The Breen Lab integrates human genetics, large-scale genomics, computational biology and experimental neuroscience to discover molecular mechanisms of human brain development and disease, and translate these discoveries into new therapeutic strategies. Our work has particular strengths in human brain genomics and RNA biology, spanning genetic, transcriptional and post-transcriptional regulation from molecular discovery through functional validation and therapeutic development.
Research Highlights
Nature Neuroscience, 2019. Genetic variation links RNA editing to schizophrenia.
Large-scale human brain genomics revealed widespread dysregulation and genetic control of A-to-I RNA editing in schizophrenia.
Direct comparison of living and postmortem human cortex revealed profound context-dependent differences in RNA editing across cell types, pathways and genetic regulation.
Human fetal brain and cross-cohort analyses revealed ADARB1 overexpression and premature neuronal RNA recoding in trisomy 21.
Research Team
Michael S. Breen, PhD (he/him)
Associate Professor
Michael S. Breen, PhD, is an Associate Professor of Genetics and Genomic Sciences and Psychiatry at the Icahn School of Medicine at Mount Sinai. He leads an interdisciplinary computational and experimental research program investigating how genetic and RNA regulation shape human brain development, disease, and response to treatment.
A central focus of Dr. Breen’s research is A-to-I RNA editing. His laboratory has defined genetic, cellular, developmental, and disease-associated regulation of RNA editing in the human brain, including studies of schizophrenia, brain development, aging and Alzheimer’s disease, and direct comparisons of living and postmortem human brain. More broadly, the laboratory integrates human genetics with large-scale, single-cell and multi-omic genomics, patient-derived neural models, and experimental perturbation to move from human genomic discovery to biological mechanism. Building on these discoveries, the laboratory is developing programmable RNA editing strategies that harness endogenous editing machinery to repair pathogenic transcripts in genetic neurological disease.
Dr. Breen established his laboratory at Mount Sinai in 2019 and leads a multidisciplinary team of computational and experimental scientists. His research program has attracted more than $10 million in federal, foundation, and industry support and has produced nearly 50 peer-reviewed publications spanning human genetics, neuroscience, genomics, and RNA biology. He also works extensively with academic and industry partners on human genomics, biomarkers, and therapeutic development. Dr. Breen is committed to training scientists who can work across disciplinary boundaries and to fostering scientific independence, rigorous thinking, and collaboration across computational and experimental research.
Contact: miguel.rodriguezdls [at] mssm.edu
Contact: Muriel.Li@icahn.mssm.edu
Contact: andy.yang [at] icahn.mssm.edu
- Pardis Amini was a Associate Researcher and is now attending Graduate at Cincinnati Children’s Hospital Medical Center.
- Olga Dmitrichenko was a Associate Researcher and is now attending Graduate at Insel University Hospital Bern, Switzerland.
- Xuanjia (Sinja) Fan was a Associate Researcher/Lab Manager and is now attending Medical School at Penn State,
- Enrico Mossotto was a Postdoctoral Fellow and is now leading genomic research in Industry
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Joshua Senior was a research volunteer from Brooklyn Technical High School and is now attending University.
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Kendall Moore was a SURP student and is currently finishing studies at Santa Clara University studying Neuroscience and Ethnic Studies.
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Sarah Zipkowitz was a Research Volunteer and is currently attending Binghamton University where she is studying Biology and Judaic Studies on the Pre-Med track.
- Gauri Ganesh was a MSc student and is now a bioinformatician in industry.
- Ariela Buxbaum Grice was an Associate Researcher and is now a PhD graduate student.
Our Research
Human Brain Genomics & Neurodevelopmental Disease
We use human genetics and large-scale genomics to define the molecular programs that shape human brain development and understand how these programs are disrupted in neurological and neurodevelopmental disease. Our work integrates transcriptomics, proteomics, genetic variation and patient-derived cellular models across fetal and postnatal development.
Our studies have mapped the temporal organization of the developing human cortical proteome (view here), contributed to defining genetic and transcriptional regulation across the developing human prefrontal cortex (view here), and helped identify genetic risk for autism through the Autism Sequencing Consortium’s large-scale exome sequencing studies (view here).
A major focus of this program is translating human genetic discovery into molecular mechanism in rare neurodevelopmental disorders. Through the Seaver Autism Center, we have investigated disorders including Phelan-McDermid syndrome, ADNP syndrome, DDX3X syndrome and related genetic conditions. These studies span patient-derived neural models of Phelan-McDermid syndrome (view here), multi-omic characterization of genetically defined patient populations (view here), and molecular responses to experimental treatments in children with ADNP syndrome (view here).
