Lucas Cheadle

Lucas Martin Cheadle

Assistant Professor

Ph.D., Neuroscience, Yale University, 2014

cheadle@cshl.edu | 516-367-5920

Cheadle Lab Website   Faculty Profile

The trillions of connections between brain cells enable complex thought and behavior. These connections are wired with great precision through both genetics and in response to an organism’s experiences. Our lab seeks to understand how experiences engage specialized immune cells called microglia to shape the connectivity and function of the brain. We are further interested in how impairments in these processes can contribute to neurodevelopmental disorders such as autism.

The powerful influence of sensory experience on brain development has been appreciated since the 1960s. Yet, even today, the fundamental cellular and molecular mechanisms through which sensory input shapes developing neural circuits remain largely mysterious. The Cheadle lab recently discovered that sensory experience alters gene and protein expression in microglia, the resident immune cells of the brain. These sensory-induced changes allow microglia to interact with neighboring neurons to strengthen and maintain a subset of synaptic connections and to eliminate others. These findings raise the exciting possibility that microglia, which are predominantly associated with immune responses to injury and disease, also decode salient features of the physical world and contribute to neural responses to the environment.

The Cheadle lab applies a multidisciplinary approach to the visual system of the mouse to investigate the contributions of microglia to sensory experience-dependent synapse development and plasticity. They further seek to identify the molecular mechanisms through which microglia effect changes at synapses and thereby exert control over brain function. To accomplish this, the Cheadle lab images microglial interactions with synapses in the brains of living mice, which allows the researchers to characterize the specific features of the environment to which microglia respond. In parallel, the research team uses cutting-edge single-cell transcriptomic and genomic strategies, such as single-cell RNA-sequencing, to profile the molecular changes in microglia that are elicited by distinct sensory stimuli. With these combined approaches, the Cheadle lab is interrogating the ways in which environmental stimuli converge upon the microglial genome to shape neural circuit development and function.

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All Publications

The cytokine receptor Fn14 is a molecular brake on neuronal activity that mediates circadian function in vivo

2 Apr 2024 | bioRxiv
Ferro, Austin, Arshad, Anosha, Boyd, Leah, Stanley, Tess, Berisha, Adrian, Vrudhula, Uma, Gomez, Adrian, Borniger, Jeremy, Cheadle, Lucas

Integrated high-confidence and high-throughput approaches for quantifying synapse engulfment by oligodendrocyte precursor cells

25 Aug 2023 | bioRxiv
Kahng, Jessica, Xavier, Andre, Ferro, Austin, Auguste, Yohan, Cheadle, Lucas

Emerging roles of oligodendrocyte precursor cells in neural circuit development and remodeling

Aug 2023 | Trends in Neurosciences | 46(8):628-639
Buchanan, JoAnn, da Costa, Nuno, Cheadle, Lucas

Neuron-glia communication through bona fide synapses

5 May 2023 | Nature Reviews Neuroscience
Cheadle, Lucas

Publisher Correction: Oligodendrocyte precursor cells engulf synapses during circuit remodeling in mice.

Dec 2022 | Nature Neuroscience | 25(12):1735
Auguste, Yohan, Ferro, Austin, Kahng, Jessica, Xavier, Andre, Dixon, Jessica, Vrudhula, Uma, Nichitiu, Anne-Sarah, Rosado, Daniele, Wee, Tse-Luen, Pedmale, Ullas, Cheadle, Lucas

Oligodendrocyte precursor cells engulf synapses during circuit remodeling in mice

28 Sep 2022 | Nature Neuroscience
Auguste, Yohan, Ferro, Austin, Kahng, Jessica, Xavier, Andre, Dixon, Jessica, Vrudhula, Uma, Nichitiu, Anne-Sarah, Rosado, Daniele, Wee, Tse-Luen, Pedmale, Ullas, Cheadle, Lucas

When the levee of sympathetic outflow breaks

9 Aug 2022 | Immunity | 55(8):1334-1336
Ferro, Austin, Cheadle, Lucas

Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

2021 | Frontiers in Immunology | 12:703527
Ferro, Austin, Auguste, Yohan, Cheadle, Lucas

Sensory Experience Engages Microglia to Shape Neural Connectivity through a Non-Phagocytic Mechanism.

11 Nov 2020 | Neuron | 108(3):451-468.e9
Cheadle, Lucas, Rivera, Samuel, Phelps, Jasper, Ennis, Katelin, Stevens, Beth, Burkly, Linda, Lee, Wei-Chung, Greenberg, Michael

Sensory lesioning induces microglial synapse elimination via ADAM10 and fractalkine signaling

Jul 2019 | Nature Neuroscience | 22(7):1075-1088
Gunner, G, Cheadle, L, Johnson, K, Ayata, P, Badimon, A, Mondo, E, Nagy, M, Liu, L, Bemiller, S, Kim, K, Lira, S, Lamb, B, Tapper, A, Ransohoff, R, Greenberg, M, Schaefer, A, Schafer, D

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