OMB No. 0925-0001 and 0925-0002 (Rev. 09/17 Approved Through 03/31/2020)

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FIVE PAGES. NAME: Sloan, Steven Andrew eRA COMMONS USER NAME (credential, e.g., agency login): ssloan999

POSITION TITLE: Assistant Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable. Add/delete rows as necessary.) Completion DEGREE Date FIELD OF STUDY INSTITUTION AND LOCATION (if applicable) MM/YYYY

University of Miami B.S. 05/2010 Biomedical Engineering University of Miami B.S. 05/2010 Biochemistry Stanford University PhD 05/2016 Neurobiology Stanford University MD 01/2018 Medicine Stanford University Postdoctoral Fellow 09/2018 Stem Cells and Neural Development

A. Personal Statement My long-term research interests involve understanding the mechanisms that underlie human brain development, and how these processes are perturbed in disease states like brain cancer. My diverse academic education, research training, and clinical exposure have provided me with a broad foundation and assorted toolset that includes molecular, technical, and clinical skills. While pursuing dual degrees in biomedical engineering and biochemistry at the University of Miami, I gained skills in both quantitative and biological fields. These interests drove me to pursue combined MD/PhD degrees at Stanford University. During my graduate work in Ben Barres’ lab, I focused on understanding the role of human astrocytes and elucidating the transcriptional diversity within the human brain. During my graduate tenure, I was an independent driver of several studies to reveal the transcriptomic landscape of the developing and mature human CNS with an emphasis on human glia and astrocytes. I also coordinated a series of multidisciplinary collaborations to adapt single cell methodologies to the human CNS in both healthy and diseased environments. I then developed novel methods for purifying and culturing human glia, which helped expose previously inaccessible research avenues for investigating human-specific astrocyte functions. In my post-doctoral work with Sergiu Pasca at Stanford University, I led an effort to develop a human induced pluripotent stem cell (iPSC) based methodology for modeling human cortical development using 3D organoid cultures. We then demonstrated the versatility of this platform for interrogating cellular and molecular mechanisms of cortical development and have helped contribute to the burgeoning field of neural organoids. During my clinical training, I gained exposure to the first- hand challenges of managing patients and an understanding for the pressing needs that exist in the clinical arena. I also became immersed in the clinical realm and developed an appreciation for the essential need to integrate translational goals into basic science questions that drive laboratory projects. My work with primary human glia as well as stem cell-based methodologies for modeling human development have helped position me in a unique niche for understanding the fundamental characteristics of human glial development and their role in oncogenic processes like glioblastoma. The Sontag Foundation Distinguished Scientist Award would provide the necessary resources and support to help my new lab at Emory pursue preliminary studies about human astrocyte development and in developing methods for manipulating astrocyte maturation. These data will help build the foundation of the research program that I am trying to create and will serve as the nidus for funding of future large-scale studies.

B. Positions and Honors

Positions and Employment 2018-present Assistant Professor, Department of Human Genetics, Emory University 2018 Postdoctoral Fellow, Department of Psychiatry, Stanford University 2016-2017 Lecturer, Teaching Assistant, Human Health and Disease, Stanford University 2013-2015 Course director, Frontiers in Translational Medicine, Stanford University 2011-2016 Lecturer, Teaching Assistant, Clinical Biochemistry, Stanford University 2011-2013 Lecturer, Step 1 Review Course, Stanford University 2011-2016 Graduate Student, Neurobiology, Stanford University 2008-2010 Instructor, Organic Chemistry Seminar, University of Miami 2011-2016 Medical Student tutor, Stanford University

Other Experience and Professional Memberships 2019-present Member, Center for Neurodysfunction and Inflammation, Emory University School of Medicine 2019-present Curriculum committee, Emory University School of Medicine 2016-2018 Curriculum redesign committee, Stanford University School of Medicine 2013 Advanced Techniques in Molecular Neuroscience Course, Cold Spring Harbor Labs 2011-2018 Stanford University MSTP Student Council Representative 2011- Member, Society for Neuroscience 2010- Member, AAMC (American Academy of Medical Colleges)

Honors 2016 Finalist, Sammy Kuo graduate prize in Neuroscience, Stanford University 2013-2015 Outstanding TA Award, Stanford University School of Medicine, Stanford, CA 2010 Outstanding Senior Award (top graduating student in department), University of Miami 2010 Mortar Board Honor Society, University of Miami 2009 Alpha Eta Mu Beta – Biomedical Engineering Honors Society, University of Miami 2009 Tau Beta Pi – Engineering Honors Society, University of Miami 2008 Phi Beta Kappa – Arts and Sciences Honors Society, University of Miami

C. Contributions to Science

1. My early publications addressed the question of how neuron-glial interactions control CNS development, function, and pathology. To understand how diverse cell-types interact within the brain, I worked to construct an RNAseq transcriptome database of the various murine CNS cell populations. These data provided a molecular landscape of the brain that revealed the degree of molecular partitioning that occurs within the CNS. To supplement this work, I next tailored these techniques to acutely purify each of the major cell types from the human cortex using specimens isolated from neurosurgical resections. Together, I compiled these transcriptional databases into an online resource that is currently used by thousands of scientists worldwide on a daily basis (www.BrainRNASeq.org). In our subsequent work with human samples, we focused specifically on understanding the molecular and functional evolution of human astrocytes—a CNS cell type that plays critical roles in neural circuit formation and development. We discovered two separate human astrocyte maturation states that are molecularly and functionally distinct and contribute uniquely to critical processes of neural circuit development like synapse phagocytosis and neuronal maturation.

