[\/et_pb_slide][et_pb_slide heading=”A-to-I RNA editing in the CNS” use_bg_overlay=”off” use_text_overlay=”off” _builder_version=”4.16″ background_color=”#ffffff” use_background_color_gradient=”on” background_color_gradient_stops=”#d92fef 0%|#29c4a9 100%” background_color_gradient_start=”#d92fef” background_image=”https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2019\/07\/BreenMS_CoverImage.jpg” button_on_hover=”on” global_colors_info=”{}” sticky_transition=”on”][\/et_pb_slide][et_pb_slide heading=”Rare developmental disorders and RNA therapeutics” use_bg_overlay=”off” use_text_overlay=”off” _builder_version=”4.16″ header_text_color=”#000000″ background_image=”https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2019\/07\/da17f9a00e1b9fb0995f034a67468d88.jpg” background_enable_image=”on” button_on_hover=”on” background_layout=”light” global_colors_info=”{}” sticky_transition=”on”][\/et_pb_slide][\/et_pb_fullwidth_slider][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”bio” module_class=”bio-section” _builder_version=”4.16″ custom_margin=”||2em|” global_colors_info=”{}”][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
Laboratory of A-to-I Editing and Rare Disorders<\/strong><\/h4>\nOur research is centered on unraveling the complexities of RNA editing and the genetics\/genomics underlying brain aging and neurological disorders, with a strong emphasis on rare neurodevelopmental disorders. We employ an integrative approach, drawing from human neurogenetics, computational biology, molecular biology, and cellular neuroscience.<\/p>\n
Research Focus Areas<\/strong>:<\/p>\n1. <\/b>We conduct cutting-edge genomic studies to uncover the mechanisms of monogenic neurodevelopmental disorders.
2. Our team develops oligonucleotide-directed RNA editing therapeutics to address the molecular underpinnings of these disorders.
3.\u00a0We leverage large-scale transcriptomic technologies to dissect the function and regulation of RNA editing in brain development, disease, and aging.<\/p>\n
Lab Culture and Philosophy<\/strong>:<\/p>\nIn our lab, we are committed to fostering a positive<\/strong>, inclusive<\/strong>, and collaborative<\/strong> lab environment that prioritizes professional growth<\/strong> and work\/life balance<\/strong>. As a mentor, I am dedicated to training and inspiring the next generation of scientists, whether they pursue careers in academia or industry – everyone’s journey is different! Ultimately, we aim to enable all lab members to make meaningful scientific contributions while engaging in rigorous, ethical, and innovative research. Our lab thrives as part of a highly collaborative ecosystem, working alongside computational and experimental biologists within the Seaver Autism Center for Research and Treatment, the MINDICH Child Health and Development Institute, and the Departments of Genetics and Genomic Sciences and Psychiatry at Mount Sinai.<\/p>\nResearch Topics<\/strong>:<\/p>\n\n- RNA biology<\/li>\n
- Adenosine-to-Inosine (A-to-I) editing and ADAR<\/li>\n
- Alternative splicing, gene expression, protein function<\/li>\n
- Antisense oligonucleotides (ASOs)<\/li>\n
- Brain development, brain aging, brain\/neurological disorders<\/li>\n
- Autism spectrum disorder and syndromic subtypes<\/li>\n
- Rare disorders<\/li>\n
- Neurodegeneration<\/li>\n
- Immunogenetics of developmental disorders<\/li>\n
- Quantitative trait loci<\/li>\n<\/ul>\n
Genomic Technologies and Methods<\/strong>:<\/p>\nOur lab utilizes a diverse array of cutting-edge technologies and methodologies, including:<\/p>\n
\n\n\n\n\n- Whole-genome and whole-exome sequencing (WGS, WES)<\/li>\n
- DNA methylation arrays<\/li>\n
- Transcriptomics: single-cell RNA-seq, RNA-seq, long-read isoform sequencing<\/li>\n
- Mass spectrometry-based proteomics and metabolomics<\/li>\n
- Multi-omic computational models<\/li>\n
- High performance computing<\/li>\n
- CRISPR interference (CRISPRi)<\/li>\n
- Fluorescence-activated cell and nuclei sorting (FACS\/FANS)<\/li>\n
- Cytometry by Time-of-Flight (CyTOF)<\/li>\n
- Neuronal culturing and hiPSC-derived neuronal model systems<\/li>\n
- Antisense oligonucleotide (ASO) therapeutics<\/li>\n<\/ul>\n
Our mission is to advance the understanding of A-to-I editing biology and its implications in brain health and disease, paving the way for innovative therapeutic interventions.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n
[\/et_pb_text][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
____________________________________________________<\/p>\n
Michael S. Breen, PhD <\/strong>(he\/him)
Associate Professor
