Mariko BENNETT LAB
The Children’s Hospital of Philadelphia
Welcome!
Research Questions
Microglia are the dynamic, resident parenchymal macrophages of the brain and spinal cord. They are powerful immune effectors and are distinct from other macrophages in our body and at brain borders. Our lab aims to develop new understandings of microglial function in health and disease, to realize their potential as the next generation of therapeutics for pediatric neuroimmunological disease
What do glia do in health and disease?
We study human tissues and disease models to understand the role of microglia and astrocytes in human neuroinflammatory disease. We also investigate how microglia help build the developing nervous system to identify new potential therapeutic approaches.
How can we better engineer microglia?
Viral transduction is a powerful gene therapy and targeting method. We are fascinated by how microglia limit viral infection and are uncovering new restriction factors. We are using this knowledge to develop new methods to target microglia with
When & how should we intervene?
Informed by Dr Bennett's clinical work, we are developing more robust disease models that more faithfully recapitulate human disease to know how and when intervention is necessary in the disease process.
Through all of this, we continue to develop a suite of shareable techniques & tools to allow others to make new and exciting discoveries about the function and dysfunction of microglia.
OUR Team
Mariko L Bennett MD, PhD
Principal Investigator
Asst Professor of Neurology & Pediatrics
Children’s Hospital of Philadelphia
University of Pennsylvania
Cassaundra Nieves
Research Specialist
Brian Temsamrit
Laboratory Manager
Greg Salimando, PhD
Research Associate
Genevieve Uy
Research Specialist
Priyanka Rawat, PhD
Bioinformatician
Asif A. Dar, PhD
Research Associate
Publications
(Click titles for full text PDF)
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Chadarevian JP, Lombroso SI, Peet GC, Hasselmann J, Tu C, Marzan DE, Capocchi J, Purnell F, Nemec K, Lahian A, Escobar A, England W, Caluvadi S, O’Brien C, Yaqoob F, Aisenberg W, Porras Paniagua M, Bennett ML, Spitale R, Davtyan H, Blurton-Jones M, Bennett FC. (2023). Engineering an inhibitor-resistant human CSF1R variant for microglia replacement. Journal of Experimental Medicine, 220(3), e20220857.
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Catenaccio E, Bennett ML, Massey S, Abend NS, Bergqvist C. (2022). Tonic Seizures in a Patient With Lennox–Gastaut Syndrome Manifest as “Icicles” Rather Than “Flames” on Quantitative EEG Analysis. Journal of Clinical Neurophysiology, 10-1097.
Su Y, Zhou Y, Bennett ML, Li S, Carceles-Cordon M, Lu L, Huh S, Jimenez-Cyrus D, Gu X, Kleinman JE, Hyde TM, Weinberger DR, Nauen DW, Song H, Ming G. (2022). A single-cell transcriptome atlas of glial diversity in the human hippocampus across the postnatal lifespan. Cell stem cell, 29(11), 1594-1610
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Yao M, Ventura PB, Jian Y, Rodriguez FJ, Wang L, Perry JSA, Yang Y, Wahl K, Crittenden RB, Bennett ML, Qi L, Gong C, Li X, Barres BA, Bender TP, Ravichandran KS, Janes KA, Eberhart CG, Zong H. (2020). Astrocytic trans-differentiation completes a multicellular paracrine feedback loop required for medulloblastoma tumor growth. Cell, 180(3), 502-520.
Bennett, Mariko L., and F. Chris Bennett. "The influence of environment and origin on brain resident macrophages and implications for therapy." Nature neuroscience 23.2 (2020): 157-166.
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Li Q, Cheng Z, Zhou L, Darmanis S, Neff NF, Okamoto J, Gulati G, Bennett ML, Sun LO, Clarke LE, Marschallinger J, Yu G, Quake SR, Wyss-Coray T, Barres BA. (2019). Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron, 101(2), 207-223.
Hutter G*, Theruvath J*, Graef CM*, Zhang M, Schoen MK, Manz EM, Bennett ML, Olson A, Azad TD, Sinha R, Chan C, Assad Kahn S, Gholamin S, Wilson C, Grant G, He J, Weissman IL, Mitra SS, Cheshier SH. (2019). Microglia are effector cells of CD47-SIRPα antiphagocytic axis disruption against glioblastoma. Proceedings of the National Academy of Sciences, 116(3), 997-1006.
