Samuel E. Marsh

Bio

I’m a neuroscientist and neuroimmunologist with 10+ years studying neurodegeneration, aging, and neuroimmunology. I have wide-ranging expertise from molecular neuroscience, animal models & behavior, and single-cell and bulk genomics & bioinformatics analyses.

I am currently a postdoctoral fellow in the lab of Dr. Beth Stevens at Boston Children’s Hospital, Harvard Medical School, and Broad Institute. My work centers around understanding immune system dysfunction in Alzheimer’s disease and aging. My current projects are focused on the application single cell genomics technology to understand the gene expression changes that occur during aging and disease. By combining multi-modal single cell genomics with both unbiased and targeted proteomics from brain, CSF, and blood from living patients with neurodegenerative disease we hope to uncover novel disease mechanisms and biomarkers.

My previous project in the Stevens lab was published in Nature Neuroscience in 2022 and detailed a novel protocol for the isolation of microglia (and other cells) while preventing artifacts in the transcriptional data. We also described the potential of related artifacts to occur in data from biopsy and post-mortem human samples. This project used a combination of single-cell genomics, smFISH, and bioinformatic analyses to detail the importance of accounting for cell isolation/post-mortem factors during scRNA-seq analyses.

I did my Ph.D. in the lab of Dr. Mathew Blurton-Jones at the University of California, Irvine. My thesis work focused on the role of the peripheral adaptive immune system in Alzheimer’s disease. My research uncovered a novel role by which peripheral adaptive immune signaling modulates microglial function to alter the pathogenesis of Alzheimer’s disease. I graduated summa cum laude from Northeastern University with B.S. in Behavioral Neuroscience.

Education

The University of California, Irvine | Irvine, CA

Ph.D. in Neurobiology | September 2011 - September 2016

Northeastern University | Boston, MA

B.S. in Behavioral Neuroscience | September 2006 - April 2010

Experience

Boston Children’s Hospital/Harvard Medical School/Broad Institute | Postdoctoral Fellow | September 2017 - Present

The University of California, Irvine | Postdoctoral Fellow | September 2016 - September 2017

Publications

Selected bibliography can be found below and full bibliography can be found here.

Primary Research

Gazestani V, Kamath T, Nadaf NM, Dougalis A, Burris SJ, Rooney B, Junkkari A, Vanderburg C, Pelkonen A, Gomez-Budia M, Välimäki NN, Rauramaa T, Therrien M, Koivisto AM, Tegtmeyer M, Herukka SK, Abdulraouf A, Marsh SE, Hiltunen M, Nehme R, Malm T, Stevens B, Leinonen V, Macosko EZ (2023). Early Alzheimer’s disease pathology in human cortex involves transient cell states. Cell, 186(20):4438–4453.e23. PMID: 37774681. doi.org/10.1016/j.cell.2023.08.005.
Journal Link | Free PDF Full Text | SI Tables | Data Link | Code | PubMed

💥Marsh SE, Walker, AJ, Kamath, T, Dissing-Olesen, L, Hammond, TR, de Soysa, TY, Young, AMH, Murphy, S, Abdulraouf, A, Nadaf, N, Dufort, C, Walker, AC, Lucca, LE, Kozareva, V, Vanderburg, C, Hong, S, Bulstrode, H, Hutchinson, PJ, Gaffney, DJ, Hafler, DA, Franklin, RJM, Macosko, EZ, Stevens, B (2022). Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain. Nature Neuroscience 25(3), 306-316.
Journal Link | Free PDF Full Text | PDF SI Figures & Notes/Discussion | Code | PubMed |

Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J, Marsh SE, Saunders A, Macosko E, Ginhoux F, Chen J, Franklin RJM, Piao X, McCarroll SA, and Stevens B (2019). Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes. Immunity 50(1): 253-271.e6.
Open Access Full Text | PDF Full Text & SI Info | Processed Data Link | PubMed

Abud EM, Ramirez R, Martinez E, Healy L, Nguyen C, Newman S, Yeromin A, Scarfone V, Marsh SE, Fimbres C, Caraway C, Fote G, Mandany A, Agrawal A, Kayed R, Ghylys K, Cahalan M, Cummings B, Antel J, Mortazavi A, Carson M, Poon W, Blurton-Jones M (2017). iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94(2): 278-293.
Open Access Full Text | PDF Full Text & SI Info | PubMed