<\/em><\/strong>I am the Principal Investigator of a multidisciplinary team at the forefront of human genetics, genomics, computational biology, and cellular neuroscience. My scientific journey began in 2008 at the Center for Genomic Regulation (Barcelona, Spain), where I applied computational biology to investigate molecular epistasis. I later earned a Ph.D. in Genomics and Bioinformatics from the University of Southampton (United Kingdom), focusing on epigenetic and transcriptomic mechanisms underlying neuropsychiatric disorders. In 2016, I undertook postdoctoral training in Molecular Psychiatry and Genomics at the Icahn School of Medicine at Mount Sinai. Building on this foundation, I joined the Faculty at Mount Sinai in 2019, where I established the A-to-I Editing and Rare Disorders Lab within the Departments of Psychiatry and Genetics and Genomic Sciences. Our lab is a proud member of the Seaver Autism Center for Research and Treatment, the MINDICH Child Health and Development Institute, and the Friedman Brain Institute. Together, we are dedicated to advancing the understanding of brain function and disease through innovative and collaborative research.<\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ custom_margin=”6em|||” border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”][\/et_pb_text][et_pb_text admin_label=”profile image” _builder_version=”4.16″ custom_margin=”6em|||” border_radii=”on|2px|2px|2px|2px” locked=”off” global_colors_info=”{}”]<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
<\/p>\n
![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2019\/08\/190517-746-Mario-Morgado-1-220x300.jpg\")
<\/p>\n
<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
\n\n\n\n\n\n\nMiguel Rodriguez de los Santos, PhD <\/strong>(he\/him)<\/div>\nPostdoctoral fellow<\/em><\/strong>
Contact:<\/strong> miguel.rodriguezdls [at] mssm.edu<\/em><\/div>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\nMiguel completed his masters in Molecular Biology at the University of Potsdam, Germany, in which he also studied at the University of Rome \u201cLa Sapienza\u201d, Italy within the ERASMUS exchange program. In his master thesis, he focused on gene editing and on making CRISPR-gene editing more efficient towards homology-directed repair events. Miguel obtained his PhD at the Charit\u00e9, University Medicine in Berlin, Germany, where he worked on CRISPR-engineered mouse models for rare neurodevelopmental disorders. More specifically, Miguel studied the molecular and behavioral outcomes of patient-specific mutations affecting the GPI anchor pathway in mice. In 2022, Miguel joined the Breen Lab at the Icahn School of Medicine at Mount Sinai as a postdoctoral fellow where he is developing novel mutation-tailored therapeutic approaches for autism spectrum disorder and rare genetic subtypes. Outside research, Miguel loves outdoor sports, politics, food and exploring the city.<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n\n\u00a0<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n
\u00a0<\/div>\n\u00a0<\/div>\n\u00a0<\/div>\n![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2023\/01\/IMG_6228-2-scaled.jpg\")
<\/div>\n\u00a0<\/div>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” locked=”off” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
\n\n\n\n\n\n\nPardis Amini <\/strong>(she\/her)<\/div>\nAssociate\u00a0Researcher<\/em><\/strong>
Contact:<\/strong> pardis.amini@mssm.edu<\/div>\n\n\n\n\n\n\nPardis\u00a0is an Associate Researcher in the lab. In 2023, she completed\u00a0her Master\u2019s degree with a focus on\u00a0Cellular and Molecular Biology at the University <\/span>of New Haven. In 2020 she obtained a\u00a0Bachelor\u2019s degree in Genetics from the\u00a0University of Shahrekord in Iran<\/span>. Her interests are focused on medical genetics and genetic disorders, and she has gained both academic industry exposure. She recently interned at<\/span>\u00a0REGENXBIO during the summer of 2022 leading research on Duchenne Muscular Dystrophy\u00a0<\/span>gene therapy. She joined the lab<\/span>\u00a0in September 2022 and is working on antisense oligonucleotide therapeutics for rare developmental disorders. Her long-term ambitions are to enter a<\/span>\u00a0PhD program focused on neurogenetic disorders.<\/span><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n
\u00a0<\/div>\n\u00a0<\/div>\n\u00a0<\/div>\n![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2023\/01\/IMG_6221-2-scaled.jpg\")
<\/div>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” locked=”off” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