Bohlen CJ, Bennett FC, Bennett ML. (2019). Isolation and culture of microglia. Current protocols in immunology, 125(1), e70.)
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Bennett FC, Bennett ML, Yaqoob F, Mulinyawe SB, Grant GA, Hayden Gephart M, Plowey ED, Barres BA. (2018). A combination of ontogeny and CNS environment establishes microglial identity. Neuron, 98(6), 1170-1183.
Rodda LB, Lu E, Bennett ML, Sokol CL, Wang X, Luther S, Barres BA, Luster AD, Ye CJ, Cyster JG. (2018). Single-cell RNA sequencing of lymph node stromal cells reveals niche-associated heterogeneity. Immunity, 48(5), 1014-1028.
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Valdearcos M, Douglass JD, Roblee MM, Dorfman MD, Stifler DR, Bennett ML, Gerritse I, Fasnacht RD, Barres BA, Thaler JP, Koliwad SK. (2017). Microglial inflammatory signaling orchestrates the hypothalamic immune response to dietary excess and mediates obesity susceptibility. Cell metabolism, 26(1), 185-197.
Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L, Bennett ML, Münch AE, Chung W, Peterson TC, Wilton DK, Frouin A, Napier BA, Panicker N, Kumar M, Buckwalter MS, Rowitch DH, Dawson VL, Dawson TM, Stevens B, Barres BA. (2017). Neurotoxic reactive astrocytes are induced by activated microglia. Nature, 541(7638), 481-487.
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Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Adil A, Tucker A, Weissman IL, Chang EF, Li G, Grant GA, Hayden Gephart MG, Barres BA. (2016). New tools for studying microglia in the mouse and human CNS. Proceedings of the National Academy of Sciences, 113(12), E1738-E1746.
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Zhang Y, Chen K, Sloan S, Bennett ML, Scholze AR, O’Keefe S, Phatnani H, Guarnieri P, Caneda C, Ruderisch N, Den S, Liddelow S, Zhang C, Daneman R, Maniatis T, Barres BA, Wu J. (2014). An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. Journal of Neuroscience, 34(36), 11929-11947.
Allen NJ, Bennett ML, Foo LC, Chakraborty C, Smith SJ, Barres BA. (2012). Astrocyte glypicans 4 and 6 promote formation of excitatory synapses via GluA1 AMPA receptors. Nature, 486(7403), 410-414.
Lorber B, Howe ML, Benowitz LI, Irwin N. (2009). Mst3b, an Ste20-like kinase, regulates axon regeneration in mature CNS and PNS pathways. Nature neuroscience, 12(11), 1407-1414.
Brenhouse HC, Howe ML, Stellar JR. (2007). Differential activation of cAMP response element binding protein in discrete nucleus accumbens subregions during early and late cocaine sensitization. Behavioral neuroscience, 121(1), 212.
Howe ML, Mehmud ZF, Saha S, Buratovich M, Stutius EA, Schmidt HD, Lenon AL, Reddicks C, Ivanov GS, Przyborski SA, Ozer JS. (2006). Transcription Factor IIA τ Is Associated with Undifferentiated Cells and Its Gene Expression Is Repressed in Primary Neurons at the Chromatin Level In Vivo. Stem Cells and Development, 15(2), 175-190.
Contact THe Lab
We have positions available for postdoctoral fellows, graduate students, and research assistants. Please inquire for more details!
Read more about opportunities in our lab here.
(Do NOT use this form to transmit patient information or for clinical inquiries. See “Links” page for clinical contacts)
Current Lab News
July 1
Mariko Bennett Lab opens!
August 1
Gen Uy joins the lab as a research specialist!
August 7
Brian Temsamrit joins the lab as lab manager!
SEPTember 12
MBLab participates in an invigorating Gliadelphia x ANA ancillary meeting with over 90 attendees, poster prizes, guest speakers, and PI flash presentations. See pictures below.
October 2
Asif Dar joins the lab as a research associate!
October 3
Mariko Bennett is a recipient of the NIH Director’s Early Independence Award! We love women in STEM! “Unlocking microglia targeting for neurotherapeutics”
