Frederick Christian Bennett, M.D.

faculty photo
Assistant Professor of Psychiatry
Member, Translational Center of Excellence for Hematopoietic Stem Cell Engineering
Member, Institute for Immunology and Immune Health
Associate Member, Abramson Cancer Center
Department: Psychiatry

Contact information
3501 Civic Center
Rm 6026
Philadelphia, PA 19104
Office: 2157467275
Education:
B.S. (Biology, Magna cum Laude)
Haverford College, 2003.
M.D.
Stanford University School of Medicine, 2011.
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Description of Research Expertise

Research Interests: Role of microglia in brain health and disease

Keywords: microglia, glia, macrophages, inflammation, neuroinflammation

Research Summary: Our laboratory studies microglia, the brain’s resident immune cells. These mysterious cells play important roles in brain health and disease, but are poorly understood. We focus primarily on two related questions: 1) What are the environmental signals and intrinsic properties that govern microglial function? 2) How do these signals and properties contribute to brain health and disease? To answer these questions, we have developed tools to transplant microglia and other macrophages (including from humans) into the rodent brain, allowing dissection of environmental versus cell intrinsic factors controlling microglial function in health and disease. In parallel, we are adopting brain macrophage transplantation for therapeutic use.

Personal lab webpage: www.fcblab.org

Rotation Projects: We attempt to design rotation projects customized to the lab's current trajectory and student interest. Please feel welcome to contact Dr. Bennett by email to discuss current project opportunities.

Selected Publications

Schafer DP, Stevens B, Bennett ML, Bennett FC.: Role of Microglia in Central Nervous System Development and Plasticity. Cold Spring Harb Perspect Biol 17: a041810, Oct 2025.

O'Brien CA, Delcy SAS, Shukla S, Levitt EM, Cohen AS, Bennett ML, Bennett FC.: Neonatal microglia replacement in mice modulates seizure severity in adulthood. Mol Ther Aug 2025.

Ortega-Burgos Y, Dar AA, Tomishima SA, Guha I, Brien CO, Porter N, Bennett FC, Oliver PM.: Loss of Cullin 5 in myeloid cells protects against autoimmune neuroinflammation. Front Immunol 16: 1611818, Aug 2025.

Sukhina A, Queriault C, Roy S, Hall E, Rome K, Aggarwal M, Nunn E, Weiss A, Nguyen J, Bennett FC, Bailis W.: Malnutrition drives infection susceptibility and dysregulated myelopoiesis that persists after refeeding intervention. Elife 13: RP101670, Jul 2025.

Axsom J, Bennett FC.: A microglia identity crisis. Neuron 113: 1661-1663, Jun 2025.

Aisenberg WH, O'Brien CA, Sangster M, Yaqoob F, Zhang Y, Temsamrit B, Thom S, Gosse L, Chaluvadi S, Elfayomi B, Lee G, Polam V, Levitt EM, Liu G, Lombroso SI, Nemec KM, Clowry G, Nieves C, Rawat P, Church E, Martinez D, Shoffler C, Kancheva D, Petucci C, Taylor D, Kofler J, Erskine D, Movahedi K, Bennett ML, Bennett FC.: Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease. Immunity 58: 1254-1268, May 2025 Notes: Commentary: Trends Immunol. 2025 Jun;46(6):429-431. Press: www.alzforum.org/news/research-news/replacing-rogue-microglia-treats-monogenic-brain-disease-krabbe; www.chop.edu/news/preclinical-study-childrens-hospital-philadelphia-highlights-innovative-approach-replacing.

Nemec KM, Uy G, Chaluvadi VS, Purnell FS, Elfayoumi B, Byerly L, O'Reilly ML, O'Brien CA, Aisenberg WH, Lombroso SI, Guo X, Blank N, Oon CH, Yaqoob F, Temsamrit B, Rawat P, Thaiss CA, Bailis W, Williamson AP, Wang Q, Bennett ML, Bennett FC.: Microglia replacement by ER-Hoxb8 conditionally immortalized macrophages provides insight into Aicardi-Goutières Syndrome neuropathology. bioRxiv May 2025.

Bastos J, O'Brien C, Vara-Pérez M, Mampay M, van Olst L, Barry-Carroll L, Kancheva D, Leduc S, Lievens AL, Ali L, Vlasov V, Meysman L, Shakeri H, Roelandt R, Van Hove H, De Vlaminck K, Scheyltjens I, Yaqoob F, Lombroso SI, Breugelmans M, Faron G, Gomez-Nicola D, Gate D, Bennett FC, Movahedi K.: Monocytes can efficiently replace all brain macrophages and fetal liver monocytes can generate bona fide SALL1(+) microglia. Immunity 58: 1269-1288, May 2025 Notes: Commentary: Trends Immunol. 2025 Jun;46(6):429-431. Press: www.alzforum.org/news/research-news/replacing-rogue-microglia-treats-monogenic-brain-disease-krabbe; www.chop.edu/news/preclinical-study-childrens-hospital-philadelphia-highlights-innovative-approach-replacing

Bennett FC, Bennett ML.: Microglia cannibalism during neurodevelopment results in necroptotic cell death. PLoS Biol 22: e3002869, Oct 2024.

Profaci CP, Harvey SS, Bajc K, Zhang TZ, Jeffrey DA, Zhang AZ, Nemec KM, Davtyan H, O'Brien CA, McKinsey GL, Longworth A, McMullen TP, Capocchi JK, Gonzalez JG, Lawson DA, Arnold TD, Davalos D, Blurton-Jones M, Dabertrand F, Bennett FC, Daneman R.: Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism. Neuron 112: 2910-2921, Sep 2024.

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Last updated: 10/22/2025
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