\n\n\n\n\n\n\nAndy Yang <\/strong>(he\/him)<\/div>\nBiomedical Sciences Master\u2019s Student<\/strong><\/em>
Contact:<\/strong> andy.yang [at] icahn.mssm.edu<\/div>\n\n\n\n\n\n\nAndy is a Master’s student tin the Biomedical Sciences program and the Icahn School of Medicine at Mount Sinai. He graduated from Crown College in 2022 with a degree in Health Sciences and Medical Biology. In his undergraduate thesis, he focused on identifying potential biomarkers of the senescence-associated secretive in age-associated tumors using bioinformatics. Through his research project, he gained a newfound interest in computational biology and later joined the Breen lab in January 2023 to further his studies in functional genomics. For his research, he is resolving cell type- and isoform-specific RNA editing across the human cortex. In the future, he aims to pursue a PhD in computational biology and to continue on his journey in academia. Outside of research, he enjoys getting lost in music, indulging in good stories, and spending quality time with loved ones over dinner!<\/span><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n
\u00a0<\/div>\n\u00a0<\/div>\n\u00a0<\/div>\n![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2023\/01\/IMG_6180-scaled.jpeg\")
<\/div>\n\u00a0<\/div>\n\u00a0<\/div>\n\u00a0<\/div>\n[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
Olga Dmitrichenko\u00a0<\/strong>(she\/her)<\/div>\nAssociate Researcher<\/strong><\/em>
Contact:<\/strong> olga.dmitrichenko [@] mssm.edu<\/em><\/div>\nAs a health scientist and epidemiologist, Olga’s<\/span>\u00a0work focuses on suboptimal pregnancy and\u00a0neurodevelopmental aspects during childhood, linked with neuroimaging.\u00a0She has worked on the Generation R Cohort at the Erasmus Medical Center in Rotterdam, the Netherlands, and conducted research on eating behaviours in association with brain morphology in children.\u00a0After joining Icahn School of Medicine at Mount Sinai, her work focuses on maternal immune activation and brain outcomes, where she is also part of the\u00a0Women’s Mental Health Program.\u00a0<\/span>Outside research, she enjoys long walks with friends<\/span>\u00a0and art expositions<\/span>.<\/span><\/p>\n[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n
<\/p>\n
![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2023\/10\/Photo_MS_olga.jpg\")
<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
\u00a0<\/div>\nLab Alumni:<\/strong><\/div>\n\n\n\n- Xuanjia (Sinja) Fan<\/strong> was a Associate Researcher\/Lab Manager and is now attending Medical School at Penn State.<\/li>\n
- Enrico Mossotto<\/strong> was a Postdoctoral Fellow and is now leading genomic research in Industry<\/li>\n
- \nJoshua Senior<\/strong> was a research volunteer from Brooklyn Technical High School and is now attending University.<\/div>\n<\/li>\n
- \nKendall Moore<\/strong> was a\u00a0SURP student and is currently finishing studies at Santa Clara University studying Neuroscience and Ethnic Studies.<\/div>\n<\/li>\n
- \nSarah Zipkowitz<\/strong> was a Research Volunteer and is currently attending Binghamton University where she is studying Biology and Judaic Studies on the Pre-Med track.<\/span><\/div>\n<\/li>\n
- Gauri Ganesh<\/strong> was a MSc student and is now a bioinformatician in industry.<\/li>\n
- Ariela Buxbaum Grice<\/strong> was an Associate Researcher and is now a PhD graduate student.<\/li>\n<\/ul>\n<\/div>\n<\/div>\n
[\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”research” module_class=”research-section” _builder_version=”4.16″ background_color=”#ffffff” custom_margin=”-3em|||” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ custom_margin=”||-6em|” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_divider divider_style=”dotted” divider_position=”center” divider_weight=”0.5″ _builder_version=”4.16″ height=”25px” custom_margin=”-5em|||” global_colors_info=”{}”][\/et_pb_divider][et_pb_text admin_label=”Research” module_id=”projects” module_class=”projects-section” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
Our Research<\/h2>\n\u00a0<\/h4>\nGenomics of brain development and neurodevelopmental disorders<\/h4>\n
