Cure Alzheimer's Fund Cure Alzheimer's Fund

Shane Liddelow, Ph.D.

Associate Professor, Department of Neuroscience and Physiology; Associate Professor, Department of Ophthalmology; Neuroscience Institute at New York University Langone Health

 

Shane Liddelow is an associate professor in the Neuroscience Institute and Department of Neuroscience and Physiology at the New York University Langone Health. His research is focused on understanding the interactions between glial cells and neuron degeneration and dysfunction, and what molecules modulate these interactions.

Dr. Liddelow earned his Bachelors of Science (Hons) and Biomedical Science from the University of Melbourne, Australia, majoring in Neuroscience and Anatomy & Cell Biology. His Ph.D. in Pharmacology (also at the University of Melbourne, Australia) with Norman Saunders and Katarzyna Dziegielewska was in the area of the developing blood-brain and blood-cerebrospinal fluid barriers. In his postdoctoral work with Ben Barres at Stanford University, he discovered a close association between astrocytes (the major cell type in the brain), microglia (the resident immune cells of the brain), and abnormal neuron function. This research highlights that one form of reactive astrocyte is induced by factors released by microglia and that these reactive astrocytes release a toxic factor that kills specific subtypes of neurons. When looking at human patients he showed that neurotoxic reactive astrocytes are localized to regions of neurodegeneration in Alzheimer’s disease (AD), and are a common form of reactivity among many other neurodegenerative diseases.

In 2018, Dr. Liddelow established his own independent laboratory in the Neuroscience Institute at NYU Langone. He is continuing to investigate the role that reactive astrocytes play in the initiation and progression of AD. He is pioneering the development of novel in vitro and in vivo models of astrocyte reactivity which properly recapitulate human disease states – allowing for new investigations into glial dysfunction in neurodegenerative disease and in normal aging.

To lean more, visit Dr. Liddelow’s social media page, as well as the pages of the Neuroscience Institute at NYU Langone Health and NYU Grossman School of Medicine.

Related Research:

Neuroimmune Consortium: Astrocyte Inflammatory Contributions to Alzheimer’s Disease Shane Liddelow 2024-03-18 Mechanisms of Astrocyte-Derived Lipid Toxicity in Alzheimer’s Disease Shane Liddelow 2023-12-08 The Role of Astrocyte-Derived Toxic Lipids Mediating Degeneration in Alzheimer’s Disease Shane Liddelow 2022-02-15 Neuroimmune Consortium: Investigation of Alzheimer’s Disease Risk Alleles in Astrocytes—Focus on Cholesterol Transport and Microglia Interactions Shane Liddelow 2020-12-15 Neurotoxic Reactive Astrocytes in Alzheimer’s Disease Shane Liddelow 2018-07-24

Funded Research

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

Project Description Researchers Funding
Neuroimmune Consortium: Astrocyte Inflammatory Contributions to Alzheimer’s Disease 2024

$287,500
Mechanisms of Astrocyte-Derived Lipid Toxicity in Alzheimer’s Disease 2023

$208,033
The Role of Astrocyte-Derived Toxic Lipids Mediating Degeneration in Alzheimer’s Disease 2021, 2022

$349,637
Neuroimmune Consortium: Investigation of Alzheimer’s Disease Risk Alleles in Astrocytes—Focus on Cholesterol Transport and Microglia Interactions 2020-2022

$615,000
Neurotoxic Reactive Astrocytes in Alzheimer’s Disease 2018-2019

$500,000

Selected Publications

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

Prescott, K., Münch, A. E., Brahms, E., Weigel, M. K., Inoue, K., Buckwalter, M. S., Liddelow, S. A., & Peterson, T. C. Blocking of microglia-astrocyte proinflammatory signaling is beneficial following stroke, Frontiers in Molecular Neuroscience, January 4, 2024, Read More

Prakash, P., Erdjument-Bromage, H., O'Dea, M. R., Munson, C. N., Labib, D., Fossati, V., Neubert, T. A., & Liddelow, S. A. Proteomic profiling of interferon-responsive reactive astrocytes in rodent and human, Glia, November 30, 2023, Read More

