Evan Macosko, M.D., Ph.D.

Associate Professor Psychiatry, Massachusetts General Hospital, Institute Member, Broad Institute

Bio: Evan Macosko is an institute member at the Broad Institute of MIT and Harvard, where he directs a lab in the Stanley Center for Psychiatric Research. He is also an associate professor of psychiatry and neurobiology at Harvard Medical School, and attending psychiatrist at Massachusetts General Hospital. He serves as the Co-PI for the BICAN Brain Cell Variation grant. His lab develops new genomics technologies and deploys them to understand pathogenic mechanisms of brain diseases.

Abstract: The advent of next-generation sequencing ushered in a ten-year period of exuberant technology development, enabling the quantification of gene expression and epigenetic features within individual cells, and within intact tissue sections.  In this seminar, I will outline our technological contributions, beginning with the development of Drop-seq, a method for high-throughput single-cell analysis, followed by the development of Slide-seq, a technique for measuring genome-wide expression at 10-micron spatial resolution.  Using a combination of these techniques, we recently constructed a comprehensive cell type atlas of the adult mouse brain, positioning cell types within individual brain structures.  I will discuss the major findings from this dataset, including emerging principles of neurotransmission, and the localization of disease gene signatures to specific cell types.  Finally, I will introduce a new spatial technology, Slide-tags, that unifies single-cell and spatial genomics into a single, highly scalable assay.


Recent Publications: 

Early Alzheimer’s disease pathology in human cortex involves transient cell states.

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.Cell. 2023 Sep 28;186(20):4438-4453.e23. doi: 10.1016/j.cell.2023.08.005.PMID: 37774681
Lackey EP, Moreira L, Norton A, Hemelt ME, Osorno T, Nguyen TM, Macosko EZ, Lee WA, Hull CA, Regehr WG.bioRxiv. 2023 Sep 15:2023.09.15.557934. doi: 10.1101/2023.09.15.557934. Preprint.PMID: 37745401 Free PMC article.

 Cortical somatostatin interneuron subtypes form cell-type-specific circuits.

Wu SJ, Sevier E, Dwivedi D, Saldi GA, Hairston A, Yu S, Abbott L, Choi DH, Sherer M, Qiu Y, Shinde A, Lenahan M, Rizzo D, Xu Q, Barrera I, Kumar V, Marrero G, Prönneke A, Huang S, Kullander K, Stafford DA, Macosko E, Chen F, Rudy B, Fishell G.Neuron. 2023 Sep 6;111(17):2675-2692.e9. doi: 10.1016/j.neuron.2023.05.032. Epub 2023 Jun 29.PMID: 37390821

Thyroid hormone rewires cortical circuits to coordinate body-wide metabolism and exploratory drive.

Hochbaum DR, Dubinsky AC, Farnsworth HC, Hulshof L, Kleinberg G, Urke A, Wang W, Hakim R, Robertson K, Park C, Solberg A, Yang Y, Baynard C, Nadaf NM, Beron CC, Girasole AE, Chantranupong L, Cortopassi M, Prouty S, Geistlinger L, Banks A, Scanlan T, Greenberg ME, Boulting GL, Macosko EZ, Sabatini BL.bioRxiv. 2023 Aug 10:2023.08.10.552874. doi: 10.1101/2023.08.10.552874. Preprint.PMID: 37609206 Free PMC article.


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