Lucas Martin Cheadle
Assistant Professor
Ph.D., Neuroscience, Yale University, 2014
cheadle@cshl.edu | 516-367-5920
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.
Lucas Cheadle named a 2022 NIH Director’s New Innovator
October 4, 2022
Cheadle is CSHL’s first recipient of the NIH Director’s New Innovator Award. It supports his new work on inflammation and autism spectrum disorders.
The unexpected cells helping to shape young brains
September 28, 2022
CSHL scientists discover cells called OPCs help shape developing brains by eliminating unnecessary connections.
CSHL neuroscientist Lucas Cheadle named Emerging Scholar
January 20, 2022
Diverse: Issues In Higher Education magazine named CSHL Assistant Professor Lucas Cheadle a top “40 and under” scholar.
CSHL’s Lucas Cheadle receives Rita Allen Award
July 26, 2021
CSHL Assistant Professor Lucas Cheadle received the Rita Allen Scholar Award from the Rita Allen Foundation.
CSHL neuroscientist awarded Klingenstein-Simons Fellowship
June 10, 2021
Assistant Professor Lucas Cheadle was awarded the Klingenstein-Simons Neuroscience Fellowship for his microglia research.
CSHL neuroscientist Lucas Cheadle named McKnight Scholar
June 4, 2021
Assistant Professor Lucas Cheadle has been named a 2021 McKnight Scholar for his work on microglia.
Cold Spring Harbor Laboratory: Science is hope
December 21, 2020
The Laboratory is a leading research center for genetics, cancer, plant biology, quantitative biology, and neuroscience.
Assistant Professor Cheadle named Next Generation Leader
November 19, 2020
CSHL Assistant Professor Lucas Cheadle has been named a Next Generation Leader by the Allen Institute for Brain Science.
Immune cells sculpt circuits in the brain
September 14, 2020
Immune cells play an unexpected role in fine-tuning the brain’s neural circuits.
How the senses shape the brain
August 6, 2020
Neuroscientist Lucas Cheadle joins CSHL neuroscience faculty, and studies how outside stimuli affect brain development.
All Publications
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
Visual Experience-Dependent Expression of Fn14 Is Required for Retinogeniculate Refinement
8 Aug 2018 | Neuron | 99(3):525-539.e10
Cheadle, L, Tzeng, C, Kalish, B, Harmin, D, Rivera, S, Ling, E, Nagy, M, Hrvatin, S, Hu, L, Stroud, H, Burkly, L, Chen, C, Greenberg, M
Publisher Correction: Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex.
Jul 2018 | Nature Neuroscience | 21(7):1017
Hrvatin, Sinisa, Hochbaum, Daniel, Nagy, M, Cicconet, Marcelo, Robertson, Keiramarie, Cheadle, Lucas, Zilionis, Rapolas, Ratner, Alex, Borges-Monroy, Rebeca, Klein, Allon, Sabatini, Bernardo, Greenberg, Michael
Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement
30 Jan 2018 | Proceedings of the National Academy of Sciences of USA | 115(5):E1051-E1060
Kalish, B, Cheadle, L, Hrvatin, S, Nagy, M, Rivera, S, Crow, M, Gillis, J, Kirchner, R, Greenberg, M
Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex
Jan 2018 | Nature Neuroscience | 21(1):120-129
Hrvatin, S, Hochbaum, D, Nagy, M, Cicconet, M, Robertson, K, Cheadle, L, Zilionis, R, Ratner, A, Borges-Monroy, R, Klein, A, Sabatini, B, Greenberg, M