Frazel, P. W., Labib, D., Fisher, T., Brosh, R., Pirianian, N., Marchildon, A., Boeke, J. D., Fossati, V., & Liddelow, S. A. Longitudinal scRNA-seq analysis in mouse and human informs optimization of rapid mouse astrocyte differentiation protocols, Nature Neuroscience, September 11, 2023, Read More

Castranio, E. L., Hasel, P., Haure-Mirande, J. V., Ramirez Jimenez, A. V., Hamilton, B. W., Kim, R. D., Glabe, C. G., Wang, M., Zhang, B., Gandy, S., Liddelow, S. A., & Ehrlich, M. E. Microglial INPP5D limits plaque formation and glial reactivity in the PSAPP mouse model of Alzheimer’s disease, Alzheimer's & Dementia, November 30, 2022, Read More

Titus, H. E., Xu, H., Robinson, A. P., Patel, P. A., Chen, Y., Fantini, D., Eaton, V., Karl, M., Garrison, E. D., Rose, I. V. L., Chiang, M. Y., Podojil, J. R., Balabanov, R., Liddelow, S. A., Miller, R. H., Popko, B., & Miller, S. D. Repurposing the cardiac glycoside digoxin to stimulate myelin regeneration in chemically-induced and immune-mediated mouse models of multiple sclerosis, Glia, July 9, 2022, Read More

Fernández-Castañeda, A., Lu, P., Geraghty, A. C., Song, E., Lee, M. H., Wood, J., … Liddelow, S. A., … Monje, M. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation, Cell, June 13, 2022, Read More

Labib, D., Wang, Z., Prakash, P., Zimmer, M., Smith, M. D., Frazel, P. W., Barbar, L., Sapar, M. L., Calabresi, P. A., Peng, J., Liddelow, S. A., & Fossati, V. Proteomic Alterations and Novel Markers of Neurotoxic Reactive Astrocytes in Human Induced Pluripotent Stem Cell Models, Frontiers in Molecular Neuroscience, May 3, 2022, Read More

Kleffman, K., Levinson, G., Rose, I., Blumenberg, L. M., … Li, Y. M., … Liddelow, S.A., … Hernando, E. Melanoma-Secreted Amyloid Beta Suppresses Neuroinflammation and Promotes Brain Metastasis, Cancer Discovery, May 2, 2022, Read More

Sadick, J. S., O'Dea, M. R., Hasel, P., Dykstra, T., Faustin, A., & Liddelow, S. A. Astrocytes and oligodendrocytes undergo subtype-specific transcriptional changes in Alzheimer’s disease., Neuron, April 4, 2022, Read More

Bandler, R. C., Vitali, I., Delgado, R. N., Ho, M. C., Dvoretskova, E., Ibarra Molinas, J. S., Frazel, P. W., Mohammadkhani, M., Machold, R., Maedler, S., Liddelow, S. A., Nowakowski, T. J., Fishell, G., & Mayer, C. Single-cell delineation of lineage and genetic identity in the mouse brain, Nature, December 15, 2021, Read More

Guttenplan, K. A., Weigel, M. K., Prakash, P., Wijewardhane, P. R., Hasel, P., Rufen-Blanchette, U., Münch, A. E., Blum, J. A., Fine, J., Neal, M. C., Bruce, K. D., Gitler, A. D., Chopra, G., Liddelow, S. A., & Barres, B. A. Neurotoxic reactive astrocytes induce cell death via saturated lipids., Nature, October 6, 2021, Read More

Hasel, P., Rose, I. V. L., Sadick, J. S., Kim, R. D., & Liddelow, S. A. Neuroinflammatory astrocyte subtypes in the mouse brain, Nature Neuroscience, August 19, 2021, Read More

Prakash, P., Jethava, K. P., Korte, N., Izquierdo, P., Favuzzi, E., Rose, I. V. L., Guttenplan, K. A., Manchanda, P., Dutta, S., Rochet, J. C., Fishell, G., Liddelow, S. A., Attwell, D., & Chopra, G. Monitoring phagocytic uptake of amyloid beta into glial cell lysosomes in real time, Chemical Science, July 21, 2021, Read More