Marsh SE, Yeung ST, Torres MD, Lau L, Davis JD, Monuki ES, Poon WW, Blurton-Jones M (2017). HuCNS-SC human NSCs fail to terminally differentiate, form ectopic clusters, and provide no cognitive benefits in a transgenic model of Alzheimer’s disease. Stem Cell Reports 8(2):235-248.
Open Access Full Text | PDF Full Text & SI Info | PubMed

💥Marsh SE, Abud, EM, Lakatos A, Karimzadeh A, Yeung ST, Davtyan H, Fote GM, Lau L, Weinger JG, Lane T, Inlay MA, Poon WW, Blurton-Jones M (2016). The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglia function. Proceedings of the National Academy of Sciences USA 113(9):E1316–25.
Open Access Full Text | PDF Full Text | PDF SI Info | PubMed

Reviews

💥Colonna M, Konopka G, Liddelow SA, Nowakowski T, Awatramani R, Bateup HS, Caldwell CR, Caglayan E, Chen JL, Gillis J, Kampmann M, Krienen F, Marsh SE, Monje M, O’Dea MR, Patani R, Pollen AA, Quintana FJ, Scavuzzo M, Schmitz M, Sloan S, Tesar PJ, Tollkuhn J, Tosches MA, Urbanek ME, Werner JM, Bayraktar OA, Gokce O, Habib N (2024; in press). Implementation and validation of single-cell genomics experiments in neuroscience*. Nature Neuroscience.
*Part of series on use of single cell genomics in neuroscience. See here for link to December issue containing other pieces.

💥Liddelow S*, Marsh SE* , Stevens B* (2020). Microglia and astrocytes in health and disease: Dynamic Duo or Partners in Crime? Trends in Immunology 41(9): 820-835.
*Equal Contribution
Journal Link | Free PDF Full Text | PubMed

💥Hammond TR*, Marsh SE*, Stevens B (2019). Immune Signaling in Neurodegeneration. Immunity 50(4): 955-974.
*Equal Contribution
Open Access Full Text | PDF Full Text | PubMed

Marsh SE & Blurton-Jones, M (2012). Examining the mechanisms that link beta-amyloid and alpha-synuclein pathologies. Alzheimer’s Research & Therapy 4(2), 11a.
Open Access Full Text | PDF Full Text | PubMed

Samuel E. Marsh

Bio

I’m a neuroscientist and neuroimmunologist with 10+ years studying neurodegeneration, aging, and neuroimmunology. I have wide-ranging expertise from molecular neuroscience, animal models & behavior, and single-cell and bulk genomics & bioinformatics analyses.

I am currently a postdoctoral fellow in the lab of Dr. Beth Stevens at Boston Children’s Hospital, Harvard Medical School, and Broad Institute. My work centers around understanding immune system dysfunction in Alzheimer’s disease and aging. My current projects are focused on the application single cell genomics technology to understand the gene expression changes that occur during aging and disease. By combining multi-modal single cell genomics with both unbiased and targeted proteomics from brain, CSF, and blood from living patients with neurodegenerative disease we hope to uncover novel disease mechanisms and biomarkers.

My previous project in the Stevens lab was published in Nature Neuroscience in 2022 and detailed a novel protocol for the isolation of microglia (and other cells) while preventing artifacts in the transcriptional data. We also described the potential of related artifacts to occur in data from biopsy and post-mortem human samples. This project used a combination of single-cell genomics, smFISH, and bioinformatic analyses to detail the importance of accounting for cell isolation/post-mortem factors during scRNA-seq analyses.

I did my Ph.D. in the lab of Dr. Mathew Blurton-Jones at the University of California, Irvine. My thesis work focused on the role of the peripheral adaptive immune system in Alzheimer’s disease. My research uncovered a novel role by which peripheral adaptive immune signaling modulates microglial function to alter the pathogenesis of Alzheimer’s disease. I graduated summa cum laude from Northeastern University with B.S. in Behavioral Neuroscience.

Education

The University of California, Irvine | Irvine, CA

Ph.D. in Neurobiology | September 2011 - September 2016

Northeastern University | Boston, MA

B.S. in Behavioral Neuroscience | September 2006 - April 2010

Experience

Boston Children’s Hospital/Harvard Medical School/Broad Institute | Postdoctoral Fellow | September 2017 - Present

The University of California, Irvine | Postdoctoral Fellow | September 2016 - September 2017

Publications

Selected bibliography can be found below and full bibliography can be found here.