RNA regulation in the Human Brain
A central focus of the Breen Laboratory is understanding how A-to-I RNA editing contributes to the molecular and functional diversity of the human brain. We first mapped the global landscape and genetic regulation of RNA editing in schizophrenia (view here), connecting variation in RNA editing with human genetic variation and disease. Subsequent studies defined the cellular and genetic drivers of editing variation across the human brain (view here) and its spatiotemporal regulation throughout human brain development (view here).
More recently, we extended these studies directly into living human brain, demonstrating divergent landscapes of A-to-I editing between living and postmortem human cortex (view here) and identifying neuronal regulatory events preferentially retained in living tissue. We have also shown that trisomy 21 drives ADARB1 overexpression and premature RNA recoding during human fetal brain development (view here), providing a direct link between genetic dosage, RNA editing machinery and altered neuronal recoding in neurodevelopmental disease.
We are particularly interested in RNA editing events affecting neurotransmitter receptors, ion channels and other proteins central to neuronal function, and in determining which regulatory events represent actionable mechanisms of human disease.
Precision RNA therapeutics
Our laboratory develops site-directed RNA editing approaches that harness endogenous ADAR enzymes to modify pathogenic transcripts at the RNA level, providing a potentially programmable and reversible approach to molecular correction without permanently altering genomic DNA. Our therapeutic program integrates large-scale pathogenic-variant prioritization, computational RNA-target and guide design, experimental measurement of editing efficiency and specificity, and functional studies in human cellular models. We are particularly interested in genetic disorders for which targeted RNA editing can restore a functional transcript or protein and provide a direct molecular test of therapeutic rescue.
Immunogenetics of Neurodevelopmental Disorders: Biomarkers & Treatments
Our laboratory has a longstanding program investigating the immunobiology of neurological and neuropsychiatric disorders, including studies of immune dysregulation, environmental exposures and molecular responses associated with disease (see a few examples here, here, here, here). Through the Seaver Autism Center, we have extended this work to investigate the immunogenetics and immunobiology of children with rare genetic neurodevelopmental disorders.
We use high-dimensional genomic and cellular approaches, including single-cell RNA sequencing, proteomics, metabolomics and mass cytometry, to characterize peripheral immune function and identify molecular phenotypes associated with genetically defined disorders. This work has uncovered previously unrecognized immune abnormalities in disorders typically studied primarily in the context of the central nervous system, including immune phenotypes associated with recurrent infection. For example, we have identified molecularly and molecular defined subgroups in ADNP syndrome (view here) and Phelan-McDermid syndrome (view here), helping connect underlying genetic architecture with variation in molecular and clinical phenotypes.
Publications
1. Breen MS†, Tao R, Yang A*, Wang X*, Amini P*, de Los Santos MR*, Brandtjen AC, Deep-Soboslay A, Kaye WH, Hyde TM, Kleinman JE. Convergent molecular signatures across eating disorders and obsessive-compulsive disorder in the human brain. Cell Reports. 2026;45(6).
2. Breen MS†, Yang A*, Wang X, Rodriguez de Los Santos M*, Tao R, Weinberger DR, Kleinman JE, Mihova K, Stancheva G, Savova S, Kaneva R. Trisomy 21 Drives ADARB1 Overexpression and Premature RNA Recoding in the Developing Fetal Brain. Nature Communications. 2026;17(1):2797.
3. Charney AW, Liharska LE, Vornholt E, Valentine A, Lund A, Hashemi A, Thompson RC, Lohrenz T, Johnson JS, Breen MS, Bussola N, Cheng E. A transcriptional program associated with neurotransmission in the living human brain. Molecular Psychiatry. 2026;31(5):2727–2738.
4. Strom NI, Gerring ZF, Galimberti M, Yu D, Halvorsen MW, Abdellaoui A, et al. Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder. Nature Genetics. 2025;57:1–3.
5. Kopell BH, Kaji DA, Liharska LE, Vornholt E, Lund A, Hashemi A, et al., Breen MS. A study of RNA splicing and protein expression in the living human brain. PLOS ONE. 2025;20(10):e0332651.
6. Gigase FA, Suleri A, Isaevska E, Rommel AS, Boekhorst MG, Dmitrichenko O, et al., Breen MS. Inflammatory markers in pregnancy: identifying drivers in four large cohorts. Frontiers in Immunology. 2025;16:1561798.
