De Rubeis lab

 

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.

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. 

We are part of the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinaiin New York. The Seaver Center is a fully integrated translational research center dedicated to discovering the biological causes of autism and intellectual disability and developing breakthrough treatments.  The lab is affiliated to the Department of Psychiatry, Mindich Child Health and Development Institute and Friedman Brain Institute.

Our group is part of an interdisciplinary pre-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.

Contact Us

De Rubeis Laboratory
1468 Madison Avenue
Annenberg Building 
Floor 22, Room 38
New York, NY 10029

Office: 212-241-0179
silvia.derubeis@mssm.edu

Current projects
DDX3X Syndrome

DDX3X syndrome 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.
DDX3X syndrome is caused by mutations in the DDX3X 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.
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.
Our research aims to address three major questions.

What are the molecular functions of DDX3X? 

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.
In neurons, mRNA translation also occurs at synapses, where it rapidly reshapes the local proteome in response to neuronal activity. Synaptic mRNA translation 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. 

How is DDX3X affecting brain development? 

Individuals with DDX3X syndrome suffers from neurodevelopmental and neurological symptoms. Yet, nothing is known about the role of DDX3Xduring neurodevelopment and the consequent impact of DDX3X mutations on cognition and social behavior. 
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. 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.

What are the determinants of sex specificity of DDX3X syndrome?

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?

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.

ADNP Syndrome

ADNP syndrome, also called Helsmoortel-VanDerAa syndrome, is a rare neurodevelopmental disorder caused by mutations in the ADNP gene. We are working on establishing and investigating the utility of blood-based biomarkers in ADNP syndrome. Biological signatures in easily accessible biospecimens (e.g., blood) offer powerful tools to predict and measure treatment response during clinical trials. Further, blood-based biomarkers can also help uncovering biological pathways altered in affected individuals, thus offering a window into the mechanisms underlying the disorder. 

ASD Genetics

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

Team

Silvia De Rubeis, Principal Investigator

Silvia is an Assistant Professor at the Seaver Autism Center for Research and Treatment, Department of PsychiatryMindich Child Health and Development Institute, and Friedman Brain Institute at the Icahn School of Medicine at Mount Sinai.

Silvia completed her bachelor, master and PhD degrees in Cellular and Molecular Biology at the University of Rome Tor Vergata, Italy. During her PhD and first postdoctoral training in Claudia Bagni’s lab at the Katholieke Universiteit Leuven and Vlaams Instituut voor Biotechnologie (Belgium), she studied how the regulation of mRNA translation shapes the synaptic development in the context of Fragile X syndrome. During this training, she visited Eric Klann’s lab at the New York University as an EMBO short-term fellow. She then joined the Mount Sinai for a second postdoctoral training in Joseph Buxbaum’s lab. She studied the role of rare genetic variation in autism through large-scale exome sequencing.. 

Silvia started her lab in 2017.

 

 

 

Adele Mossa, postdoc

Adele joined the lab in July 2020 after completing a postdoc in Chiara Manzini’s lab. Adele holds a PhD in Biomedical Sciences/Neurosciences at the University of Pavia, in Carlo Sala’s lab. Adele studies the role of DDX3X in synaptogenesis and cerebellar development. Adele is supported by the Seaver Foundation, Uplifting Athletes, and the DDX3X Foundation.

Kristi Niblo, research associate

Kristi joined the lab in 2018. She received a Bachelor’s of Science in Veterinary Technology from Mercy College. She gained New York State licensing as a Veterinary Technologist in 2017 before joining the Seaver Autism Center. Kristi oversees the mouse colonies and support behavioral testing.  

Marta Garcia-Forn, postdoc

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 development and connectivity of the cortex of mice modeling DDX3X syndrome, and their relationship to behavioral deficits. Marta is supported by the Seaver Foundation and Fundación Alfonso Martín Escudero.