Our work pioneers large-scale genomic investigations of human cortical developmental, combing genetics, transcriptomics and proteomics (see here<\/a> and here<\/a>). These studies chart the complex spatiotemporal and genetic regulation of gene expression and protein abundance, their functions and timely interactions across fetal and postnatal development. We have also led studies dissecting post-transcriptional A-to-I modifications and their roles in supporting the functional diversity of human brain development (see here<\/a>). In addition, our lab is part of the Autism Sequencing Consortiums (ASC), dedicated to dissecting the genetic architecture of ASD through large-scale whole exome sequencing and de novo<\/em> variant discovery (see here<\/a>). We are also part of the Seaver Autism Center for Research and Treatment at Mount Sinai, where we led a number of studies focused on rare monogenic subtypes of autism (see here<\/a>, a report of transcriptional alterations in hiPSC-derived neurons as a consequence of 22q13.3 sequence variants and deletions in participants with Phelan-McDermid syndrome, and here<\/a>, a report on ketamine-induced transcriptional responses in children with ADNP syndrome).<\/p>\n![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2021\/12\/Figure_1new_KM.png\")
<\/h4>\n\u00a0<\/h4>\nMapping the regulation and function of A-to-I editing in brain health and disease<\/h4>\n
Another component of our work is focused on elucidating highly regulated adenosine-to-inosine (A-to-I) editing sites in the human brain both with the main goal to prioritize RNA editing sites for functional, mechanistic, and RNA therapeutic investigation. Currently, we are tackling aspects of RNA editing regulation across brain development (see here<\/a>), major brain cell types and their genetic regulation (see here<\/a>) and dysregulation in neurological disorders (see our work in schizophrenia here<\/a>). We have also investigated A-to-I editing biology in living human brain tissue (see here<\/a>). Currently, we are focused on three central areas:<\/p>\n\n- First, we aim to uncover A-to-I sites implicated in neurodevelopmental and neurodegenerative disorders using large-scale RNA-seq and snRNA-seq from postmortem brain samples and neuronal cell systems.<\/li>\n
- Second, we seek to examine the functional impact of these RNA editing sites on protein function and cellular phenotypes, and we are specifically focused on sites encoding glutamatergic receptors, ion channels and pumps.<\/li>\n
- Third, we aim to develop site-directed RNA editing approaches for therapeutic correction of disease-related RNA editing sites as well as therapeutic repair of highly penetrant, rare genomic point mutations at the mRNA level.<\/li>\n<\/ol>\n
![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2021\/12\/Figure_701.png\")
<\/h4>\n\u00a0<\/h4>\nImmuno-genetics of neurodevelopmental disorders: biomarkers and treatments<\/h4>\n
We have investigated the immunobiology of major neurological disorders for the past 10 years (see a few examples here<\/a>, here<\/a>, here<\/a>, here<\/a>). In the Seaver Autism Center, we are leveraging this expertise to dissect the immunogenetics and immunobiology of children with rare developmental disorders. Our research in the Center surveys peripheral immune responsivity and function in children with rare syndromic subtypes of autism using high-throughput genomic and cellular techniques, including scRNA-seq, metabolomics, proteomics and cytometry by time of flight. This work has uncovered novel immunodeficiencies that underlie recurrent infections in rare disorders that are typically studied in the context of the central nervous system, thereby providing avenues for biomarker development and new therapeutic interventions to tackle common immune-related phenotypes. Our work has also described novel molecularly defined genetic subtypes in both ADNP syndrome (see here<\/a>)\u00a0and Phelan McDermid Syndrome (see here<\/a>).<\/p>\n![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2022\/10\/Picture1.png\")
<\/p>\n
[\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_5,2_5″ _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”3_5″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”Algorithm Development” module_id=”projects” module_class=”projects-section” _builder_version=”4.16″ link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n
Algorithm Development
<\/em><\/strong><\/h4>\nWe are also interested in solving emerging biological and algorithmic problems, which arise from our studies and others, such as: a) comparative transcriptomics and proteomics; b) modelling transgenerational effects across generations; c) predicting cellular frequencies from heterogeneous biological tissue; d) multi-modal integrative deep machine-learning applications; e) modelling RNA-editing in from heterogeneous RNA-sequencing data; f) gene network reconstruction and multi-modal omic data integrations. In addition to generating new data in support of these aims, we also use just about any high-throughput data we get our hands on in the public domain, which can ultimately be translated into better understanding biology.<\/p>\n