7. Gigase FA, Boekhorst MM, Suleri A, Rommel AS, Breen MS, Muetzel RL, et al. Maternal immune activation during pregnancy and obstetric outcomes: a population-based cohort study. BJOG. 2025;132.
8. Suleri A, White T, de Witte L, Gigase F, Cecil CA, Jaddoe VW, Breen MS, et al. Maternal immune activation and child brain development: a longitudinal population-based multimodal neuroimaging study. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2025;10(2):222–235.
9. Dailamy A, Lyu W, Nourreddine S, Tong M, Rainaldi J, McDonald D, et al., Breen MS, Mali P. Charting and probing the activity of ADARs in human development and cell-fate specification. Nature Communications. 2024;15:9818.
10. Buxbaum Grice AS*, Sloofman L, Levy T, Walker H, Ganesh G*, Rodriguez de los Santos M*, et al., Breen MS†. Transient peripheral blood transcriptomic response to ketamine treatment in children with ADNP syndrome. Translational Psychiatry. 2024;14:307.
11. Rodriguez de los Santos M*, Kopell BH, Buxbaum Grice A*, Ganesh G*, Yang A*, et al., Breen MS†. Divergent landscapes of A-to-I editing in postmortem and living human brain. Nature Communications. 2024;15:5366.
12. Quinn TP, Hess JL, Marshe VS, Barnett MM, Hauschild AC, Maciukiewicz M, et al., Breen MS; Machine Learning in Psychiatry Consortium. A primer on the use of machine learning to distil knowledge from data in biological psychiatry. Molecular Psychiatry. 2024;29:1–5.
13. Osman A, Mervosh NL, Strat AN, Euston TJ, Zipursky G, Pollak RM*, et al., Breen MS, Kiraly D. Acetate supplementation rescues social deficits and alters transcriptional regulation in prefrontal cortex of Shank3-deficient mice. Brain, Behavior, and Immunity. 2023;114:311–324.
14. Breen MS†, Fan X*, Levy T, Pollak RM, Collins B, Osman A, et al. Large 22q13.3 deletions perturb peripheral transcriptomic and metabolomic profiles in Phelan-McDermid syndrome. Human Genetics and Genomics Advances. 2023;4:100145.
15. Seah C*, Breen MS†, Rusielewicz T, Bader HN, Xu C, Hunter CJ, et al. Modeling gene × environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression. Nature Neuroscience. 2022;25:1434–1445.
16. Cuddleston WH*, Fan X*, Sloofman L, Liang L, Mossotto E*, Moore K*, et al., Breen MS†. Spatiotemporal and genetic regulation of A-to-I editing throughout human brain development. Cell Reports. 2022;41:111585.
17. Cruceanu C, Dony L, Krontira AC, Fischer DS, Roeh S, et al., Breen MS, et al. Cell-type-specific impact of glucocorticoid receptor activation on the developing brain: a cerebral organoid study. American Journal of Psychiatry. 2022;179:375–387.
18. Trubetskoy V, Pardiñas AF, Qi T, Panagiotaropoulou G, et al., Breen MS, et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature. 2022;604:502–508.
19. Cuddleston R*, Li J, Alexy C, Fan X*, Dracheva S, Mukamel EA, Breen MS†. Cellular and genetic drivers of RNA editing variation in the human brain. Nature Communications. 2022;13:2997.
20. Wingo AP, Wang M, Liu J, Breen MS, et al. Brain microRNAs are associated with variation in cognitive trajectory in advanced age. Translational Psychiatry. 2022;12:1–11.
21. Kolevzon A, Breen MS, Siper PM, Halpern D, Frank Y, et al. Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome. Molecular Autism. 2022;13:1–15.
22. Wingo TS, Gerasimov ES, Liu Y, Duong DM, Vattathil SM, et al., Breen MS, et al. Integrating human brain proteomes with genome-wide association data implicates novel proteins in post-traumatic stress disorder. Molecular Psychiatry. 2022;27:3075–3084.
23. Tang L, Levy T, Guillory S, Halpern D, Zweifach J, Giserman-Kiss I, Foss-Feig JH, et al., Breen MS. Prospective and detailed behavioral phenotyping in DDX3X syndrome. Molecular Autism. 2021;12:1–17.
