The Movahedi Lab focuses on investigating the heterogeneity and functions of brain macrophages, aiming to understand their pivotal role in brain homeostasis and disease pathogenesis.
The Movahedi Lab focuses on investigating the heterogeneity and functions of brain macrophages, aiming to understand their pivotal role in brain homeostasis and disease pathogenesis.
Macrophages play an important role in maintaining brain tissue homeostasis. Brain macrophages are heterogeneous, exhibiting tissue-specific adaptations based on their location. Microglia are the macrophages found within the brain parenchyma, while border-associated macrophages (BAMs) reside in the brain’s border regions, such as the meninges, choroid plexus, and perivascular spaces. Our previous research has shown that BAMs are heterogeneous and transcriptionally distinct from microglia, underscoring the diversity of brain macrophages. Our current research aims to further delineate the identities and states of brain macrophages, identify the signals and gene regulatory networks driving their development and heterogeneity, and understand their role in maintaining brain homeostasis. We are also dedicated to understanding the role of macrophages in brain diseases, including primary brain cancer, neurodegenerative disorders like Alzheimer’s disease, and infectious brain diseases.”
Glioblastomas (GBM) are aggressive primary brain tumors that remain incurable, with a significant need for new treatment options. Most patients do not respond to cancer immunotherapy due to the immune-suppressive tumor microenvironment. GBM tumors are heavily infiltrated by macrophages, the predominant immune cells in the tumor, making them a key target for new therapeutic strategies. Our research aims to elucidate the origin, heterogeneity and functions of tumor-associated macrophages in GBM. We rely on single-cell and spatial omics profiling of human GBM tumors, supplemented with proof-of-concept studies in preclinical models. Our goal is to develop strategies for modulating macrophage functionality within tumors or to harness macrophages as vehicles for cell therapy, aiming to induce anti-tumor immunity.
Microglia are embryonically-derived cells that self-maintain throughout life and exhibit a striking self-renewal capacity. Therefore, these cells form an attractive target for cell therapy. Our goal is to pioneer new macrophage-based cell therapies for treating neurological disease. More specifically, we are developing strategies for replacing embryonic microglia with transplanted gene-engineered counterparts. This holds the potential to introduce a completely new treatment paradigm for a myriad of disorders, ranging from metabolic disease to neurodegeneration. Prof. Movahedi also received an ERC consolidator grant on this topic, which started in 2023.
Single-cell technologies have revolutionized biology and offer a powerful approach to study cellular heterogeneity. We have been early adopters of single-cell RNA sequencing, CITE-seq and high-dimensional flow cytometry, which we have used to study the brain immune landscape. We have also generated the brain immune atlas, a repository and tool for accessing and browsing of our single-cell datasets: www.brainimmuneatlas.org
Single-cell technologies have revolutionized biology and offer a powerful approach to study cellular heterogeneity. We have been early adopters of single-cell RNA sequencing, CITE-seq and high-dimensional flow cytometry, which we have used to study the brain immune landscape. We have also generated the brain immune atlas, a repository and tool for accessing and browsing of our single-cell datasets: www.brainimmuneatlas.org
Profiling cells in suspension offers a high-throughput approach for analyzing RNA and proteins at single-cell resolution. However, upon tissue dissociation, all spatial context is lost. Spatial information can offer insights into cell-cell interactions and the nature of the cellular niche and its microenvironmental cues. We are actively implementing high-dimensional spatial profiling methodologies and developing analysis pipelines for spatial profiling of the brain and tumor immune landscape. Additionally, we are complementing this with 2-photon intravital microscopy, to study brain macrophage dynamics in steady-state and disease.
Profiling cells in suspension offers a high-throughput approach for analyzing RNA and proteins at single-cell resolution. However, upon tissue dissociation, all spatial context is lost. Spatial information can offer insights into cell-cell interactions and the nature of the cellular niche and its microenvironmental cues. We are actively implementing high-dimensional spatial profiling methodologies and developing analysis pipelines for spatial profiling of the brain and tumor immune landscape. Additionally, we are complementing this with 2-photon intravital microscopy, to study brain macrophage dynamics in steady-state and disease.
We are adapting and optimizing protocols for the differentiation of human and mouse iPSCs towards myeloid progenitors that are able to develop into microglia and border-associated macrophages in the mouse brain. These methodologies are being used as a tool to study brain macrophage biology or as a therapeutic strategy for treating brain disease.
We are adapting and optimizing protocols for the differentiation of human and mouse iPSCs towards myeloid progenitors that are able to develop into microglia and border-associated macrophages in the mouse brain. These methodologies are being used as a tool to study brain macrophage biology or as a therapeutic strategy for treating brain disease.
We rely on gene targeting to develop new tools for tracking or modulating brain macrophages in vivo. Additionally, we are developing platforms for high-throughput CRISPR screening of microglia and macrophages in the context of brain homeostasis and disease.
We rely on gene targeting to develop new tools for tracking or modulating brain macrophages in vivo. Additionally, we are developing platforms for high-throughput CRISPR screening of microglia and macrophages in the context of brain homeostasis and disease.