\u00a0<\/h5>\nCheck some of our Rshiny apps:<\/em><\/strong><\/h5>\n\n- Temporal proteomic profiling across postnatal cortical development (see here<\/a><\/em>)<\/li>\n
- Transcriptional response to glucocorticoid stimulations in PBMCs from warfighters (see here<\/a><\/em>)<\/li>\n
- Cell type specific transcriptome profiling in umbilical cord blood (see here<\/a><\/em>)<\/li>\n
- The Seaver scRNA-seq Resource (see here<\/a><\/em>)<\/li>\n<\/ul>\n
[\/et_pb_text][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”seaver” module_class=”seaver-section” _builder_version=”4.16″ background_color=”#ffffff” custom_margin=”-4em|||” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_divider divider_style=”dotted” divider_position=”center” divider_weight=”0.5″ _builder_version=”4.16″ height=”25px” global_colors_info=”{}”][\/et_pb_divider][et_pb_text admin_label=”The Seaver Autism Center for Research and Treatment” module_id=”projects” module_class=”projects-section” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
The Seaver Autism Center for Research and Treatment<\/h2>\n\n![\"\"](\"https:\/\/labs.icahn.mssm.edu\/breenlab\/wp-content\/uploads\/sites\/316\/2020\/04\/JGQffHGY_400x400-300x300.png\")
<\/figure>\n<\/div>\nThe Breen<\/span> Lab is part of the\u00a0Seaver Autism Center for Research and Treatment\u00a0<\/a>at the\u00a0Icahn School of Medicine at Mount Sinai<\/a>. The Seaver Autism Center is a fully integrated, translational research center that leads progressive studies and provides personalized care to individuals with autism and related rare disorders. As a team, we are dedicated to discovering the biological causes of autism and developing breakthrough treatments.
<\/em><\/p>\nAs a part of the Seaver Center, our lab is primarily focused on understanding the cellular and molecular consequences underlying rare syndromic forms of autism, including Phelan McDermid-Syndrome (SHANK3), ADNP syndrome, and FOXP1 syndrome. We also collaborate with groups in the Center that generate genetically modified animal models for these genes as well as human iPSC-derived neurons, which we profile using functional genomic tools. Learn more about the Seaver Center here: https:\/\/icahn.mssm.edu\/research\/seaver<\/a><\/p>\nFollow the Seaver Autism Center on Twitter: <\/strong><\/em><\/p>\n[\/et_pb_text][et_pb_social_media_follow follow_button=”on” _builder_version=”4.16″ custom_margin=”-1em|||” global_colors_info=”{}”][et_pb_social_media_follow_network social_network=”twitter” url=”https:\/\/twitter.com\/SeaverAutism” _builder_version=”4.22.2″ background_color=”#000000″ global_colors_info=”{}” follow_button=”on” url_new_window=”on”]Twitter
\n[\/et_pb_social_media_follow_network][\/et_pb_social_media_follow][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”publications” module_class=”publications-section” _builder_version=”4.16″ background_color=”#e6f7ff” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”publications” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n
Select lab publications<\/h2>\n\n- Divergent landscapes of A-to-I editing in postmortem and living human brain<\/a>. Nature Communications<\/span><\/u><\/em>. (2024).<\/li>\n
- Spatiotemporal and genetic regulation of A-to-I editing throughout human brain development<\/a>. Cell Reports<\/span><\/u><\/em>. (2022).<\/li>\n
- Cellular and genetic drivers of RNA editing variability in the human brain<\/a>. Nature Communications<\/span><\/u><\/em>. (2022)<\/li>\n
- Modeling gene \u00d7 environment interactions in PTSD using human neurons reveals diagnosis-specific glucocorticoid-induced gene expression<\/a>. Nature Neuroscience<\/em><\/span>. (2022)<\/li>\n
- \nEpisignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype<\/a>. The American Journal of Human Genetics<\/em><\/span>. (2020).<\/div>\n<\/li>\n
- \nTranscriptional signatures of participant-derived neural progenitor cells and neurons implicate altered Wnt signaling in Phelan-McDermid syndrome and autism.<\/a> Molecular autism<\/span><\/em>. (2020).<\/div>\n<\/li>\n
- Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism.<\/a>\u00a0<\/span>Cell<\/u><\/em>. (2020)<\/li>\n
- Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia.<\/a> Nature Neuroscience<\/span><\/u><\/em>. <\/span><\/em>(2019).<\/span><\/li>\n
- Differential transcriptional response to glucocorticoid activation in cultured blood immune cells: a novel approach to PTSD biomarker development.<\/a> Translational Psychiatry<\/span><\/u><\/em>
1. <\/b>We conduct cutting-edge genomic studies to uncover the mechanisms of monogenic neurodevelopmental disorders.
