at Emory University
HUMAN • GLIA • NEURODEVELOPMENT• STEM CELLS
Studying human glia with functional brain models
Glia are the most abundant cell types in the mammalian nervous system. They are integral to normal brain physiology, yet we still understand very little about how they develop, what functions they perform, and how they are involved in disease. We understand even less about these cells in humans because of the lack of direct access to intact, functioning human brain tissue.
Our lab is using pluripotent stem cells (iPSCs) derived non-invasively from skin samples to generate brain cells in the lab. Because the brain is a 3D structure and studying cells growing on a plate doesn't recapitulate its complexity, we are using human iPSCs to generate functional 3D structures that are patterned to mirror specific regions of the human brain. We can culture these 'brains-in-a-dish' for long periods of time to ask how normal brain development is occurring in a human system.
We are pursuing two big picture topics. First, how do human glia develop and what makes them unique? Secondly, given that glia play critical roles in helping neural circuit development, does abnormal glial development contribute to neurodevelopmental disorders like autism and schizophrenia? To answer these questions, we are using state-of-the-art genome engineering, stem cell biology, imaging, and neurobiological approaches. Our hope is that by investigating the potential contribution of this previously overlooked group of cells in the nervous system, we may be able to decipher new mechanisms and therapeutic targets to advance human health.
Dr. Steven Sloan is an Assistant Professor in the Department of Human Genetics, at the Emory University School of Medicine. He was born in Phoenix, Arizona and spent the latter half of his childhood in South Florida. For his undergraduate degrees in Biomedical Engineering and Biochemistry he attended the University of Miami, FL.
Steven received his MD and PhD degrees at Stanford University in the laboratory of Ben Barres, where he became fascinated with glia--the understudied and mysterious cell types that adjoin neurons within the nervous system. Given his interests in human medicine, Steven spent his PhD investigating the functions of human astrocytes. Along with his colleagues, he developed techniques to purify and profile each of the major CNS cell types from the rodent and human brain and created resources to distribute this information so that it could be utilized by the entire neuroscience community.
Recognizing that studying human glia from primary tissue had inherent limitations, Steven completed a post-doctoral fellowship with Dr. Sergiu Pasca at Stanford to develop a human induced pluripotent stem cell 3D model of cortical development called human cortical spheroids (hCS). This is an ideal system for interrogating human cortical development and specifically glial development in both healthy and diseased states. Steven joined the Emory faculty in the fall of 2018, where his lab studies glial development and the role these cells play in neurodevelopmental and neuropsychiatric disease.
In his free time, Steven can be found training for triathlons and spending time outdoors and with his family (including the lab's first two members, canines Kevin and Ben).
Kevin the Dog has never held a pipette before, but he has spent his life perfecting the delivery of moral, emotional, and physical support (snuggles). He looks forward to meeting new people who share his passion for glia and is always willing to give his TED Talk on how 'work-life-balance' should be reframed as 'sleep-life-balance'.
Using 3D organoid cultures to study human astrocytes
Sloan, S.A., Andersen, J., Birey, F., … Pasca, S. Generation and Assembly of Human Brain Region-Specific 3D Cultures (2018) Nature Protocols
Protocol for generating human cortical spheroids
Using sc-RNAseq to find infiltrating GBM cells in human samples
Zhang,Y*, Sloan, S.A.*, Clarke,L., Caneda, C., … Barres, B.A. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. (2016) Neuron *Co-first authors
Purifying human astrocytes and other human CNS cell types
Pasca, A.*, Sloan, S.A.*, Clarke, L., Tian, Y., Makinson, … Barres, B.A., Pasca, S. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D cultures. (2015). Nature Methods *Co-first authors
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Original method for generating human cortical spheroids
Transcriptomic profiling of all major CNS cell types in mouse
Zhang, Y*., Chen, K.*, Sloan, S. A*., Bennett, M. L., Scholze, A. R., … Wu, J. Q. An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex. (2014) The Journal of Neuroscience *Co-first authors
Brosius Lutz, A., Chung, W., Sloan, S.A., … Barres, B.A., Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury (2017). PNAS
Darmanis, S., Sloan, S.A., … Barres, B.A., Quake, S. A survey of human brain transcriptome diversity at the single cell level. (2015) PNAS
Single cell RNAseq of the healthy human brain
Zuchero, B., Fu, M.M., Sloan, S.A., … Barres, B.A. CNS myelin wrapping is driven by myelin basic protein-induced actin disassembly. (2015) Developmental Cell
Lui, H., Zhang, J., … Sloan, S.A., … Barres, B.A., Huang, E.J. Progranulin deficiency promotes circuit-specific synaptic pruning by microglia via complement activation. (2016) Cell
Madelaine, R., Sloan S.A., … Barres, B.A., Mourrain, P. Micro RNA-9 Couples Brain Neurogenesis and Angiogenesis. (2017) Cell Reports
Reviews and Commentaries
Sloan, S. A., Barres, B. A. (2017). Assembling a Cellular User Manual for the Brain. J. Neuroscience
Sloan, S. A., Barres, B. A. (2014b). Looks can be deceiving: reconsidering the evidence for gliotransmission. Neuron
Sloan, S. A., Barres, B. A. (2014). Mechanisms of astrocyte development and their contributions to neurodevelopmental disorders. Current Opinion Neurobiology
Sloan, S. A., Barres, B. A. (2014). The Detrimental Role of Glial Acidification during Ischemia. Neuron
Sloan, S.A., Barres, BA. (2013). Glia as primary drivers of neuropathology in TDP-43 proteinopathies. PNAS
Transcriptomic Databases of Human and Mouse brain
We are seeking motivated, inquisitive , and collaborative people to help us study human neurodevelopment through the lens of glia.
Our goal is to provide a diverse and inclusive working environment in which all scientists can thrive and are treated with respect.
If you are an Emory graduate student interested in learning about opportunities in the lab, please email Steven. If you are looking for a graduate position and you are not at Emory already, you will need to apply to the biosciences graduate program at Emory. More information about program can be found here.
Candidates with an excellent research record and a desire to ask rigorous scientific questions should email Steven with a brief introduction, CV, and the names and contact information of at least two references
We are located at the Emory University campus in Druid Hills, Georgia
Whitehead Biomedical Research Building
615 Michael Street
Atlanta, GA, 30322
Office phone: (941) 228-0511
Fax (Dep of Human Genetics): (404) 727-3949
Cover photo: iDISCO of human cortical spheroid stained for GFAP. Credit: Fikri Birey