Massachusetts General Hospital | Harvard Medical School
Microglia are the principal immune cells of the brain and are highly dynamic sentinels of the central nervous system. They survey tissue, sense injury, microbes, and disease-associated signals, and can shift between protective and pathogenic roles depending on context. We think about these responses through three essential microglial functions: sentinel, warrior, and nurturer. This site is meant to introduce those ideas through the work and questions that shape our lab.
Principal Investigator
Principal Investigator, Center for Immunology and Inflammatory Diseases, MGH
Physician, Infectious Disease Unit, MGH
Associate Professor of Medicine, Harvard Medical School
Dr. El Khoury directs a research program focused on microglia, macrophages, and innate immune recognition in neurologic and inflammatory disease. His lab's work bridges mechanistic immunology with clinical questions in neurodegeneration, glioma, and infection, with the goal of understanding how immune sensing pathways can be defined, measured, and ultimately redirected.
Research Interests
In disease states like glioblastoma, these intrinsic functions become dysregulated and ultimately enable tumor growth.
We study the core biology of microglia as sentinel, warrior, and nurturer cells that sense their environment, defend tissue, and maintain homeostasis. This includes our foundational work defining the microglial sensome and our continued interest in how microglial states are measured and interpreted.
Microglia in Alzheimer's disease cluster at sites of beta-amyloid deposition, attempting to clear beta-amyloid.
We study how microglial sensing, housekeeping, and defense functions become dysregulated across neurodegenerative disease, including Alzheimer's disease, and how that imbalance contributes to pathology. This includes long-standing work on beta-amyloid, scavenger receptors, and downstream innate immune signaling.
Microglial and immune responses after traumatic brain injury evolve over time and across brain compartments.
We study how microglial states change after traumatic brain injury, from early inflammatory signaling to longer-lived transcriptional programs that shape tissue repair, degeneration, and chronic neurological outcomes.
Microglia (red) phagocytosing a glioma cell (blue).
We showed that glioblastoma can hijack microglial gene expression, suppress tumor sensing and killing programs, and promote a microenvironment favorable for invasion and tumor propagation.
CMV reshapes monocyte signaling and gene-expression programs tied to viral sensing, inflammation, and phagocytosis.
We study innate immune responses to infectious pathogens and their overlap with inflammatory disease biology, including fungal pathogenesis, host-defense receptors such as CD36 and SCARF1, and CMV-driven immune reprogramming in transplantation.
Work focused on how microglia sense, defend, and maintain the brain across changing environments and disease states.
We identified a quantitative transcriptomic signature for microglia and defined the sensome as a set of genes encoding the machinery used to sense endogenous ligands and microbes. We also showed that aging shifts this sensing landscape, with reduced endogenous-ligand recognition and increased host-defense and microbial sensing programs.
Work examining how the sentinel, warrior, and nurturer functions of microglia become imbalanced in Alzheimer's disease and related neurodegenerative settings.
We reframed microglia through three linked functions: sensing, housekeeping, and protection against injurious self and non-self stimuli. This work positions Alzheimer's disease and related neurodegenerative disorders as diseases in which those functions become imbalanced, making microglial pathways potential therapeutic checkpoints.
Frontiers in Immunology, 2019
We showed that partial reduction of CX3CR1 was associated with lower amyloid burden, improved cognition, and restoration of neuronal beta-amyloid-degrading pathways in an Alzheimer's-like mouse model, highlighting a tractable microglial signaling axis with therapeutic implications.
Work focused on how microglia and broader neuroimmune programs evolve over time after traumatic injury.
Frontiers in Cellular Neuroscience, 2019
We mapped how microglial transcriptional programs change over time after traumatic brain injury, showing that the response is dynamic rather than fixed and that distinct phases of activation emerge as injury evolves.
We argued for a more time-resolved and disease-specific view of post-traumatic neuroinflammation, moving beyond oversimplified activation labels and toward transcriptomic and proteomic definitions of immune state.
Work defining how glioblastoma reshapes microglial behavior into sleepy, exhausted, and tumor-enabling states within the tumor microenvironment.
Journal of Neuroinflammation, 2020
We found that microglia interacting with tumor-derived extracellular vesicles showed downregulation of genes involved in sensing tumor cells, sensing danger signals, and tumor killing, alongside upregulation of programs associated with tumor spread. Similar signatures were observed in human glioblastoma datasets.
Work spanning innate pathogen recognition, fungal host defense, and immune reprogramming during transplantation.
Journal of Experimental Medicine, 2009
We helped define an evolutionarily conserved fungal sensing pathway in which the scavenger receptors SCARF1 and CD36 contribute to pathogen recognition, phagocytosis, and innate immune activation.
We showed that CMV-infected monocytes displayed impaired phagocytosis of fungal pathogens together with reduced expression of fungal recognition receptors, while simultaneously upregulating antiviral, pro-inflammatory chemokine, and inflammasome pathways linked to allograft dysfunction and graft-versus-host disease.
Future Directions
People
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Senior Research Technologist
Research Technician
Contact
Interested in joining us? Students, postdocs, or other research staff can reach out to Dr. El Khoury at jelkhoury@mgh.harvard.edu with a short note about themselves, their interest in the lab, and a resume/CV.
149 13th Street
Bay 6114
Charlestown, MA 02129
El Khoury Lab | Massachusetts General Hospital | Harvard Medical School
Website created by Daniel Schmidlin.