2. Our team develops oligonucleotide-directed RNA editing therapeutics to address the molecular underpinnings of these disorders.
3.\u00a0We leverage large-scale transcriptomic technologies to dissect the function and regulation of RNA editing in brain development, disease, and aging.<\/p>\n
Lab Culture and Philosophy<\/strong>:<\/p>\n In our lab, we are committed to fostering a positive<\/strong>, inclusive<\/strong>, and collaborative<\/strong> lab environment that prioritizes professional growth<\/strong> and work\/life balance<\/strong>. As a mentor, I am dedicated to training and inspiring the next generation of scientists, whether they pursue careers in academia or industry – everyone’s journey is different! Ultimately, we aim to enable all lab members to make meaningful scientific contributions while engaging in rigorous, ethical, and innovative research. Our lab thrives as part of a highly collaborative ecosystem, working alongside computational and experimental biologists within the Seaver Autism Center for Research and Treatment, the MINDICH Child Health and Development Institute, and the Departments of Genetics and Genomic Sciences and Psychiatry at Mount Sinai.<\/p>\n Research Topics<\/strong>:<\/p>\n Genomic Technologies and Methods<\/strong>:<\/p>\n Our lab utilizes a diverse array of cutting-edge technologies and methodologies, including:<\/p>\n Our mission is to advance the understanding of A-to-I editing biology and its implications in brain health and disease, paving the way for innovative therapeutic interventions.<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n [\/et_pb_text][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n ____________________________________________________<\/p>\n Michael S. Breen, PhD <\/strong>(he\/him) [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ custom_margin=”6em|||” border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”][\/et_pb_text][et_pb_text admin_label=”profile image” _builder_version=”4.16″ custom_margin=”6em|||” border_radii=”on|2px|2px|2px|2px” locked=”off” global_colors_info=”{}”]<\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n <\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” locked=”off” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” locked=”off” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n As a health scientist and epidemiologist, Olga’s<\/span>\u00a0work focuses on suboptimal pregnancy and\u00a0neurodevelopmental aspects during childhood, linked with neuroimaging.\u00a0She has worked on the Generation R Cohort at the Erasmus Medical Center in Rotterdam, the Netherlands, and conducted research on eating behaviours in association with brain morphology in children.\u00a0After joining Icahn School of Medicine at Mount Sinai, her work focuses on maternal immune activation and brain outcomes, where she is also part of the\u00a0Women’s Mental Health Program.\u00a0<\/span>Outside research, she enjoys long walks with friends<\/span>\u00a0and art expositions<\/span>.<\/span><\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”profile image” _builder_version=”4.16″ border_radii=”on|2px|2px|2px|2px” global_colors_info=”{}”]<\/p>\n <\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_4,1_4″ _builder_version=”4.16″ custom_margin=”-5em|||” global_colors_info=”{}”][et_pb_column type=”3_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”research” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”1_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”research” module_class=”research-section” _builder_version=”4.16″ background_color=”#ffffff” custom_margin=”-3em|||” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ custom_margin=”||-6em|” global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_divider divider_style=”dotted” divider_position=”center” divider_weight=”0.5″ _builder_version=”4.16″ height=”25px” custom_margin=”-5em|||” global_colors_info=”{}”][\/et_pb_divider][et_pb_text admin_label=”Research” module_id=”projects” module_class=”projects-section” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n Our work pioneers large-scale genomic investigations of human cortical developmental, combing genetics, transcriptomics and proteomics (see here<\/a> and here<\/a>). These