Primary Research

Gazestani V, Kamath T, Nadaf NM, Dougalis A, Burris SJ, Rooney B, Junkkari A, Vanderburg C, Pelkonen A, Gomez-Budia M, Välimäki NN, Rauramaa T, Therrien M, Koivisto AM, Tegtmeyer M, Herukka SK, Abdulraouf A, Marsh SE, Hiltunen M, Nehme R, Malm T, Stevens B, Leinonen V, Macosko EZ (2023). Early Alzheimer’s disease pathology in human cortex involves transient cell states. Cell, 186(20):4438–4453.e23. PMID: 37774681. doi.org/10.1016/j.cell.2023.08.005.
Journal Link | Free PDF Full Text | SI Tables | Data Link | Code | PubMed

💥Marsh SE, Walker, AJ, Kamath, T, Dissing-Olesen, L, Hammond, TR, de Soysa, TY, Young, AMH, Murphy, S, Abdulraouf, A, Nadaf, N, Dufort, C, Walker, AC, Lucca, LE, Kozareva, V, Vanderburg, C, Hong, S, Bulstrode, H, Hutchinson, PJ, Gaffney, DJ, Hafler, DA, Franklin, RJM, Macosko, EZ, Stevens, B (2022). Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain. Nature Neuroscience 25(3), 306-316.
Journal Link | Free PDF Full Text | PDF SI Figures & Notes/Discussion | Code | PubMed |

Hammond TR, Dufort C, Dissing-Olesen L, Giera S, Young A, Wysoker A, Walker AJ, Gergits F, Segel M, Nemesh J, Marsh SE, Saunders A, Macosko E, Ginhoux F, Chen J, Franklin RJM, Piao X, McCarroll SA, and Stevens B (2019). Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes. Immunity 50(1): 253-271.e6.
Open Access Full Text | PDF Full Text & SI Info | Processed Data Link | PubMed

Abud EM, Ramirez R, Martinez E, Healy L, Nguyen C, Newman S, Yeromin A, Scarfone V, Marsh SE, Fimbres C, Caraway C, Fote G, Mandany A, Agrawal A, Kayed R, Ghylys K, Cahalan M, Cummings B, Antel J, Mortazavi A, Carson M, Poon W, Blurton-Jones M (2017). iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94(2): 278-293.
Open Access Full Text | PDF Full Text & SI Info | PubMed

Marsh SE, Yeung ST, Torres MD, Lau L, Davis JD, Monuki ES, Poon WW, Blurton-Jones M (2017). HuCNS-SC human NSCs fail to terminally differentiate, form ectopic clusters, and provide no cognitive benefits in a transgenic model of Alzheimer’s disease. Stem Cell Reports 8(2):235-248.
Open Access Full Text | PDF Full Text & SI Info | PubMed

💥Marsh SE, Abud, EM, Lakatos A, Karimzadeh A, Yeung ST, Davtyan H, Fote GM, Lau L, Weinger JG, Lane T, Inlay MA, Poon WW, Blurton-Jones M (2016). The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglia function. Proceedings of the National Academy of Sciences USA 113(9):E1316–25.
Open Access Full Text | PDF Full Text | PDF SI Info | PubMed

Reviews

💥Colonna M, Konopka G, Liddelow SA, Nowakowski T, Awatramani R, Bateup HS, Caldwell CR, Caglayan E, Chen JL, Gillis J, Kampmann M, Krienen F, Marsh SE, Monje M, O’Dea MR, Patani R, Pollen AA, Quintana FJ, Scavuzzo M, Schmitz M, Sloan S, Tesar PJ, Tollkuhn J, Tosches MA, Urbanek ME, Werner JM, Bayraktar OA, Gokce O, Habib N (2024; in press). Implementation and validation of single-cell genomics experiments in neuroscience*. Nature Neuroscience.
*Part of series on use of single cell genomics in neuroscience. See here for link to December issue containing other pieces.

💥Liddelow S*, Marsh SE* , Stevens B* (2020). Microglia and astrocytes in health and disease: Dynamic Duo or Partners in Crime? Trends in Immunology 41(9): 820-835.
*Equal Contribution
Journal Link | Free PDF Full Text | PubMed

💥Hammond TR*, Marsh SE*, Stevens B (2019). Immune Signaling in Neurodegeneration. Immunity 50(4): 955-974.
*Equal Contribution
Open Access Full Text | PDF Full Text | PubMed

Marsh SE & Blurton-Jones, M (2012). Examining the mechanisms that link beta-amyloid and alpha-synuclein pathologies. Alzheimer’s Research & Therapy 4(2), 11a.
Open Access Full Text | PDF Full Text | PubMed