24. Breen MS†, Garg P, Tang L, Mendonca D, Levy T, Barbosa M, Arnett AB, et al. Episignatures stratifying Helsmoortel–Van der Aa syndrome show modest correlation with phenotype. American Journal of Human Genetics. 2020;107(3):555–563.
25. Statterstrom KF, Kosmicki JA, Wang J, Breen MS, De Rubeis S, Joon A, et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell. 2020;180(3):568–584.e23.
26. Breen MS†, Browne A, Hoffman GE, Stathopoulos S, Brennand KJ, Buxbaum JD, Drapeau E. Transcriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism. Molecular Autism. 2020;11:53.
27. Werling DM, Pochareddy S, Choi J, An JY, Sheppard B, Peng M, et al., Breen MS, et al. Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex. Cell Reports. 2020;31:107489.
28. Huckins L, Chatzinakos C, Breen MS, Almeida A, Hoffman GE, Girdhar K, Kellis M, et al. Genetically regulated gene expression in the brain and peripheral tissues associates with PTSD: SNRNP35 as a novel PTSD gene. Cell Reports. 2020;31:107716.
29. Han L, Zhao X, Benton ML, Perumal T, Collins RL, Hoffman GE, et al., Breen MS, Brennand KJ. Functional annotation of rare structural variation in the human brain. Nature Communications. 2020;11:1–13.
30. Sieberts SK, Perumal TM, Carrasquillo MM, Allen M, Reddy JS, Hoffman GE, et al., Breen MS, et al. Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions. Scientific Data. 2020;7:1–11.
31. Breen MS†, Dobbyn A, Li Q, Roussos P, Hoffman GE, Stahl E, et al. Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia. Nature Neuroscience. 2019;22(9):1402–1412.
32. Breen MS, Bierer LM, Daskalakis NP, Bader HN, Makotkine I, Chattopadhyay M, et al. Differential transcriptional response following glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development. Translational Psychiatry. 2019;9:1–13.
33. Kranidioti H, Manolakopoulos S, Kontos G, Breen MS, Kourikou A, Deutsch M, et al. Immunological biomarkers as indicators for outcome after discontinuation of nucleoside analogue therapy in patients with HBeAg-negative chronic hepatitis B. Journal of Viral Hepatitis. 2019;26(6):697–709.
34. Breen MS†, Thomas KG, Baldwin DS, Lipinska G. Modelling PTSD diagnosis using sleep, memory, and adrenergic metabolites: an exploratory machine-learning study. Human Psychopharmacology: Clinical and Experimental. 2019;34:e2691.
35. Golden C, Breen MS, Koro L, Sonar S, Niblo K, Browne A, et al. Disruption of the KH1 domain leads to transcriptional alterations and attentional deficits in rats. Cerebral Cortex. 2019;29(5):2228–2244.
36. Breen MS†, Ozcan S, Ramsey J, Rustogi N, Gottschalk M, Webster MJ, et al. Temporal proteomic profiling of postnatal human cortical development. Translational Psychiatry. 2018;8:267.
37. Breen MS†, Wingo AP, Koen N, Donald K, Zar HJ, Ressler KJ, et al. Gene expression in cord blood links genetic risk for neurodevelopmental disorders with prenatal maternal distress and adverse childhood outcomes. Brain, Behavior, and Immunity. 2018;73:320–330.
38. White C, Beliakova-Bethell N, Lada S, Breen MS, Hurst T, Spina C, et al. Transcriptional modulation of human endogenous retroviruses in primary CD4+ T cells following vorinostat treatment. Frontiers in Immunology. 2018;9:603.
39. Breen MS†, Tylee D, Maihofer A, Neylan T, Mehta D, Binder E, et al. PTSD blood transcriptome mega-analysis: shared inflammatory pathways across biological sex and modes of trauma. Neuropsychopharmacology. 2017;42:469–481.
40. Breen MS†, Uhlmann A, Ozcan S, Chan M, Pinto D, Bahn S, Stein DJ. Parallel changes in serum proteins and diffusion tensor imaging biomarkers in methamphetamine-associated psychosis. Scientific Reports. 2017;7:47333.
41. Breen MS†, White CH, Shekhtman T, Lin K, Looney D, Woelk CH, Kelsoe JR. Identification of lithium-responsive genes and gene networks in bipolar disorder patient-derived lymphoblastoid cell lines. Pharmacogenomics Journal. 2016;16(5):446–453.
42. Breen MS†, Uhlmann A, Nday C, Glatt SJ, Mitt M, Metsalpu A, et al. Candidate gene networks and blood biomarkers of methamphetamine-associated psychosis: an integrative RNA-sequencing report. Translational Psychiatry. 2016;6:e802.