studies chart the complex spatiotemporal and genetic regulation of gene expression and protein abundance, their functions and timely interactions across fetal and postnatal development. We have also led studies dissecting post-transcriptional A-to-I modifications and their roles in supporting the functional diversity of human brain development (see here<\/a>). In addition, our lab is part of the Autism Sequencing Consortiums (ASC), dedicated to dissecting the genetic architecture of ASD through large-scale whole exome sequencing and de novo<\/em> variant discovery (see here<\/a>). We are also part of the Seaver Autism Center for Research and Treatment at Mount Sinai, where we led a number of studies focused on rare monogenic subtypes of autism (see here<\/a>, a report of transcriptional alterations in hiPSC-derived neurons as a consequence of 22q13.3 sequence variants and deletions in participants with Phelan-McDermid syndrome, and here<\/a>, a report on ketamine-induced transcriptional responses in children with ADNP syndrome).<\/p>\n Another component of our work is focused on elucidating highly regulated adenosine-to-inosine (A-to-I) editing sites in the human brain both with the main goal to prioritize RNA editing sites for functional, mechanistic, and RNA therapeutic investigation. Currently, we are tackling aspects of RNA editing regulation across brain development (see here<\/a>), major brain cell types and their genetic regulation (see here<\/a>) and dysregulation in neurological disorders (see our work in schizophrenia here<\/a>). We have also investigated A-to-I editing biology in living human brain tissue (see here<\/a>). Currently, we are focused on three central areas:<\/p>\n We have investigated the immunobiology of major neurological disorders for the past 10 years (see a few examples here<\/a>, here<\/a>, here<\/a>, here<\/a>). In the Seaver Autism Center, we are leveraging this expertise to dissect the immunogenetics and immunobiology of children with rare developmental disorders. Our research in the Center surveys peripheral immune responsivity and function in children with rare syndromic subtypes of autism using high-throughput genomic and cellular techniques, including scRNA-seq, metabolomics, proteomics and cytometry by time of flight. This work has uncovered novel immunodeficiencies that underlie recurrent infections in rare disorders that are typically studied in the context of the central nervous system, thereby providing avenues for biomarker development and new therapeutic interventions to tackle common immune-related phenotypes. Our work has also described novel molecularly defined genetic subtypes in both ADNP syndrome (see here<\/a>)\u00a0and Phelan McDermid Syndrome (see here<\/a>).<\/p>\n [\/et_pb_text][\/et_pb_column][\/et_pb_row][et_pb_row column_structure=”3_5,2_5″ _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”3_5″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”Algorithm Development” module_id=”projects” module_class=”projects-section” _builder_version=”4.16″ link_option_url_new_window=”on” global_colors_info=”{}”]<\/p>\n We are also interested in solving emerging biological and algorithmic problems, which arise from our studies and others, such as: a) comparative transcriptomics and proteomics; b) modelling transgenerational effects across generations; c) predicting cellular frequencies from heterogeneous biological tissue; d) multi-modal integrative deep machine-learning applications; e) modelling RNA-editing in from heterogeneous RNA-sequencing data; f) gene network reconstruction and multi-modal omic data integrations. In addition to generating new data in support of these aims, we also use just about any high-throughput data we get our hands on in the public domain, which can ultimately be translated into better understanding biology.