Spanos, F., & Liddelow, S. A. An Overview of Astrocyte Responses in Genetically Induced Alzheimer’s Disease Mouse Models, Cells, November 4, 2020, Read More

Zhang, J., Velmeshev, D., Hashimoto, K., Huang, Y. H., Hofmann, J. W., Shi, X., Chen, J., Leidal, A. M., Dishart, J. G., Cahill, M. K., Kelley, K. W., Liddelow, S. A., … Huang, E. J. Neurotoxic microglia promote TDP-43 proteinopathy in progranulin deficiency, Nature, August 31, 2020, Read More

Liddelow, S. A., Marsh, S. E., & Stevens, B. Microglia and Astrocytes in Disease: Dynamic Duo or Partners in Crime?, Trends in Immunology, August 17, 2020, Read More

Guttenplan, K. A., Weigel, M. K., Adler, D. I., Couthouis, J., Liddelow, S. A., Gitler, A. D., & Barres, B. A. Knockout of reactive astrocyte activating factors slows disease progression in an ALS mouse model, Nature Communications, July 27, 2020, Read More

Guttenplan, K. A., Stafford, B. K., El-Danaf, R. N., Adler, D. I., Münch, A. E., Weigel, M. K., Huberman, A. D., & Liddelow, S. A. Neurotoxic Reactive Astrocytes Drive Neuronal Death After Retinal Injury, Cell Reports, June 23, 2020, Read More

Barbar, L., Jain, T., Zimmer, M., Kruglikov, I., Sadick, J. S., Wang, M., Kalpana, K., Rose, I. V. L., Burstein, S. R., Rusielewicz, T., Nijsure, M., Guttenplan, K. A., di Domenico, A., Croft, G., Zhang, B., Nobuta, H., Hébert, J. M., Liddelow, S. A., & Fossati, V. CD49f Is a Novel Marker of Functional and Reactive Human iPSC-Derived Astrocytes, Neuron, June 1, 2020, Read More

Sadick, J. S., Crawford, L. A., Cramer, H. C., 3rd, Franck, C., Liddelow, S. A., & Darling, E. M. Generating Cell Type-Specific Protein Signatures from Non-symptomatic and Diseased Tissues, Annals of Biomedical Engineering, April 17, 2020, Read More

Gibson, E. M., Nagaraja, S., Ocampo, A., Tam, L. T., Wood, L. S., Pallegar, P. N., Greene, J. J., Geraghty, A. C., Goldstein, A. K., Ni, L., Woo, P. J., Barres, B. A., Liddelow, S., Vogel, H., & Monje, M. Methotrexate Chemotherapy Induces Persistent Tri-glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment, Cell, December 6, 2018, Read More

Shi, Y., Yamada, K., Liddelow, S. A., Smith, S. T., Zhao, L., Luo, W., Tsai, R. M., Spina, S., Grinberg, L. T., Rojas, J. C., Gallardo, G., Wang, K., Roh, J., Robinson, G., Finn, M. B., Jiang, H., Sullivan, P. M., Baufeld, C., Wood, M. W., Sutphen, C., McCue, L., Xiong, C., Del-Aquila, J.L., Morris, J.C., Cruchage, C., Alzheimer's Disease Neuroimaging Initiative, Fagan, A.M., Miller, B.L., Boxer, A.L., Seeley, W.W., Butovsky, O., Barres, B.B., Paul, S.M., & Holtzman, D.M. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathy, Nature, September 28, 2017, Read More

Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W. S., Peterson, T. C., Wilton, D. K., Frouin, A., Napier, B. A., Panicker, N., Kumar, M., Buckwalter, M. S., Rowitch, D. H., Dawson, V. L., Dawson, T. M., Stevens, B., Barres, B. A. Neurotoxic reactive astrocytes are induced by activated microglia, Nature, January 18, 2017, Read More

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