Aldh1l1eGFP confocal 080517_1.jpg
 

LIDDELOW LAB

Neuroscience institute @ NYU Langone

 

 

 

what we do

 Immunopanned rodent astrocyte grown in culture for 7 days. This astrocyte has been immunostained for the cytoskeletal protein GFAP (green). Image credit: Kevin Guttenplan, Stanford University

Immunopanned rodent astrocyte grown in culture for 7 days. This astrocyte has been immunostained for the cytoskeletal protein GFAP (green).
Image credit: Kevin Guttenplan, Stanford University

What do reactive astrocytes do?

Astrocytes are 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 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.

who we are

SHANE LIDDELOW, PRINCIPAL INVESTIGATOR

Shane gained his Bachelors of Science (Hons) and Biomedical Science from the University of Melbourne, Australia, majoring in Neuroscience and Anatomy & Cell Biology. He received his PhD with Norman Saunders in Pharmacology also from the University of Melbourne. His graduate work focused on the protective barriers of the brain during early development, specifically investigating ways to augment this system for delivery of drugs to the central nervous system.

As a postdoctoral fellow in the lab of Ben Barres at Stanford University his research focused on astrocytes, the major glial subtype in the brain. He discovered a close association between astrocytes, microglia (the resident immune cells of the brain), and abnormal neuron function. His most recent research showed that one form of reactive astrocyte is induced by factors released by microglia. These reactive astrocytes release a toxic factor that kills specific subtypes of neurons and are present in brains of patients with Alzheimer’s, Parkinson’s, Huntington’s disease, and Amyotrophic Lateral Sclerosis (Lou Gehrig’s disease), as well as in Multiple Sclerosis.

Shane was a recipient of the NHMRC (Australia) CJ Martin Training Award (2012-2016), the Glenn Foundation award for Aging in 2016, and was named a STATNews Wunderkind in 2017.

 liddelowlab@gmail.com

liddelowlab@gmail.com

what we've done

selected publications

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

Clarke LE, Liddelow SA, Chakraborty C, Münch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivityProc Natl Acad Sci USA 115(8):E1896-E1905. PMID: 29437957.

Data available online here

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) Activated microglia induce neurotoxic reactive astrocytes via Il-1α, TNFα, and C1q. Nature 541:481-487. PMID: 28099414.

Scientific and media coverage
Research Highlight: Burda JE, Sofroniew MV (2017) Seducing astrocytes to the dark side. Cell Res 27:726-727. 
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.

Shi Y, Yamada K, Liddelow SA, Smith ST, Zhao L, Luo W, Tsai R, Spina S, Grinberg L, Rojas J, Gallardo G, Wang K, Roh J, Robinson G, Finn MB, Jiang H, Sullivan P, Wood M, Baufeld C, Wood M, Sutphen C, McCue L, Xiong C, Del-Aguila J, Morris J, Cruchaga C, Fagan A, Miller B, Boxer B, Seeley W, Butovsky O, Barres B, Paul S, Holtzman D. ApoE4 markedly exacerbates tau-mediated neurodegeneration in a mouse model of tauopathyNature 549:523-527. PMID: 28959956.

Scientific and media coverage
Research Highlight: Underwood E (2017) How ApoE4 endangers brainsScience 357:1224.
Media coverage: Is this the Alzheimer’s gene? Daily Mail September 20, 2017.

Liddelow SA, Barres BA (2017) Reactive astrocytes: production, function, and therapeutic potential. Immunity 46(6):957-967. PMID: 28636962.

Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, Weissman IL, Chang EF, Li G, Grant GA, Hayden-Gephart M, Barres BA (2016) New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci USA 113(12):E1738-1746. PMID: 26884166.

Data available online here
Scientific and media coverage
Research Highlight: Segal BM, Giger RJ (2016) Stable marker for plastic microglia. PNAS 113:3130-3132.
 Astrocytes (magenta) and microglia (yellow) in the brain following an inflammatory insult.

Astrocytes (magenta) and microglia (yellow) in the brain following an inflammatory insult.

join us

We are seeking inquisitive, motivated, and fun people to help us investigate astrocytes in disease and following trauma. We have projects in neurodegeneration, trauma, and development.

 

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.

where we are

We are a part of the Neuroscience Institute and affiliated with the Department of Neuroscience and Physiology @ NYU Langone 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