<\/p>\n [\/et_pb_text][\/et_pb_column][et_pb_column type=”2_5″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”seaver” module_class=”seaver-section” _builder_version=”4.16″ background_color=”#ffffff” custom_margin=”-4em|||” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_divider divider_style=”dotted” divider_position=”center” divider_weight=”0.5″ _builder_version=”4.16″ height=”25px” global_colors_info=”{}”][\/et_pb_divider][et_pb_text admin_label=”The Seaver Autism Center for Research and Treatment” module_id=”projects” module_class=”projects-section” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\n The Breen<\/span> Lab is part of the\u00a0Seaver Autism Center for Research and Treatment\u00a0<\/a>at the\u00a0Icahn School of Medicine at Mount Sinai<\/a>. The Seaver Autism Center is a fully integrated, translational research center that leads progressive studies and provides personalized care to individuals with autism and related rare disorders. As a team, we are dedicated to discovering the biological causes of autism and developing breakthrough treatments. As a part of the Seaver Center, our lab is primarily focused on understanding the cellular and molecular consequences underlying rare syndromic forms of autism, including Phelan McDermid-Syndrome (SHANK3), ADNP syndrome, and FOXP1 syndrome. We also collaborate with groups in the Center that generate genetically modified animal models for these genes as well as human iPSC-derived neurons, which we profile using functional genomic tools. Learn more about the Seaver Center here: https:\/\/icahn.mssm.edu\/research\/seaver<\/a><\/p>\n Follow the Seaver Autism Center on Twitter: <\/strong><\/em><\/p>\n [\/et_pb_text][et_pb_social_media_follow follow_button=”on” _builder_version=”4.16″ custom_margin=”-1em|||” global_colors_info=”{}”][et_pb_social_media_follow_network social_network=”twitter” url=”https:\/\/twitter.com\/SeaverAutism” _builder_version=”4.22.2″ background_color=”#000000″ global_colors_info=”{}” follow_button=”on” url_new_window=”on”]Twitter\n
\n
Associate Professor
<\/em><\/strong>I am the Principal Investigator of a multidisciplinary team at the forefront of human genetics, genomics, computational biology, and cellular neuroscience. My scientific journey began in 2008 at the Center for Genomic Regulation (Barcelona, Spain), where I applied computational biology to investigate molecular epistasis. I later earned a Ph.D. in Genomics and Bioinformatics from the University of Southampton (United Kingdom), focusing on epigenetic and transcriptomic mechanisms underlying neuropsychiatric disorders. In 2016, I undertook postdoctoral training in Molecular Psychiatry and Genomics at the Icahn School of Medicine at Mount Sinai. Building on this foundation, I joined the Faculty at Mount Sinai in 2019, where I established the A-to-I Editing and Rare Disorders Lab within the Departments of Psychiatry and Genetics and Genomic Sciences. Our lab is a proud member of the Seaver Autism Center for Research and Treatment, the MINDICH Child Health and Development Institute, and the Friedman Brain Institute. Together, we are dedicated to advancing the understanding of brain function and disease through innovative and collaborative research.<\/p>\n<\/p>\n
Contact:<\/strong> miguel.rodriguezdls [at] mssm.edu<\/em><\/div>\n<\/div>\n
Contact:<\/strong> pardis.amini@mssm.edu<\/div>\n<\/div>\n
Contact:<\/strong> andy.yang [at] icahn.mssm.edu<\/div>\n<\/div>\n
Contact:<\/strong> olga.dmitrichenko [@] mssm.edu<\/em><\/div>\n<\/p>\n\n
Our Research<\/h2>\n
\u00a0<\/h4>\n
Genomics of brain development and neurodevelopmental disorders<\/h4>\n
<\/h4>\n\u00a0<\/h4>\n
Mapping the regulation and function of A-to-I editing in brain health and disease<\/h4>\n
\n
<\/h4>\n\u00a0<\/h4>\n
Immuno-genetics of neurodevelopmental disorders: biomarkers and treatments<\/h4>\n
<\/p>\nAlgorithm Development
<\/em><\/strong><\/h4>\n\u00a0<\/h5>\n
Check some of our Rshiny apps:<\/em><\/strong><\/h5>\n
\n
The Seaver Autism Center for Research and Treatment<\/h2>\n
<\/figure>\n<\/div>\n
<\/em><\/p>\n
\n[\/et_pb_social_media_follow_network][\/et_pb_social_media_follow][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section fb_built=”1″ module_id=”publications” module_class=”publications-section” _builder_version=”4.16″ background_color=”#e6f7ff” global_colors_info=”{}”][et_pb_row _builder_version=”4.16″ global_colors_info=”{}”][et_pb_column type=”4_4″ _builder_version=”4.16″ custom_padding=”|||” global_colors_info=”{}” custom_padding__hover=”|||”][et_pb_text admin_label=”publications” _builder_version=”4.16″ global_colors_info=”{}”]<\/p>\nSelect lab publications<\/h2>\n
\n