CHRIS BENNETT

LAB

University of Pennsylvania

The Children’s Hospital of Philadelphia

WE’RE HIRING! EXPLORE OPPORTUNITIES HERE

Research Questions

Microglia are the brain’s resident immune cells. They have specialized functions, intriguing developmental origins, and a remarkable ability to rapidly populate the brain. They are both similar and different from blood-derived macrophages, and those resident in other tissues. To more deeply understand what microglia do, we focus on three central questions:

What is microglial identity?

Microglia are highly specialized tissue macrophages. We are interested in identifying the external signals and intrinsic properties responsible for the unique attributes of microglia.

How to replace microglia?

We are developing methods to deplete microglia and replace them with transplanted surrogates that can be engineered to treat disease. Refining these methods requires improved understanding of how macrophages enter and colonize the brain.

How do microglia contribute to health and disease?

We use macrophage transplantation to understand how microglia are involved in brain disease, and how to leverage them for treatment.

This Year’s news

March

Esteban was awarded the Next Generation Research Grant in Lewy Body Diseases by the Alzheimer's Association and American Brain Foundation
Kelsey’s paper was featured in an eLife editorial

November 2025
- Sonia’s paper was published in Molecular Therapy‍ ‍
September 2025
- Sai was awarded an Rosenau Family Research Foundation grant
- Esteban was awarded a Lewy Body Dementia Association mentorship award
August 2025
- Carleigh’s paper was published in Molecular Therapy
July 2025
- Yohaniz defended her PhD! Congrats Dr. Ortega!
June 2025
- Kelsey’s final version of record paper is published at eLife
- Will’s paper was featured on alzforum
- Daniel Shapiro passed his candidacy exam!
- Taylor Phillips-Jones passed her candidacy exam!
May 2025
- Ryan Anderson passed his candidacy exam!
- Will was awarded the Alavi-Dabiri Postdoctoral Research Fellowship Award
- Will’s paper was selected for the CHOP Klaus Hummeler High Impact Publication Award
April 2025
- Our paper studying the therapeutic and pathologic role of macrophages in Krabbe disease is published in Immunity
- Vidhur won the Eliot Stellar Award for his outstanding honors thesis presented at the undergrad. neuroscience student research symposium
March 2025
- Chris is named the recipient of the 1907 Foundation Trail Blazer award
February 2025
- Jessie Axsom joined the lab!
January 2025
- Sonia defended her thesis and is now officially Dr. Lombroso!
October 2024
- Taylor Phillips-Jones joined the lab!
September 2024
- Kelsey Nemec successfully defended her PhD!
- Sonia presented her thesis work at the PGG annual retreat, and won an award for her talk
- Sonia was selected to give a talk at the Gliadelphia Fall Symposium
- Will gave a flash talk and won the postdoctoral poster award at the Gliadelphia Fall Symposium
- Daniel Shapiro joined the lab!
August 2024
- Lab attends Cold Spring Harbor Glia in Health and Disease meeting - Chris co-chairs the session on modeling human glia
July 2024
- Eli Levitt joins the lab as a Research Specialist - Welcome, Eli!
June 2024
- Ryan Anderson (PGG Graduate Student) officially joins the Bennett Lab to complete his thesis work! Welcome back, Ryan!
May 2024
- Mara Davis (GTV Graduate Student) successfully completes her Qualifying Exam and becomes an official PhD Candidate! Huge congratulations, Mara!
- Chris wins the 2024 CHOP Award for Excellence in Mentoring Research Trainees! Various lab members wrote essays on why Chris was so deserving of the award, and CHOP Research agreed! Congrats, Chris! Everyone is so grateful to have you as a mentor!
- Will Aisenberg (Postdoctoral Fellow) and Kelsey Nemec (NGG Graduate Student) present posters at the 2024 Children’s Hospital of Philadelphia Research Symposium - and BOTH win Poster Prizes!
April 2024
- Esteban Luna (Resident Physician) presents a poster at the American Academy of Neurology (AAN) Annual Meeting in Denver, CO!
- Graduate Students Kelsey Nemec (NGG), Sonia Lombroso (PGG), Sai Chaluvadi (NGG/MSTP), and Mara Davis (GTV) present posters at the MINS Year of Immunology Symposium - and Sonia win’s the Poster Prize! Great work, all!
March 2024
- Sai Chaluvadi (NGG/MSTP Student) gives an invited speaker talk at the annual Krabbe Translational Research Network (KTRN) Meeting in Minnesota. Way to go, Sai!
- Jenny Smith (BioE) joins the lab as a Rotation Student!
January 2024
- Esteban Luna (Resident) and Ryan Anderson (PGG Rotation Student) join the lab! Welcome!
- The Bennett Lab celebrates its 5 year “labaversary”! Congrats, Chris and co. - here’s to many more!

