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LIDDELOW LAB

Neuroscience institute @ NYU Langone

 

 

 

WHAT WE DO

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.

 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

who we are

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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 Katarzyna Dziegielewska and 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.

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JESSICA SADICK, Postdoctoral Fellow

Jessica received her Bachelors of Arts in Botany (Summa Cum Laude with honors and distinction) from Connecticut College. As a post-baccalaureate, she worked at the MassGeneral Institute for Neurodegeneration maintaining induced pluripotent stem cells for Parkinson’s disease research and then at Correlagen Diagnostics analyzing patient sequencing data. Returning to academia, Jessica pursued and completed her PhD in Biotechnology from Brown University. Her graduate work focused on developing novel methods to enrich for cell subpopulations and to subsequently characterize their respective protein expression. She ultimately applied these techniques to the study of Alzheimer’s disease (AD) by generating protein signatures for neural cell types in AD primary tissue to further elucidate the role of cellular heterogeneity in AD etiology.

As a postdoctoral fellow, Jessica is interested in studying the role of reactive astrocytes in neurodegenerative disease. She aims to generate reactive astrocyte-specific -omic data as a means to identify novel therapeutic targets to alleviate, and ideally reverse, neurodegenerative damage.

Jessica was named a Connecticut College Winthrop Scholar (2010) and was a recipient of the NSF Graduate Research Fellowship in Neuroscience (2014-2017).

Read some of Jessica's work in Scientific Reports here.

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ALICE KWON, Graduate Student

Alice graduated from the University of California, Davis with a Bachelor of Science in Cell Biology.  She received a Dean’s Research Award for her undergraduate research on molecular interactions between the cell membrane and a membrane protein crucial to asymmetric embryonic cell division in C. elegans.  As a research technician at Caltech she studied host-microbe interactions using gnotobiotic mice.  She helped investigate a novel role for autophagy in host immune cells that recognize beneficial bacteria and prevent colitis.  

As a graduate student, she is interested in how the nervous and immune systems interact to maintain homeostasis.  She aims to study the role of astrocyte-like glial cells in the intestinal tract.

Read some of Alice's work in Science here.

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INDIGO ROSE, RESEARCH ASSOCIATE

Indigo graduated from Johns Hopkins University with a combined Bachelor and Master of Science in Neuroscience (Honors), with an additional major in Cognitive Science. As an undergraduate, he performed neuropathological analysis on postmortem human brain specimens at the Lieber Institute for Brain Development. He received the Emily and Thomas Meren Award for his work as a BS/MS student, researching the biology of extracellular vesicles in neuroimmune homeostasis, with applications to immune dysregulation in neuropsychiatric disorders. He helped investigate cytokine regulation in neuroinflammatory astrocytes by proteins such as glutathione S-transferase mu 1. Additionally, he helped discover the involvement of interleukin-33 in social and anxiety-like behaviors in mice.

In the Liddelow Lab, Indigo is investigating the biology of astrocytes and how they respond to injury and disease.

Read some of Indigo’s work in eNeuro here.

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.

were 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