Mariko BENNETT LAB
The Children’s Hospital of Philadelphia
University of Pennsylvania
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 method gene therapy and targeting. We are fascinated by the ability of microglia to restrict viral infection and are uncovering new microglial restriction factors and methods for targeting microglia with experimental viruses to introduce genes.
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.
The Mariko Bennett Lab
Mariko L Bennett MD, PhD
Principal Investigator
Asst Professor of Neurology & Pediatrics
Children’s Hospital of Philadelphia
University of Pennsylvania
Greg Salimando, PhD
Research Associate
Helen Moniz, BS
Research Technician
Brian Temsamrit, MSE
Laboratory Manager
Priyanka Rawat, PhD
Bioinformatician
Genevieve Uy, BS
Research Technician
Micaela O’Reilly, PhD
Post Doc
Asif A. Dar, PhD
Research Associate
Anna Foltz, BS
Research Technician
Graduate Students
Jordan McKinney, MS
University of Pennsylvania
Neuroscience Graduate Group
Madison Sangster, BS
University of Pennsylvania
Gene Therapy and Vaccine Program
Alex Martinez Lopez, MS
University of Pennsylvania
Neuroscience Graduate Group
Ryan Rahman, BS
University of Pennsylvania
Neuroscience Graduate Group & MSTP (Rotating Fall 2024)
Undergraduate Students
Hannah Gong
University of Pennsylvania .
Kwame Boateng
University of Pennsylvania
Katherine Andres
University of Pennsylvania.
Lab Alumni
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Cassaundra Nieves, Research Technician
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Cooper Penner, Perelman School of Medicine
Tavian Sanchez, University of Pennsylvania
Diana Abraham, University of Pennsylvania
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
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Lab News
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March 2024
Madison Sangster starts her graduate rotation with the lab!
April 2024
Alexandra Martinez Lopez starts her graduate rotation with the lab!
Greg Salimando and his team placed 2nd at the Asset Evaluation competition hosted by University of Pennsylvania Biotech Group.
Members of the lab participated in the University of Pennsylvania, MINS Year of Neuroimmunology Symposium!
May 2024
Hannah Gong starts her summer internship with the lab!
The Mariko Bennett Lab attends Gliadelphia's 2024 Spring Salon!
June 2024
Alexandra Martinez Lopez has committed as a graduate student to the Mariko Bennett Lab!
Anna Foltz joins the lab as a Research Techician.
Tavian Sanchez and Diana Abraham start their graduate rotation with the lab!
Dr. Mariko Bennett named to CHOP's Faculty Honor Roll for her commitment to resident education!
The Mariko Bennett Lab, the Chris Bennett Lab and the Shane Liddelow Lab participated in their annual lab retreat!
July 2024
Madison Sangster has committed as a graduate student to the Mariko Bennett Lab!
Micaela O'Reilly joins the lab as a Post Doc!
August 2024
The Mariko Bennett Lab attends the "Glia in Health and Disease" meeting at Cold Spring Harbor Laboratory.
MBL is award their first R01 to study Aicardi Goutieres Syndrome
Helen Moniz joins the lab as a Research Technician!
Hannah Gong receives the Rachleff Scholarship in undergraduate engineering to pursue research in the Mariko Bennett Lab!
Ryan Rahman starts his graduate rotation in the lab!
Katherine Andres and Kwame Boateng start their undergraduate research with the lab!
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July 2023
Mariko Bennett Lab opens!
August 2023
Gen Uy joins the lab as a research specialist!
Brian Temsamrit joins the lab as the lab manager!
September 2023
Greg Salimando joins the lab as a Post Doc!
The Mariko Bennet Lab participates in an invigorating Gliadelphia x ANA ancillary meeting with over 90 attendees, poster prizes, guest speakers, and PI flash presentations.
October 2023
Asif Dar joins the lab as a research associate!
Priyanka Rawat has joins the lab as a bioinformatician.
Mariko Bennett is a recipient of the NIH Director’s Early Independence Award! We love women in STEM! “Unlocking microglia targeting for neurotherapeutics”