PUBLICATIONS

Microglia replacement by peripheral delivery of CSF1R inhibitor-resistant hematopoietic cells

Molecular Therapy | https://doi.org/10.1016/j.ymthe.2025.10.050

Neonatal microglia replacement in mice modulates seizure severity in adulthood

Molecular Therapy | https://doi.org/10.1016/j.ymthe.2025.08.039

Direct microglia replacement reveals pathologic and therapeutic contributions of brain macrophages to a monogenic neurological disease

Immunity 2025 | 10.1016/j.immuni.2025.03.019

Microglia replacement by ER-Hoxb8 conditionally immortalized macrophages provides insight into Aicardi-Goutières Syndrome neuropathology

Elife 2024 | https://doi.org/10.7554/eLife.102900.1

Molecular and metaboic heterogeneity of astrocytes and microglia

Cell Metabolism 2023 | DOI: 10.1016/j.cmet.2023.03.006

Engineering an inhibitor-resistant human CSF1R variant for microglia replacement

Journal of Experimental Medicine 2023 | DOI: 10.1084/jem.20220857

Microglia in antiviral immunity of the brain and spinal cord

Seminars in Immunology 2022 | DOI: 10.1016/j.smim.2022.101650

Treatment of a genetic brain disease by CNS-wide microglia replacement

Science Translational Medicine 2022 | DOI: 10.1126/scitranslmed.abl9945

The influence of environment and origin on brain resident macrophages and implications for therapy

Nature Neuroscience 2019 | DOI: 10.1038/s41593-019-0545-6

A Combination of Ontogeny and CNS Environment Establishes Microglial Identity

Neuron 2018 | DOI: 10.1016/j.neuron.2018.05.014

Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures

Neuron 2017 | DOI: 10.1016/j.neuron.2017.04.043

Neurotoxic reactive astrocytes are induced by activated microglia

Nature 2017 | DOI: 10.1038/nature21029

New tools for studying microglia in the mouse and human CNS

Proceedings of the National Academy of Sciences of the United States of America 2016 | DOI: 10.1073/pnas.1525528113

Isolation and Culture of Microglia

Current Protocols in Immunology 2018 | DOI: 10.1002/cpim .7 0

Full publication list for Dr. Bennett: orcid.org/0000-0003-2570-0620

Biosketch

PEOPLE

Research Question: How can we treat diseases using microglia?Hobbies: pep talks, parenting, brewing, wandering around — Frederick “Chris” Bennett, MD
Principal Investigator
Research Question: How can we treat diseases using microglia?
Hobbies: pep talks, parenting, brewing, wandering around

Esteban Luna, MD, PhD
Resident Physician
Research Question: How does microglial dysfunction contribute to Parkinson’s Disease?
Hobbies: spending time with family and friends, exercising, reading

Research Question: Are microglia and macrophages functionally different?Hobbies: volleyball, horror movies, not exercising — Carleigh O’Brien, PhD
Postdoctoral Fellow
Research Question: Are microglia and macrophages functionally different?
Hobbies: volleyball, horror movies, not exercising

