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Psychiatry & Behavioral Science

Division of Neurobiology

Research Direction: Unraveling pathogenic mechanisms to advance novel therapeutics and biomarkers for neurodegeneration

Translational Neurobiology Laboratory

Welcome to the Translational Neurobiology Laboratory, where cutting-edge basic science meets real-world impact. Our research program is dedicated to advancing the field of neurobiology by focusing on therapeutics and biomarker development for neurodegenerative disorders with a focus on Huntington’s disease (HD) and Alzheimer’s disease (AD). We are a team of passionate researchers who are committed to bridging the gap between basic research and clinical applications to improve patient outcomes.

Recent research in the field of neurovascular and brain barrier has shed light on the crucial role of brain barriers and brain-immune interactions in maintaining brain health and its relevance in neurological diseases. Studies have identified novel mechanisms that regulate brain barrier integrity, including the role of specific cell types such as pericytes and astrocytes, as well as signaling pathways involving tight junction proteins and transporters. Furthermore, emerging research has highlighted the crosstalk between the neurovascular unit and immune cells, and how this interplay influences barrier function in neurodegenerative diseases. These findings have deepened our understanding of the complex interactions between the brain and cerebral vasculature and may have significant implications for the development of new therapeutic strategies for neurological disorders, including AD and HD.

As a part of the Division of Neurobiology, our interdisciplinary team of scientists work collaboratively to develop innovative therapeutic approaches and identify reliable biomarkers by incorporating these new research insights on brain barriers and brain immune interactions. We leverage cutting-edge techniques in molecular biology, genetics, neuroimaging, and computational analysis to unravel the intricate mechanisms underlying these neurological disorders and develop evidence-based interventions.

Our projects are performed in close collaborations with experts in a variety of fields, including Drs. Christopher Ross and Russell Margolis in translating our research findings into clinical care for HD patients; Drs. Michael Miller (Biomedical Engineering), Peter van Zijl, and Hanzhang Lu (Radiology) at Hopkins in developing innovative biomarkers by applying advanced MR imaging and cutting-edge technologies in computational analysis. Dr. Gene Yeo at UCSD in developing RNA-targeting gene therapy for HD. Drs Myriam Heiman and Manolis Kellis in using ScRNA-seq to dissect cell type specific contribution to neurovascular dysfunction in neurodegenerative disorders. Through our collaborative approach, we aim to bring breakthrough discoveries from the lab to the clinic in a timely and efficient manner, ultimately benefiting patients and their families.

Selected Publications

  1. Morelli KH, Wu Q, Gosztyla1 ML, Liu H, Yao M, Zhang C, Chen J, Marina RJ, Lee K, Jones KL, Huang M, Li A, Thompson LM, Duan W*, Yeo GW*. (*Corresponding authors). An RNA-targeting CRISPR-Cas13d system alleviates disease-related phenotypes in Huntington's disease models. Nature Neuroscience 2023 Jan;26(1):27-38. 
  2. Duan W, Urani E, Mattson MP. The potential of gene editing for Huntington's disease. Trends Neurosci. 2023 Mar 10:S0166-2236(23)00046-2. doi: 10.1016/j.tins.2023.02.005.
  3. Liu H, Chen L, Zhang C, Liu C, Li Y, Cheng L, Wei Z, Zhang Z, Lu H, van Zijl PCM, Iliff JJ, Xu J, Duan W. Interrogation of dynamic glucose-enhanced MRI and fluorescence-based imaging reveals a perturbed glymphatic network in Huntington’s disease. bioRxiv 2023.04.03.535397.
  4. Wei Z, Liu H, Lin Z, Yao M, Li R, Liu C, Li Y, Xu J, Duan W, Lu H. Non-contrast assessment of blood-brain barrier permeability to water in mice: An arterial spin labeling study at cerebral veins. Neuroimage. 2023 Mar;268:119870.
  5. Liu H, Zhang C, Xu J, Jin J, Cheng L, Miao X, Wu Q, Wei Z, Liu P, Lu H, van Zijl PCM, Ross CA, Hua J, Duan W. Huntingtin silencing delays onset and slows progression of Huntington's disease: a biomarker study. Brain 2021,144:3101-3113. 
  6. Jiang M, Zhang X, Liu H, LeBron J, Alexandris A, Peng Q, Gu H, Yang F, Li Y, Wang R, Hou Z, Arbez N, Ren Q, Dong J, Whela E, Wang R, Ratovitski T, Troncoso JC, Mori S, Ross CA, Lim J, Duan W. Nemo-like Kinase Reduces Mutant Huntingtin Levels and Mitigates Huntington’s Disease. Hum Mol Genet, 2020  May 28;29(8):1340-1352.
  7. Jin J, Peng Q, Hou Z, Jiang M, Wang X, Langseth AJ, Tao M, Barker PB, Mori S, Bergles DE, Ross CA, Detloff PJ, Zhang J, Duan W. Early white matter abnormalities, progressive brain pathology and motor deficits in a novel knock-in mouse model of Huntington’s disease. Hum Mol Genet 2015, 24(9):2508-2527.
  8. Jiang M, Wang J, Fu J, Du L, Jeong H, West T, Xiang L, Peng Q, Hou Z, Cai H, Seredenin T, Arbez N, Zhu S, Sommers K, Qian J, Zhang J, Mori S, Yang XW, Tamashiro KLK, Aja S, Moran TH, Luthi-Carter R, Martin B, Maudsley S, Mattson MP, Cichewicz RH, Ross CA, Holtzman DM, Krainc D, Duan W. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nature Medicine, 2012, 18(1): 153-158.