Yeaji Park, research associate

Yeaji joined the lab in July 2020 after graduating from Macalester College with a Bachelor’s of Science in Neuroscience and a double minor in Biology and Psychology. Yeaji is working with Adele on understanding the role of DDX3X in synaptogenesis and cerebellar development using cell and mouse models. After her training in the De Rubeis lab, Yeaji intends to pursue medical school.                                                   fhbfhf

Michael Flores | Research Intern

Michael joined the De Rubeis lab in November 2019 and and is currently a junior at New York University studying Biology with a minor in Chemistry and Genetics. Formerly, he worked as a clinical research associate in the Emergency Department of Mount Sinai, where he helped Physicians with ongoing research projects through data analysis and patient enrollment. In addition, he volunteers at the NYC Free Clinic as a Spanish interpreter.

Under Marta’s supervision, Michael is working on the role of DDX3X on corticogenesis and synaptogenesis using the mouse model of DDX3X syndrome. Michael is supported by the New York University Dean’s Undergraduate Research Fund.

Read about Michael’s experience as a Latino student in STEM here.

Zeynep Akpinar | Research Intern
 
Zeynep is a research volunteer in the De Rubeis lab, where she is helping characterize a mouse model of DDX3X syndrome.
 
Zeynep joined the De Rubeis Lab in January 2020, and is currently a freshman at New York University studying Biology and Psychology with a Chemistry minor. Michael is supported by the New York University Dean’s Undergraduate Research Fund.
Read about Zeynep’s experience as a international student from a low-income household here.
 

Sylvia Maxwell | Research Intern

Sylvia joined the De Rubeis lab in November 2018 and is currently a junior at The Bronx High School of Science, where she is a part of the Biology Research Program. 

Under Marta’s and Adele’s supervision, Sylvia is helping research the role of DDX3X on corticogenesis and synaptogenesis using the mouse model of DDX3X syndrome. 

Olivia Pistone | Research Intern

Olivia joined the De Rubeis lab in December 2019 and is currently a junior at Darien School of Science. 

Under the supervision of Marta and Adele, Olivia is helping research the role of DDX3X on corticogenesis and synaptogenesis using the mouse model of DDX3X syndrome. 

Mahmuda Hannan | Research Intern

Mahmuda joined the De Rubeis lab in December 2020. She is currently a junior at the Bronx High School of Science where she takes part in the Biology Research Program.

Under Adele’s supervision, Mahmuda is helping research the role of DDX3X in dendritogenesis and synaptogenesis using the mouse model of DDX3X syndrome. 

Alumni

Ariela Buxbaum Grice
Francois Muratet
Rocio Villena
Amanda de Favre Noguera

Collaborators

Publications

2021

Pavinato L, Trajkova S, Grosso E, Giorgio E, Bruselles A, Radio FC, Pippucci T, Dimartino P, Tartaglia M, Petlichkovski A, De Rubeis S, Buxbaum J, Ferrero GB, Keller R, Brusco A (2021). Expanding the clinical phenotype of the ultra-rare Skraban-Deardorff syndrome: Two novel individuals with WDR26 loss-of-function variants and a literature review. Am J Med Genet A. 2021 Mar 6. doi:
10.1002/ajmg.a.62157. Epub ahead of print. PMID: 33675273.

Siper PM, Layton C, Levy T, Lurie S, Benrey N, Zweifach J, Rowe M, Tang L, Guillory S, Halpern D, Giserman-Kiss I, Del Pilar Trelles M, Foss-Feig JH, De Rubeis S, Tavassoli T, Buxbaum JD, Kolevzon A (2021). Sensory Reactivity Symptoms Are a Core Feature of ADNP Syndrome Irrespective of Autism Diagnosis. Genes (Basel). 2021 Feb 27;12(3):351. doi: 10.3390/genes12030351. PMID: 33673501; PMCID: PMC7997330.

Boitnott A *, Ung D *, Garcia-Forn, M, Kristi N, Mendonca D, Flores M, Maxwell S, Ellegood J, Qiu LR, Grice DE, Lerch JP, Rasin M-R, Buxbaum JD, Drapeau E, De Rubeis S (2021). Developmental and behavioral phenotypes in a new mouse model of DDX3X syndrome. BioRxiv [Preprint] 2021.01.22.427482. Available from: doi.org/10.1101/2021.01.22.427482.

