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We are interested in understanding the developmental defects resulting from disruptive mutations in novel high-risk genes identified from our ongoing large-scale genomic studies in autism (ASD) and intellectual disability (ID). We take a genetics-first approach for functional analyses in cellular and mouse models and we strive to take into account clinically relevant aspects that emerge from patient-based research.<\/span><\/p>\n

Our current research aims at understanding the cellular and molecular mechanisms underlying DDX3X syndrome, a rare genetic condition associated with ID and ASD manifesting primarily in girls.\u00a0<\/span><\/p>\n

We are part of the<\/span>\u00a0Seaver Autism Center for Research and Treatment <\/a>at the\u00a0<\/span>Icahn School of Medicine at Mount Sinai <\/a>in New York. The Seaver Center is a fully integrated translational research center dedicated to discovering the biological causes of autism\u00a0and\u00a0intellectual disability and developing breakthrough treatments. \u00a0The lab is affiliated to the\u00a0<\/span>Department of Psychiatry,<\/a>\u00a0Mindich Child Health and Development Institute<\/a>\u00a0and\u00a0<\/span>Friedman Brain Institute<\/a>.<\/p>\n

Our group is part of an interdisciplinary\u00a0pre-clinical team of geneticists, molecular biologists, stem cell researchers, and neuroscientists and has direct interactions with a clinical team of psychiatrists, psychologists, neurologists, and clinical geneticists.<\/span><\/p>\n

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De Rubeis Laboratory<\/span>
1468 Madison Avenue<\/span>
Annenberg Building\u00a0<\/span>
Floor 22, Room 38<\/span>
New York, NY 10029<\/span>

<\/span>Office: 212-241-0179<\/span><\/span>
<\/span>silvia.derubeis@mssm.edu<\/a><\/span><\/span><\/p>\n

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Current projects<\/strong><\/span><\/h3>\n

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DDX3X syndrome<\/a> is a recently identified rare form of X-linked ID that accounts for up to 2% of unexplained cases in females. Affected individuals can also present with ASD, hypotonia, movement disorders and brain anomalies.<\/span>
DDX3X syndrome is caused by mutations in the DDX3X<\/i> gene, a gene located on the X chromosome. The gene displays sex differences in its expression. Also, DDX3X mutations display a sexual dichotomy: most mutations are found in females and are not inherited from their parents; the few mutations in males are inherited from apparently asymptomatic mothers.<\/span>
Our research on DDX3X syndrome seeks to elucidate the molecular, cellular and developmental functions of DDX3X to understand how the neurodevelopmental trajectory in DDX3X syndrome goes awry and develop novel therapeutics.<\/span>
Our research aims to address three major questions.<\/span><\/p>\n<\/div>\n

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Individuals with DDX3X syndrome suffers from neurodevelopmental and neurological symptoms. Yet, little is known about the role of DDX3X <\/i>during neurodevelopment and the consequent impact of DDX3X mutations on cognition and social behavior. <\/span>
We are exploring the cellular and molecular functions of DDX3X during brain development taking advantage of a new mouse model of DDX3X syndrome we generated (Ddx3x haploinsufficient females<\/a>). We use standardized behavioral testing in juvenile and adult mice and combine them with cellular and in vivo approaches. Once we identify the mechanisms of DDX3X syndrome and reliable phenotypes in the mouse model, novel therapeutics for DDX3X syndrome can be developed and tested.<\/span><\/p>\n<\/div>\n

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Individuals with DDX3X syndrome are mostly females with de novo mutations, namely mutations that are not transmitted by their parents. The few males with DDX3X syndrome described in the literature inherit their mutations from their mothers, who appear asymptomatic or have subclinical deficits. What determine these sex differences? Why do the mothers of the affected males do not have DDX3X syndrome?<\/span><\/p>\n<\/div>\n

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To address these intriguing questions, we use male and female neuronal models of DDX3X syndrome. We generate male and female embryonic mouse neurons missing DDX3X and study their development and physiology. These models can be used to understand the neurobiology of DDX3X and develop pre-clinical cellular models for drug discovery and testing.<\/span><\/p>\n<\/div>\n<\/div>\n

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DDX3X is an RNA helicase shown to regulate mRNA translation. The role of DDX3X in mRNA translation has been almost exclusively studied in non neuronal cells.<\/span>
In neurons, mRNA translation also occurs at synapses, where it rapidly reshapes the local proteome in response to neuronal activity. Synaptic mRNA translation<\/a> is critical for the formation and plasticity of synapses, and for learning and memory. We use molecular biology and biochemistry techniques to study the molecular complexes and gene targets of DDX3X in neurons, with the goal of identifying new molecular targets for therapeutic intervention. <\/span><\/p>\n<\/div>\n

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Enormous progresses have been made in showing that genetics shapes a large fraction of risk for ASD and in identifying specific genes<\/a> and loci conferring liability. We continue our work with the Autism Sequencing Consortium<\/a><\/span> in aggregating and sequencing large cohorts of individuals with ASD and matched controls collected all over the world. <\/span><\/p>\n<\/div>\n

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Team<\/span><\/h3>\n

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Silvia De Rubeis, Principal Investigator<\/strong><\/span><\/h4>\n

\"\"Silvia is a tenured Associate Professor at the Seaver Autism Center for Research and\u00a0Treatment<\/a>, Department of Psychiatry<\/a>,\u00a0Mindich Child Health\u00a0and\u00a0Development Institute<\/a>, and Friedman Brain Institute<\/a>\u00a0at the Icahn School of Medicine at Mount Sinai<\/a>.<\/span><\/p>\n

Silvia completed her bachelor, master, and PhD degrees in\u00a0Cellular and Molecular Biology at the University of Rome Tor Vergata, Italy.\u00a0During her PhD and first postdoctoral training in Claudia Bagni’s lab at the Katholieke\u00a0Universiteit Leuven and Vlaams Instituut voor Biotechnologie (Belgium), she studied\u00a0how the regulation of mRNA translation shapes\u00a0the\u00a0synaptic development in the\u00a0context of Fragile X syndrome. During this training, she visited Eric Klann’s lab at the New York University as an EMBO short-term fellow.\u00a0She then joined Mount Sinai\u00a0for a second postdoctoral\u00a0training in Joseph Buxbaum’s lab. She studied the role of rare genetic\u00a0variation in autism through large-scale\u00a0exome sequencing.<\/span><\/p>\n

Silvia started her independent research lab in 2017.<\/span><\/p>\n

Silvia is a 2020 Friedman Brain Institute<\/a>\u00a0Scholar Award and a\u00a02021 Distinguished Scholar Award<\/a> from the Icahn School of Medicine at Mount Sinai<\/a>. Silvia also received a\u00a0Wilhelm Bessel Research Award from the Alexander von Humboldt Foundation in 2021.<\/span><\/p>\n

Silvia’s full list of publications here<\/a><\/span>. Silvia describes her role at the Seaver Autism Center for Research and\u00a0Treatment\u00a0here<\/a><\/span>.<\/span><\/p>\n

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Adele joined the lab in July 2020 after a postdoc in Chiara Manzini’s lab. Adele has a PhD in Biomedical Sciences\/Neurosciences at the University of Pavia, in Carlo Sala’s lab. <\/span>Adele studies the role of DDX3X in dendritogenesis, synaptogenesis, and cerebellar development. <\/span><\/span><\/p>\n

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Lauren joined the lab in May 2021 as a graduate student of the Neuroscience program. Lauren graduated from Tulane University with a Bachelor of Science in Neuroscience and a minor in Psychology. Lauren studies the cortical circuits driving motor deficits in DDX3X syndrome.                                    <\/span><\/p>\n

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Marta joined the lab in January 2020 after a PhD in Biomedicine at the University of Barcelona in Esther Perez-Navarro’s lab. Marta studies the cortical development and connectivity in a mouse model of DDX3X syndrome.<\/span><\/span><\/p>\n

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Corinne joined the lab in April 2022 as a graduate student of the Neuroscience program. Corinne graduated from Florida State University (FSU) with a bachelor\u2019s degree in psychology, with minors in biological sciences and chemistry. Corinne is interested in understanding the impact of sensory processing in social behaviors, with a focus on the olfactory system.                                      <\/span><\/p>\n

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Jeronimo joined the lab in July 2022 after a PhD at the Biomedicine Research Institute of Buenos Aires (Partner Institute of Max Planck Society) in Damian Refojo’s lab. Jeronimo<\/span> studies the circuit-level drivers of novelty-elicited behaviors in DDX3X syndrome. <\/span><\/span><\/p>\n

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Nunzio<\/span> joined the lab in May 2025 as a visiting graduate student from the Biomolecular Science program at the Marche Polytechnic University. Nunzio<\/span> obtained a bachelor’s degree in Biological Science and a master’s degree in Molecular and Applied Biology at Marche Polytechnic University in Italy. Nunzio<\/span> studies the biophysical properties of DDX3X and the impact of pathogenic variants in DDX3X.                                 <\/span><\/p>\n

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Alumni<\/span><\/h3>\n

Olivia Pistone<\/p>\n

Mahmuda Hannah<\/p>\n

David Tawfiles<\/p>\n

Yeaji Park<\/span><\/p>\n

Sylvia Maxwell<\/span><\/p>\n

Devina Ung, PhD<\/span><\/p>\n

Danielle Mendonca<\/span><\/p>\n

Andrea Boitnott<\/span><\/p>\n

Carol Eisenberg<\/span><\/p>\n

Ariela Buxbaum Grice<\/span><\/p>\n

Francois Muratet<\/span><\/p>\n

Rocio Villena<\/span><\/p>\n

Amanda de Favre Noguera<\/span><\/p>\n

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\n
\n

Collaborators<\/span><\/h3>\n

Roko-Mladen Rasin, Rutgers University, Robert Wood Johnson Medical School<\/span><\/p>\n

Eric Schmidt, the Rockefeller University<\/span><\/p>\n

Zhuhao Wu, Icahn School of Medicine at Mount Sinai<\/span><\/p>\n

Ki Goosens, Icahn School of Medicine at Mount Sinai\u00a0<\/span><\/p>\n

Daniele Di Marino, Universita\u2019 di Ancona, Italy<\/span><\/p>\n

Nikolaos Daskalakis, McLean Hospital, Department of Psychiatry, Harvard Medical School<\/span><\/p>\n

Paolo Carloni,\u00a0Forschungszentrum J\u00fclich, Germany<\/span><\/p>\n

Joseph Buxbaum, Icahn School of Medicine at Mount Sinai\u00a0<\/span><\/p>\n

Dorothy Grice, Icahn School of Medicine at Mount Sinai\u00a0<\/span><\/p>\n

Michael Breen, Icahn School of Medicine at Mount Sinai\u00a0<\/span><\/p>\n

Claudia Bagni, Universite de Lausanne, Switzerland<\/span><\/p>\n

Ricardo Soto-Rifo, University of Chile, Chile<\/span><\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n<\/div>\n<\/div>\n

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background_mask_color=”#ffffff” background_mask_aspect_ratio=”landscape” background_mask_size=”stretch” background_mask_width=”auto” background_mask_width_tablet=”auto” background_mask_width_phone=”auto” background_mask_height=”auto” background_mask_height_tablet=”auto” background_mask_height_phone=”auto” background_mask_position=”center” background_mask_horizontal_offset=”0px” background_mask_horizontal_offset_tablet=”0px” background_mask_horizontal_offset_phone=”0px” background_mask_vertical_offset=”0px” background_mask_vertical_offset_tablet=”0px” background_mask_vertical_offset_phone=”0px” background_mask_blend_mode=”normal” use_icon_font_size=”off”]<\/p>\n

Mossa A, Dierdorff L, Lukin J, Garcia-Forn M, Wang W, Mamashli F, Park Y, Fiorenzani C, Akpinar Z, Kamps J, Tatzelt J, Wu Z, De Rubeis S. Sex-specific perturbations of neuronal development caused by mutations in the autism risk gene DDX3X.<\/a> Nat Commun. 2025 May 15;16(1):4512. doi: 10.1038\/s41467-025-59680-8. PMID: 40374608; PMCID: PMC12081640.<\/p>\n

Flores MA, Garcia-Forn M, von Mueffling A, Ola P, Park Y, Boitnott A, De Rubeis S. A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X<\/a>. Biol Open. 2025 Jan 15;14(1):bio061854. doi: 10.1242\/bio.061854. Epub 2025 Jan 29. PMID: 39878593; PMCID: PMC11815569.<\/p>\n

Fiorenzani C, Mossa A, De Rubeis S. DEAD\/DEAH-box RNA helicases shape the risk of neurodevelopmental disorders<\/a>. Trends Genet. 2025 May;41(5):437-449. doi:10.1016\/j.tig.2024.12.006. Epub 2025 Jan 18. PMID: 39828505; PMCID: PMC12055483.<\/p>\n

Boitnott A, Garcia-Forn M, Ung DC, Niblo K, Mendonca D, Park Y, Flores M, Maxwell S, Ellegood J, Qiu LR, Grice DE, Lerch JP, Rasin MR, Buxbaum JD, Drapeau E, De Rubeis S. Developmental and Behavioral Phenotypes in a Mouse Model of DDX3X Syndrome<\/a>. Biol Psychiatry. 2021 Dec 1;90(11):742-755. doi:10.1016\/j.biopsych.2021.05.027. Epub 2021 Jun 7. PMID: 34344536; PMCID: PMC8571043.<\/p>\n

Breen MS, Garg P, Tang L, Mendonca D, Levy T, Barbosa M, Arnett AB, Kurtz-Nelson E, Agolini E, Battaglia A, Chiocchetti AG, Freitag CM, Garcia-Alcon A, Grammatico P, Hertz-Picciotto I, Ludena-Rodriguez Y, Moreno C, Novelli A, Parellada M, Pascolini G, Tassone F, Grice DE, Di Marino D, Bernier RA, Kolevzon A, Sharp AJ, Buxbaum JD, Siper PM, De Rubeis S. Episignatures Stratifying Helsmoortel-Van Der Aa Syndrome Show Modest Correlation with Phenotype<\/a>. Am J Hum Genet. 2020 Sep 3;107(3):555-563. doi: 10.1016\/j.ajhg.2020.07.003. Epub 2020 Aug 5. PMID: 32758449; PMCID: PMC7477006.<\/p>\n

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Current Openings\u00a0<\/span><\/h3>\n

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hover_transition_duration_tablet=”300ms” hover_transition_duration_phone=”300ms” hover_transition_delay=”0ms” hover_transition_delay_tablet=”0ms” hover_transition_delay_phone=”0ms” hover_transition_speed_curve=”ease” vertical_offset_tablet=”0″ vertical_offset_phone=”0″ horizontal_offset_tablet=”0″ horizontal_offset_phone=”0″ z_index=”1″ z_index_tablet=”1″ z_index_phone=”1″]<\/p>\n

We are looking for a postdoctoral fellow!<\/p>\n

Postdoc_De Rubeis_2024_FINAL<\/a><\/p>\n

[\/et_pb_accordion_item][\/et_pb_accordion][\/et_pb_column][\/et_pb_row][\/et_pb_section][et_pb_section bb_built=”1″ _builder_version=”4.9.0″ background_color=”rgba(14,128,249,0.21)” prev_background_color=”#ffffff” next_background_color=”#ffffff” box_shadow_horizontal_tablet=”0px” box_shadow_vertical_tablet=”0px” box_shadow_blur_tablet=”40px” box_shadow_spread_tablet=”0px” vertical_offset_tablet=”0″ horizontal_offset_tablet=”0″ background_color_gradient_stops=”#2b87da 0%|#29c4a9 100%”][et_pb_row _builder_version=”4.9.0″ background_size=”initial” background_position=”top_left” background_repeat=”repeat” width=”80%” max_width=”1080px” background_color_gradient_stops=”#2b87da 0%|#29c4a9 100%”][et_pb_column type=”4_4″ custom_padding__hover=”|||” custom_padding=”|||” background_color_gradient_stops=”#2b87da 0%|#29c4a9 100%”][et_pb_text admin_label=”Funding” module_id=”funding” module_class=”funding-section” _builder_version=”4.9.0″ 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Funding<\/span><\/h3>\n

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Beatrice & Samuel Seaver Foundation<\/span><\/p>\n

Eunice Kennedy Shriver<\/em> National Institute of Child Health and Human Development (NICHD)<\/span><\/p>\n

National Institute for Neurological Disorders and Stroke (NINDS)<\/span><\/p>\n

Mindich Child Health and Development Institute<\/span><\/p>\n

Icahn School of Medicine at Mount Sinai<\/span><\/p>\n

Friedman Brain Institute<\/span><\/p>\n

Fundaci\u00f3n Alfonso Mart\u00edn Escudero (to Marta Garcia-Forn)<\/span><\/p>\n

Uplifting Athletes (to Adele Mossa)<\/span><\/p>\n

New York University Dean’s Undergraduate Fund (to Michael Flores)<\/span><\/p>\n

New York University Dean’s Undergraduate Fund (to Zeynep Akpinar)<\/span><\/p>\n

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News and events<\/span><\/h3>\n

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Join the SURS program summer 2025<\/a><\/span>!<\/span><\/h4>\n

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The lab receives a new R21 from NINDS to study cortico-cerebellar communication!<\/span><\/h4>\n

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Watch our new lab video!<\/span><\/h4>\n

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Silvia receives the\u00a0Friedrich Wilhelm Bessel Research Award!<\/span><\/h4>\n

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Adele receives a\u00a02021 Young Investigator Draft from Uplifting Athletes!<\/span><\/h4>\n

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Marta receives a postdoctoral fellowship from Fundaci\u00f3n Alfonso Mart\u00edn Escudero<\/span>!<\/span><\/h4>\n

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Silvia receives a 2021 Distinguished Scholar Award from the Icahn School of Medicine at Mount Sinai<\/span>!<\/span><\/h4>\n

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Silvia receives a 2020 Friedman Brain Institute Scholar Award with Zhuhao Wu<\/span>!<\/span><\/h4>\n

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Follow our Seaver Autism Center Seminar Series here<\/span>!<\/a><\/h4>\n

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Location
<\/strong>Icahn School of Medicine at Mount Sinai
Annenberg 22-38
Phone: 212-241-0179
Office: 212-241-0179
Lab: 212-241-2704
silvia.derubeis@mssm.edu<\/a><\/p>\n

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Related Links<\/strong>
Seaver Autism Center for<\/a><\/span>
Research and Treatment<\/a><\/span>
Mindich Child Health &<\/a><\/span>
Development Institute
Department of Psychiatry
<\/a><\/span>Icahn School of Medicine
<\/a><\/span><\/p>\n

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Related Links<\/strong>
Find a Researcher<\/a>
Research Portal<\/a><\/span><\/p>\n

\u00a0<\/a><\/span><\/p>\n

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Education<\/strong>
Faculty Resources
Student Resources<\/p>\n

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We are interested in understanding the developmental defects resulting from disruptive mutations in novel high-risk genes identified from our ongoing large-scale genomic studies in autism (ASD) and intellectual disability (ID). We take a genetics-first approach for functional analyses in cellular and mouse models and we strive to take into account clinically relevant aspects that emerge […]<\/p>\n","protected":false},"author":274,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_et_pb_use_builder":"on","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"class_list":["post-228","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/pages\/228","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/users\/274"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/comments?post=228"}],"version-history":[{"count":305,"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/pages\/228\/revisions"}],"predecessor-version":[{"id":792,"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/pages\/228\/revisions\/792"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/derubeislab\/wp-json\/wp\/v2\/media?parent=228"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}