Research Question: Can replacing diseased microglia with healthy surrogates improve neurological disease outcomes?Hobbies: hiking, restaurant hopping, cocktail making, baking, parenting — Will Aisenberg, PhD
Postdoctoral Fellow
Research Question: Can replacing diseased microglia with healthy surrogates improve neurological disease outcomes?
Hobbies: hiking, restaurant hopping, cocktail making, baking, parenting

Krystal Oon, PhD
Postdoctoral Fellow
Research Question: Can engineered macrophages be used to treat neurodegenerative diseases?
Hobbies: yoga, meditation, ice skating, collecting plants

Jessie Axsom, PhD
Postdoctoral Fellow
Research question: How do microglia regulate metabolism, and how does metabolism regulate microglia?
Hobbies: Running, reading, watching WNCAA sports, and spoiling my cats

Research question: Can we treat neurological diseases by replacing bad microglia with good microglia? Hobbies:  movies, reading, driving — Fazeela Yaqoob, MS
Research Associate
Research question: Can we treat neurological diseases by replacing bad microglia with good microglia?
Hobbies: movies, reading, driving

Research Question: How can we replace diseased microglia with healthy surrogates?Hobbies: playing/watching sports (basketball, football, volleyball, frisbee), watching light-hearted TV shows, trying new restaurants, hanging out with friends — Sai Chaluvadi, BS
Graduate Student (NGG, MSTP)
Research Question: How can we replace diseased microglia with healthy surrogates?
Hobbies: playing/watching sports (basketball, football, volleyball, frisbee), watching light-hearted TV shows, trying new restaurants, hanging out with friends

Ryan Anderson, BS
Graduate Student (PGG)
Research Question: How can we use hematopoietic stem cells to study and treat neurodegenerative disease?
Hobbies: music (making it, collecting it, teaching it), soccer, basketball, running, hiking, being a cat dad

Daniel Shapiro, BS
Graduate Student (GTV, MSTP)
Research Question: Do microglia retain a memory of infection?
Hobbies: bar hopping, being with friends, trying new restaurants, paint by numbers, playing guitar poorly

Taylor Phillips-Jones, BS
Graduate Student (NGG, MSTP)
Research Question: How do prenatal insults alter microglial function in the developing brain?
Hobbies: baking, painting, trying new restaurants

Eli Levitt, BA
Research Assistant
Hobbies: knitting, quilting, ultimate frisbee, fermentation

Vishal Kanigicherla, BS, BA
Research Assistant
Hobbies: Any games (chess, poker, video games, word games), finding new dishes to cook, reading, academic trivia

Bilal Elfayoumi
Undergraduate Student
Hobbies: playing percussion, watching movies, hanging with friends, baking/eating too many sweets

LAB ALUM

Gavin Lee (undergraduate student 2022-2025) - Clinical research coordinator @ Penn
Vidhur Polam (undergraduate student 2022-2025) - Research assistant in orthopedic surgery private practice
Gary Liu, MD, PhD (Resident Physician 2023-2025) - Private Practice
Yohaniz Ortega, PhD (Graduate Student 2020-2025) - Consulting
Emily Church (Research Assistant 2023-2025) - Masters in Public Health @ UW
Sonia Lombroso, PhD (Graduate Student 2020-2025) - Postdoc @ UCSF
Kelsey Nemec, PhD (Graduate Student, 2019-2024) - Postdoc @ Seattle Children’s Hospital
Freddy Purnell (Research Associate, 2021-2023) - PhD Student @ Penn
Matias Porras Paniagua, PhD (Graduate Student, 2019-2023) - Associate @ Insight Partners
Dave Marzan, PhD (Postdoctoral Fellow, 2019-2021) - Lecturer @ The College of New Jersey
Ethan Abraham (Undergraduate Researcher, 2020-2021) - Undergraduate Student @ Penn
Graham Peet (Research Specialist, 2019-2021) - PhD Student @ UC-Denver