2020

Pavinato L, Villamor-Payà M, Sanchiz-Calvo M, Andreoli C, Gay M, Vilaseca M, Arauz-Garofalo G, Ciolfi A, Bruselles A, Pippucci T, Prota V, Carli D, Giorgio E, Radio FC, Antona V, Giuffrè M, Ranguin K, Colson C, De Rubeis S, Dimartino P, Buxbaum JD, Ferrero GB, Tartaglia M, Martinelli S, Stracker TH, Brusco A. Functional analysis of TLK2 variants and their proximal interactomes implicates impaired kinase activity and chromatin maintenance defects in their pathogenesis. J Med Genet. 2020 Dec 15:jmedgenet-2020-107281. doi:
10.1136/jmedgenet-2020-107281. Epub ahead of print. PMID: 33323470.

Garcia-Forn M*, Boitnott A*, Akpinar Z, De Rubeis S. Linking Autism Risk Genes to Disruption of Cortical Development. Cells. 2020 Nov 18;9(11):E2500. doi: 10.3390/cells9112500. PMID: 33218123. *equal contribution

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. 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. *equal contribution

Popovitchenko T, Park Y, Page NF, Luo X, Krsnik Z, Liu Y, Salamon I, Stephenson JD, Kraushar ML, Volk NL, Patel SM, Wijeratne HRS, Li D, Suthar KS, Wach A, Sun M, Arnold SJ, Akamatsu W, Okano H, Paillard L, Zhang H, Buyske S, Kostovic I, De Rubeis S, Hart RP, Rasin MR. Translational derepression of Elavl4 isoforms at their alternative 5′ UTRs determines neuronal development. Nat Commun. 2020 Apr 3;11(1):1674. doi: 10.1038/s41467-020-15412-8. PMID: 32245946.

Satterstrom FK*, Kosmicki JA*, Wang J*, Breen MS, De Rubeis S, An JY, Peng M, Collins R, Grove J, Klei L, Stevens C, Reichert J, Mulhern MS, Artomov M, Gerges  S, Sheppard B, Xu X, Bhaduri A, Norman U, Brand H, Schwartz G, Nguyen R, Guerrero EE, Dias C; Autism Sequencing Consortium; iPSYCH-Broad Consortium, Betancur C, Cook EH, Gallagher L, Gill M, Sutcliffe JS, Thurm A, Zwick ME, Børglum AD, State MW, Cicek AE, Talkowski ME, Cutler DJ, Devlin B, Sanders SJ, Roeder K, Daly MJ, Buxbaum JD. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism. Cell. 2020 Jan 23. pii:
S0092-8674(19)31398-4. doi: 10.1016/j.cell.2019.12.036. PMID: 31981491. *equal contribution

Mahjani B, Dellenvall K, Grahnat AS, Karlsson G, Tuuliainen A, Reichert J, Mahjani CG, Klei L, De Rubeis S, Reichenberg A, Devlin B, Hultman CM, Buxbaum JD, Sandin S, Grice DE. Cohort profile: Epidemiology and Genetics of Obsessive-compulsive disorder and chronic tic disorders in Sweden (EGOS). Soc Psychiatry Psychiatr Epidemiol. 2020 Jan 6. doi: 10.1007/s00127-019-01822-7. PMID: 31907560.

2019

Sullivan JM, De Rubeis S, Schaefer A. Convergence of spectrums: neuronal gene network states in autism spectrum disorder. Curr Opin Neurobiol. 2019 Jun 17;59:102-111. doi: 10.1016/j.conb.2019.04.011. [Epub ahead of print] Review. PMID: 31220745

Doan RN, Lim ET, De Rubeis S, Betancur C, Cutler DJ, Chiocchetti AG, Overman LM, Soucy A, Goetze S; Autism Sequencing Consortium, Freitag CM, Daly MJ, Walsh CA, Buxbaum JD, Yu TW. Recessive gene disruptions in autism spectrum disorder. Nat Genet. 2019 Jun 17. doi: 10.1038/s41588-019-0433-8. [Epub ahead of print]

Golden CEM, Breen MS, Koro L, Sonar S, Niblo K, Browne A, Burlant N, Di Marino D, De Rubeis S, Baxter MG, Buxbaum JD, Harony-Nicolas H. Deletion of the KH1 Domain of Fmr1 Leads to Transcriptional Alterations and Attentional Deficits in Rats. Cereb Cortex. 2019 Mar 16;. doi: 10.1093/cercor/bhz029. [Epub ahead of print] PubMed PMID: 30877790; PubMed Central PMCID: PMC6458915.