a. 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. PMCID: PMC4707064 *Co-first authors

b. Zhang, Y*., Chen, K.*, Sloan, S. A*., Bennett, M. L., Scholze, A. R., O’Keeffe, S., … Wu, J. Q. An RNA-Sequencing Transcriptome and Splicing Database of Glia, Neurons, and Vascular Cells of the Cerebral Cortex. (2014) J Neuroscience. PMCID: PMC4152602 *Co-first authors

c. Sloan, S. A., Barres, B. A. (2018). Assembling a Cellular User Manual for the Brain. J. Neuroscience

d. Sloan, S. A., Barres, B. A. (2014). Mechanisms of astrocyte development and their contributions to neurodevelopmental disorders. Current Opinion Neurobiology.

2. The transcriptional heterogeneity that exists across CNS cell-types is exceedingly diverse. In subsequent work, I established several collaborations to unveil the transcriptional heterogeneity that exits within the human CNS at single cell resolution. We performed these studies first in healthy human brain samples, and then asked how single cell transcriptional landscapes were altered in glioblastoma (GBM) tumors. These studies revealed a previously unknown degree of molecular homology between GBM astrocytes and primary human fetal astrocyte populations, which suggest new therapeutic avenues for treating GBM and underscore the importance of developing methods to understand mechanisms of astrocyte maturation.

a. Darmanis, S*, Sloan, S.A.*, … Quake, S.A. Single-Cell RNAseq analysis of diffuse neoplastic infiltrating cells at the migrating front of human glioblastoma (2017) Cell Reports. PMCID: PMC5810554 *Co-first authors

b. Darmanis, S., Sloan, S.A., … Barres, B.A., Quake, S. A survey of human brain transcriptome diversity at the single cell level. (2015) PNAS. PMCID: PMC4466750

c. Sloan, S. A., Barres, B. A. Looks can be deceiving: reconsidering the evidence for gliotransmission. (2014b) Neuron. PMCID: PMC4433290

d. Gupta, I, Collier, P, Haase, B, …, Sloan, S.A., Luo, W., Fedrigo, O., Ross, E.M., Tilgner, H.U., Single-cell isoform RNA sequencing characterizes isoforms in thousands of cerebellar cells (2018) Nature Biotechnology

3. During my postdoctoral training, I worked with Sergiu Pasca’s lab in the department of Psychiatry at Stanford University to pursue a stem cell-based approach for in vitro modeling of human cortical development. We used induced pluripotent stem cells (iPSCs) to generate a reproducible 3D culture system that generates a laminated cerebral cortex-like structure, named human cortical spheroids (hCS). hCS recapitulate the general 3D cytoarchitecture of the developing human cortex and provide a platform for interrogating cellular and molecular mechanisms of cortical development, with the added benefit that they can be generated from patient-derived samples to investigate specific disease pathologies. After developing this technique, I then used the hCS system as a platform for studying human astrocytes. Not only do iPSC-derived astrocytes demonstrate a high transcriptional fidelity to primary human astrocytes, but by maintaining hCS in culture for over 1.5 years, we were able to observe endogenous maturation of human astrocytes and determine several functional consequences of that process, such as maturation-dependent synapse phagocytosis and non-cell autonomous effects on neuronal activity.

a. Sloan, S.A., Andersen, J., Pasca, A.M., Birey, F., Pasca, S.P. Generation and assembly of human brain region–specific three-dimensional cultures (2018) Nature Protocols

b. Sloan, S.A., Huber, N., Caneda, C., …, Barres, B.A., Pasca, S. Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells. (2017) Neuron. PMCID: PMC5890820

c. Pasca, A.*, Sloan, S.A.*, Clarke, L., Tian, Y., Makinson, … Barres, B.A., Pasca, S. Generation of functional cortical neurons and astrocytes from human pluripotent stem cells in 3D cultures. (2015). Nature Methods. PMCID: PMC4489980 *Co-first authors

d. Marton, R., Miura, Y., Sloan, S.A., … , Pasca, S. Differentiation and maturation of oligodendrocytes in human 3D neural cultures (2019). Nature Neuroscience.

Complete List of Published Work in MyBibliography:

D. Additional Information: Research Support and/or Scholastic Performance

Completed Research Support NIH (NIMH) F30 MH106261 Sloan (PI) 09/08/14-04/18/17 Do Astrocytes Cause Neurodevelopmental Disorders? The goal of this project was to assess whether astrocyte development and dysfunction may contribute to neuropsychiatric disorders such as 22q11 microdeletion syndrome. Role: PI

Stanford BioX Bowes Fellowship Sloan (PI) 05/23/14-05/16/16 Human Astrocytes in Health and Disease The goal of this project was to assess the transcriptional and functional differences between human and rodent astrocytes and to determine whether these could contribute to human-specific neuropsychiatric disorders. Role: PI