43. Breen MS, Beliakova-Bethell N, Mujica-Parodi L, Carlson J, Ensign W, Woelk CH, et al. Acute psychological stress induces short-term variable immune response. Brain, Behavior, and Immunity. 2016;53:172–182.
44. Breen MS, Stein DJ, Baldwin DS. Systematic review of blood transcriptome profiling and neuropsychiatric disorders: guidelines for biomarker discovery. Human Psychopharmacology: Clinical and Experimental. 2016;31:373–381.
45. Howard JH, Williams BL, Breen MS, Nishiguchi NK. Adaptation to both host and environment in an environmentally transmitted symbiosis: comparative genomics of Vibrio spp. Vie et Milieu – Life and Environment. 2015;65(4):187–200.
46. Wood O, Woo J, Seumois G, Savelyeva N, McCann KJ, Singh D, Breen MS, et al. Gene expression analysis of TIL-rich HPV-driven head and neck tumors reveals a distinct B-cell signature. Oncotarget. 2015;7:56781.
47. Breen MS†, Maihofer A, Glatt SJ, Chandler SD, Tsuang MT, Risbrough VB, et al. Gene networks specific for innate immunity define post-traumatic stress disorder. Molecular Psychiatry. 2015;20(12):1538–1545.
48. Breen MS, Kemena C, Vlasov P, Notredame C, Kondrashov FA. Epistasis as the primary factor in molecular evolution. Nature. 2012;490(7421):535–538.
49. Breen MS, Kondrashov FA. Mitochondrial pathogenic mutations are population-specific. Biology Direct. 2010;5:68.
Computational Tools & Resources
We develop computational methods and interactive resources that transform complex genomic datasets into accessible tools for biological discovery. Our work spans integrative multi-omics, single-cell and cell-type-resolved genomics, long-read transcriptomics, RNA regulation, statistical genetics and machine learning. We make many of these datasets and analytical frameworks available for the broader research community to explore and reuse.
Interactive Resources
DELTA — Human Cortical Development
Explore coordinated transcriptomic and proteomic trajectories across postnatal human cortical development, including gene- and protein-level developmental patterns and molecular networks.
Explore: http://amp.pharm.mssm.edu/DELTA
Trisomy 21 Developing Brain Atlas
Explore transcriptomic and RNA-editing dysregulation in the developing trisomy 21 human brain across harmonized datasets. Query individual genes to examine cross-study effect sizes and heterogeneity, developmental expression trajectories, case-control differences and normative regional brain expression. The resource also provides processed expression matrices, sample metadata and study-level summary data.
Long-Read Isoform Sequencing Across Human Brain Regions and Cell Types
Explore cell-type-resolved full-length transcripts and isoform diversity in the human cortex using PacBio long-read sequencing. The resource enables interactive investigation of transcript structure and alternative isoform usage across major neuronal and glial cell populations.
Seaver Single-Cell Genomics Resource
Explore single-cell RNA-sequencing data from neurodevelopmental studies at the Seaver Autism Center, enabling investigation of cell-type-specific gene expression and molecular heterogeneity across human cellular populations.
Explore: https://breenms.shinyapps.io/scRNA/
DEX-PTSD — Glucocorticoid Response in Immune Cells of Combat Veterans with PTSD
Explore dose-dependent transcriptional responses to glucocorticoid stimulation in peripheral blood immune cells from individuals with and without PTSD. Users can query genes individually to examine dynamic transcriptional responses to dexamethasone and altered glucocorticoid signaling associated with PTSD.
Transcriptional Profiling of FACs sorted Cord Blood Cell Types
Explore cell-type-specific transcriptional profiles in human umbilical cord blood, providing a reference for understanding cellular composition and gene-expression signals within heterogeneous blood transcriptomic datasets.
Available Positions
We strive to maintain an open-minded, creative and productive research environment, and we are fully committed to foster the growth and development of trainees in the wet and dry labs. If you are interested in applying for a position, please send the following information to michael.breen@mssm.edu
• Complete curriculum vitae, including a list of publications.
• A very brief summary of current work and research interests.
• Contact information for two references.
Contact Us
Contact: Depts. Psychiatry, Genetics and Genomic Sciences
ICAHN BUILDING 14-26
Icahn School of Medicine at Mount Sinai
1425 Madison Avenue, Box 1498
New York, NY 10029