gene profiling. Genesis. 54(3):136-45. doi: 10.1002/dvg.22923.
Ma S, Huang Z. (2015) Neural Regulation of CNS Angiogenesis During Development. Frontiers in Biology. 10(1):61-73..
Boularan C, Hwang IY, Kamenyeva O, Park C, Harrison K, Huang Z, Kehrl JH. (2015) B Lymphocyte-Specific Loss of Ric-8A Results in a Gα Protein Deficit and Severe Humoral Immunodeficiency. Journal of Immunology. 195(5):2090-102. doi: 10.4049/jimmunol.1500523.
Santhosh D, Huang Z. (2015) Regulation of the nascent brain vascular network by neural progenitors. Mechanisms of Development. 138 Pt 1:37-42. doi: 10.1016/j.mod.2015.06.005.
Ma S, Kwon HJ, Johng H, Zang K, Huang Z. (2013) Radial glial neural progenitors regulate nascent brain vascular network stabilization via inhibition of Wnt signaling. PLoS Biology. 11(1):e1001469. doi: 10.1371/journal.pbio.1001469.