Grove J, Ripke S, Als TD, Mattheisen M, Walters RK, Won H, Pallesen J, Agerbo E, Andreassen OA, Anney R, Awashti S, Belliveau R, Bettella F, Buxbaum JD, Bybjerg-Grauholm J, Bækvad-Hansen M, Cerrato F, Chambert K, Christensen JH, Churchhouse C, Dellenvall K, Demontis D, De Rubeis S, Devlin B, Djurovic S, Dumont AL, Goldstein JI, Hansen CS, Hauberg ME, Hollegaard MV, Hope S, Howrigan DP, Huang H, Hultman CM, Klei L, Maller J, Martin J, Martin AR, Moran JL, Nyegaard M, Nærland T, Palmer DS, Palotie A, Pedersen CB, Pedersen MG, dPoterba T, Poulsen JB, Pourcain BS, Qvist P, Rehnström K, Reichenberg A, Reichert J, Robinson EB, Roeder K, Roussos P, Saemundsen E, Sandin S, Satterstrom FK, Davey Smith G, Stefansson H, Steinberg S, Stevens CR, Sullivan PF, Turley P, Walters GB, Xu X, Stefansson K, Geschwind DH, Nordentoft M, Hougaard DM, Werge T, Mors O, Mortensen PB, Neale BM, Daly MJ, Børglum AD. Identification of common genetic risk variants for autism spectrum disorder. Nat Genet. 2019 Mar;51(3):431-444. doi: 10.1038/s41588-019-0344-8. Epub 2019 Feb 25. PubMed PMID: 30804558; PubMed Central PMCID: PMC6454898.

2018

Wang S, Mandell JD, Kumar Y, Sun N, Morris MT, Arbelaez J, Nasello C, Dong S, Duhn C, Zhao X, Yang Z, Padmanabhuni SS, Yu D, King RA, Dietrich A, Khalifa N, Dahl N, Huang AY, Neale BM, Coppola G, Mathews CA, Scharf JM, Fernandez TV, Buxbaum JD, De Rubeis S, Grice DE, Xing J, Heiman GA, Tischfield JA, Paschou P, Willsey AJ, State MW. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis. Cell Rep. 2018 Sep 25;24(13):3441-3454.e12. doi: 10.1016/j.celrep.2018.08.082. PubMed PMID: 30257206; PubMed Central PMCID: PMC6475626

Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, Malik R, Patsopoulos NA, Ripke S, Wei Z, Yu D, Lee PH, Turley P, Grenier-Boley B, Chouraki V, Kamatani Y, Berr C, Letenneur L, Hannequin D, Amouyel P, Boland A, Deleuze JF, Duron E, Vardarajan BN, Reitz C, Goate AM, Huentelman MJ, Kamboh MI, Larson EB, Rogaeva E, St George-Hyslop P, Hakonarson H, Kukull WA, Farrer LA, Barnes LL, Beach TG, Demirci FY, Head E, Hulette CM, Jicha GA, Kauwe JSK, Kaye JA, Leverenz JB, Levey AI, Lieberman AP, Pankratz VS, Poon WW, Quinn JF, Saykin AJ, Schneider LS, Smith AG, Sonnen JA, Stern RA, Van Deerlin VM, Van Eldik LJ, Harold D, Russo G, Rubinsztein DC, Bayer A, Tsolaki M, Proitsi P, Fox NC, Hampel H, Owen MJ, Mead S, Passmore P, Morgan K, Nöthen MM, Rossor M, Lupton MK, Hoffmann P, Kornhuber J, Lawlor B, McQuillin A, Al-Chalabi A, Bis JC, Ruiz A, Boada M, Seshadri S, Beiser A, Rice K, van der Lee SJ, De Jager PL, Geschwind DH, Riemenschneider M, Riedel-Heller S, Rotter JI, Ransmayr G, Hyman BT, Cruchaga C, Alegret M, Winsvold B, Palta P, Farh KH, Cuenca-Leon E, Furlotte N, Kurth T, Ligthart L, Terwindt GM, Freilinger T, Ran C, Gordon SD, Borck G, Adams HHH, Lehtimäki T, Wedenoja J, Buring JE, Schürks M, Hrafnsdottir M, Hottenga JJ, Penninx B, Artto V, Kaunisto M, Vepsäläinen S, Martin NG, Montgomery GW, Kurki MI, Hämäläinen E, Huang H, Huang J, Sandor C, Webber C, Muller-Myhsok B, Schreiber S, Salomaa V, Loehrer E, Göbel H, Macaya A, Pozo-Rosich P, Hansen T, Werge T, Kaprio J, Metspalu A, Kubisch C, Ferrari MD, Belin AC, van den Maagdenberg AMJM, Zwart JA, Boomsma D, Eriksson N, Olesen J, Chasman DI, Nyholt DR, Avbersek A, Baum L, Berkovic S, Bradfield J, Buono R, Catarino CB, Cossette P, De Jonghe P, Depondt C, Dlugos D, Ferraro TN, French J, Hjalgrim H, Jamnadas-Khoda J, Kälviäinen R, Kunz WS, Lerche H, Leu C, Lindhout D, Lo W, Lowenstein D, McCormack M, Møller RS, Molloy A, Ng PW, Oliver K, Privitera M, Radtke R, Ruppert AK, Sander T, Schachter S, Schankin C, Scheffer I, Schoch S, Sisodiya SM, Smith P, Sperling M, Striano P, Surges R, Thomas GN, Visscher F, Whelan CD, Zara F, Heinzen EL, Marson A, Becker F, Stroink H, Zimprich F, Gasser T, Gibbs R, Heutink P, Martinez M, Morris HR, Sharma M, Ryten M, Mok KY, Pulit S, Bevan S, Holliday E, Attia J, Battey T, Boncoraglio G, Thijs V, Chen WM, Mitchell B, Rothwell P, Sharma P, Sudlow C, Vicente A, Markus H, Kourkoulis C, Pera J, Raffeld M, Silliman S, Boraska Perica V, Thornton LM, Huckins LM, William Rayner N, Lewis CM, Gratacos M, Rybakowski F, Keski-Rahkonen A, Raevuori A, Hudson JI, Reichborn-Kjennerud T, Monteleone P, Karwautz A, Mannik K, Baker JH, O’Toole JK, Trace SE, Davis OSP, Helder SG, Ehrlich S, Herpertz-Dahlmann B, Danner UN, van Elburg AA, Clementi M, Forzan M, Docampo E, Lissowska J, Hauser J, Tortorella A, Maj M, Gonidakis F, Tziouvas K, Papezova H, Yilmaz Z, Wagner G, Cohen-Woods S, Herms S, Julià A, Rabionet R, Dick DM, Ripatti S, Andreassen OA, Espeseth T, Lundervold AJ, Steen VM, Pinto D, Scherer SW, Aschauer H, Schosser A, Alfredsson L, Padyukov L, Halmi KA, Mitchell J, Strober M, Bergen AW, Kaye W, Szatkiewicz JP, Cormand B, Ramos-Quiroga JA, Sánchez-Mora C, Ribasés M, Casas M, Hervas A, Arranz MJ, Haavik J, Zayats T, Johansson S, Williams N, Dempfle A, Rothenberger A, Kuntsi J, Oades RD, Banaschewski T, Franke B, Buitelaar JK, Arias Vasquez A, Doyle AE, Reif A, Lesch KP, Freitag C, Rivero O, Palmason H, Romanos M, Langley K, Rietschel M, Witt SH, Dalsgaard S, Børglum AD, Waldman I, Wilmot B, Molly N, Bau CHD, Crosbie J, Schachar R, Loo SK, McGough JJ, Grevet EH, Medland SE, Robinson E, Weiss LA, Bacchelli E, Bailey A, Bal V, Battaglia A, Betancur C, Bolton P, Cantor R, Celestino-Soper P, Dawson G, De Rubeis S, Duque F, Green A, Klauck SM, Leboyer M, Levitt P, Maestrini E, Mane S, De-Luca DM, Parr J, Regan R, Reichenberg A, Sandin S, Vorstman J, Wassink T, Wijsman E, Cook E, Santangelo S, Delorme R, Rogé B, Magalhaes T, Arking D, Schulze TG, Thompson RC, Strohmaier J, Matthews K, Melle I, Morris D, Blackwood D, McIntosh A, Bergen SE, Schalling M, Jamain S, Maaser A, Fischer SB, Reinbold CS, Fullerton JM, Guzman-Parra J, Mayoral F, Schofield PR, Cichon S, Mühleisen TW, Degenhardt F, Schumacher J, Bauer M, Mitchell PB, Gershon ES, Rice J, Potash JB, Zandi PP, Craddock N, Ferrier IN, Alda M, Rouleau GA, Turecki G, Ophoff R, Pato C, Anjorin A, Stahl E, Leber M, Czerski PM, Cruceanu C, Jones IR, Posthuma D, Andlauer TFM, Forstner AJ, Streit F, Baune BT, Air T, Sinnamon G, Wray NR, MacIntyre DJ, Porteous D, Homuth G, Rivera M, Grove J, Middeldorp CM, Hickie I, Pergadia M, Mehta D, Smit JH, Jansen R, de Geus E, Dunn E, Li QS, Nauck M, Schoevers RA, Beekman AT, Knowles JA, Viktorin A, Arnold P, Barr CL, Bedoya-Berrio G, Bienvenu OJ, Brentani H, Burton C, Camarena B, Cappi C, Cath D, Cavallini M, Cusi D, Darrow S, Denys D, Derks EM, Dietrich A, Fernandez T, Figee M, Freimer N, Gerber G, Grados M, Greenberg E, Hanna GL, Hartmann A, Hirschtritt ME, Hoekstra PJ, Huang A, Huyser C, Illmann C, Jenike M, Kuperman S, Leventhal B, Lochner C, Lyon GJ, Macciardi F, Madruga-Garrido M, Malaty IA, Maras A, McGrath L, Miguel EC, Mir P, Nestadt G, Nicolini H, Okun MS, Pakstis A, Paschou P, Piacentini J, Pittenger C, Plessen K, Ramensky V, Ramos EM, Reus V, Richter MA, Riddle MA, Robertson MM, Roessner V, Rosário M, Samuels JF, Sandor P, Stein DJ, Tsetsos F, Van Nieuwerburgh F, Weatherall S, Wendland JR, Wolanczyk T, Worbe Y, Zai G, Goes FS, McLaughlin N, Nestadt PS, Grabe HJ, Depienne C, Konkashbaev A, Lanzagorta N, Valencia-Duarte A, Bramon E, Buccola N, Cahn W, Cairns M, Chong SA, Cohen D, Crespo-Facorro B, Crowley J, Davidson M, DeLisi L, Dinan T, Donohoe G, Drapeau E, Duan J, Haan L, Hougaard D, Karachanak-Yankova S, Khrunin A, Klovins J, Kučinskas V, Lee Chee Keong J, Limborska S, Loughland C, Lönnqvist J, Maher B, Mattheisen M, McDonald C, Murphy KC, Nenadic I, van Os J, Pantelis C, Pato M, Petryshen T, Quested D, Roussos P, Sanders AR, Schall U, Schwab SG, Sim K, So HC, Stögmann E, Subramaniam M, Toncheva D, Waddington J, Walters J, Weiser M, Cheng W, Cloninger R, Curtis D, Gejman PV, Henskens F, Mattingsdal M, Oh SY, Scott R, Webb B, Breen G, Churchhouse C, Bulik CM, Daly M, Dichgans M, Faraone SV, Guerreiro R, Holmans P, Kendler KS, Koeleman B, Mathews CA, Price A, Scharf J, Sklar P, Williams J, Wood NW, Cotsapas C, Palotie A, Smoller JW, Sullivan P, Rosand J, Corvin A, Neale BM, Schott JM, Anney R, Elia J, Grigoroiu-Serbanescu M, Edenberg HJ, Murray R. Analysis of shared heritability in common disorders of the brain.  Science. 2018 Jun 22;360(6395). doi: 10.1126/science.aap8757. PubMed PMID: 29930110; PubMed Central PMCID: PMC6097237.

Barbosa M, Joshi RS, Garg P, Martin-Trujillo A, Patel N, Jadhav B, Watson CT, Gibson W, Chetnik K, Tessereau C, Mei H, De Rubeis S, Reichert J, Lopes F, Vissers LELM, Kleefstra T, Grice DE, Edelmann L, Soares G, Maciel P, Brunner HG, Buxbaum JD, Gelb BD, Sharp AJ. Identification of rare de novo epigenetic variations in congenital disorders.Nat Commun. 2018 May 25;9(1):2064. doi: 10.1038/s41467-018-04540-x. PubMed PMID: 29802345; PubMed Central PMCID: PMC5970273.

De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018;9:31. doi: 10.1186/s13229-018-0205-9. eCollection 2018. PubMed PMID: 29719671; PubMed Central PMCID: PMC5921983.

2017

Golden CE, Buxbaum JD, De Rubeis S. Disrupted circuits in mouse models of autism spectrum disorder and intellectual disability. Curr Opin Neurobiol. 2018 Feb;48:106-112. doi: 10.1016/j.conb.2017.11.006. Epub 2017 Dec 7. Review. PubMed PMID: 29222989; PubMed Central PMCID: PMC5825272

Siper PM, De Rubeis S, Trelles MDP, Durkin A, Di Marino D, Muratet F, Frank Y, Lozano R, Eichler EE, Kelly M, Beighley J, Gerdts J, Wallace AS, Mefford HC, Bernier RA, Kolevzon A, Buxbaum JD. Prospective investigation of FOXP1 syndrome. Mol Autism. 2017;8:57. doi: 10.1186/s13229-017-0172-6. eCollection 2017. PubMed PMID: 29090079; PubMed Central PMCID: PMC5655854.

Di Gregorio E, Riberi E, Belligni EF, Biamino E, Spielmann M, Ala U, Calcia A, Bagnasco I, Carli D, Gai G, Giordano M, Guala A, Keller R, Mandrile G, Arduino C, Maffè A, Naretto VG, Sirchia F, Sorasio L, Ungari S, Zonta A, Zacchetti G, Talarico F, Pappi P, Cavalieri S, Giorgio E, Mancini C, Ferrero M, Brussino A, Savin E, Gandione M, Pelle A, Giachino DF, De Marchi M, Restagno G, Provero P, Cirillo Silengo M, Grosso E, Buxbaum JD, Pasini B, De Rubeis S, Brusco A, Ferrero GB. Copy number variants analysis in a cohort of isolated and syndromic developmental delay/intellectual disability reveals novel genomic disorders, position effects and candidate disease genes. Clin Genet. 2017 Oct;92(4):415-422. doi: 10.1111/cge.13009. Epub 2017 Jul 25. PubMed PMID: 28295210.

Varghese M, Keshav N, Jacot-Descombes S, Warda T, Wicinski B, Dickstein DL, Harony-Nicolas H, De Rubeis S, Drapeau E, Buxbaum JD, Hof PR. Autism spectrum disorder: neuropathology and animal models. Acta Neuropathol. 2017 Oct;134(4):537-566. doi: 10.1007/s00401-017-1736-4. Epub 2017 Jun 5. Review. PubMed PMID: 28584888; PubMed Central PMCID: PMC5693718.

Lim ET, Uddin M, De Rubeis S, Chan Y, Kamumbu AS, Zhang X, D’Gama AM, Kim SN, Hill RS, Goldberg AP, Poultney C, Minshew NJ, Kushima I, Aleksic B, Ozaki N, Parellada M, Arango C, Penzol MJ, Carracedo A, Kolevzon A, Hultman CM, Weiss LA, Fromer M, Chiocchetti AG, Freitag CM, Church GM, Scherer SW, Buxbaum JD, Walsh CA. Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder. Nat Neurosci. 2017 Sep;20(9):1217-1224. doi: 10.1038/nn.4598. Epub 2017 Jul 17. PubMed PMID: 28714951; PubMed Central PMCID: PMC5672813.

Weiner DJ, Wigdor EM, Ripke S, Walters RK, Kosmicki JA, Grove J, Samocha KE, