WHAT WE DO

What do reactive astrocytes (REALLY) do?

Astrocytes are among the most abundant cells in the mammalian central nervous system (CNS). They are integral to brain and spinal-cord physiology and perform many functions important for normal neuronal development, synapse formation, and proper propagation of action potentials. We still know very little, however, about how these functions change in response to immune attack, chronic neurodegenerative disease, or acute trauma.

Our work focuses on the mechanisms that induce different forms of reactive astrocytes, and how these reactive cells interact with other cells in the CNS in a positive or negative way. We use high throughput single cell and bulk RNA sequencing, and spatial transcriptomics to investigate the heterogeneity of astrocytes in multiple species. We also take advantage of genetic engineering and modern in vitro modeling to interrogate disease mechanisms and interaction with other CNS cells that change between health and disease.

We aim to apply this knowledge to reactive astrocytes in human disease, and believe that the discovery of astrocytes with different reactive states has important implications for the development of new therapies for CNS injury and diseases.

Ultimately, we aim to provide a more comprehensive understanding of what astrocytes do in disease and how we might ameliorate disease by targeting astrocytes.

We are forever grateful to those who fund our work, including the National Institutes of Health (National Eye Institute, National Institute of Neurological Disorders and Stroke), the Cure Alzheimer’s Fund, MD Anderson Neurodegeneration Consortium, the Alzheimer’s Association, the Carol and Gene Ludwig Family Foundation, the National Multiple Sclerosis Society, the Collaborative Center for X-Linked Dystonia-Parkinsonism at Mass General Hospital, Howard Hughes Medical Institute, the Pershing Square Foundation MIND Prize, and NYU School of Medicine.

We also work closely with the Parekh Center for Interdisciplinary Neurology to bring together physicians and scientists to investigate common mechanisms across neurodegenerative disorders, and the Dark Matter Project at the Center for Synthetic Regulatory Genomics at NYU Langone Health.

A list of our previous funders can be found here.

WHO WE ARE

what we've done

SELECTED PUBLICATIONS

(The most up-to-date list is at Pubmed)

Prakash P, Erdjument-Bromage H, O'Dea MR, Munson CN, Labib D, Fossati V, Neubert TA, Liddelow SA (2023) Proteomic profiling of interferon-responsive reactive astrocytes in rodent and human. Glia 72(3):625-642. PMID: 38031883.

Frazel PW, Labib D, Fisher T, Brosh R, Pirjanian N, Marchildon A, Boeke JD, Fossati V, Liddelow SA (2023) Longitudinal scRNA-seq analysis in mouse and human informs optimization of rapid mouse astrocyte differentiation protocols. Nat Neurosci 26(10):1726-1738. PMID: 37697111.

Guttenplan KA, Weigel MK*, Prakash P*, Wijewardhane PR, Hasel P, Rufen-Blanchette U, Münch AE, Blum JA, Fine J, Neal MC, Bruce KD, Gitler AD, Chopra G, Liddelow SA, Barres BA (2021) Neurotoxic reactive astrocytes induce cell death via saturated lipids. Nature 599:102–107. PMID: 34616039.

Scientific and media coverage

Research highlight: Jamie Talan (2021) Reactive astrocytes and Alzheimer’s disease. J Alz Dis.

Research Highlight: Tom Fagan. ELOVL hurts—enzyme makes lipids that turn astrocytes toxic. AlzForum, October 7, 2021.

Media coverage: Shira Polan. Toxic fatty acids to blame for brain cell death after initial injury. NYU Langone Health October 6, 2021.

Data available online here (proteomic, lipidomic, and metabolomic datasets).

Hasel P, Rose IVL, Sadick JS, Kim RD, Liddelow SA (2021) Neuroinflammatory astrocyte subtypes in the mouse brain. Nat Neurosci 24:1475-1487. PMID: 34413515.

Scientific and media coverage

Research Highlight: High-res spatial transcriptomics offers new views of mouse brain. Alzforum, August, 2022.

Data available online here (bulk RNAseq and nanostring) and here (single cell and spatial data).

Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung W-S, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Dawson VL, Dawson TM, Buckwalter MS, Rowitch DH, Stevens B, Barres BA (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481-487. PMID: 28099414.

Scientific and media coverage

Research Highlight: Yates D (2017) A toxic reaction. Nat Rev Neurosci 18:130.

Research Highlight: Ridler C (2017) Microglia-induced reactive astrocytes – toxic players in neurological disease? Nat Rev Neurol 13:127.

Media Coverage: Pagan Kennedy. An Ancient Cure for Alzheimer’s? New York Times July 14, 2017.

Media Coverage: Carolyn Gregoire. Brain Cells of ‘Villainous Character’ Might Explain Diseases Like Parkinson’s. Huffington Post January 25, 2017.

join us

POSTDOCTORAL RESEARCHERS

Candidates with an excellent research record and an excitement for asking tough questions should email Shane with a brief introduction, CV, and the names and contact information of at least two references.

GRADUATE STUDENTS

Graduate students will need to apply to a Graduate Training program at NYU before joining the lab. More information on options for Graduate Training in Neuroscience at NYU can be found here.

wHere we are

We are a part of the Neuroscience Institute and affiliated with the Departments of Neuroscience & Physiology and Ophthalmology and the Parekh Center for Interdisciplinary Neurology @ NYU Grossman School of Medicine in New York City. 

Want to know more about the lab, or glia in general? Drop us a note - we'd love to hear from you.

liddelowlab@gmail.com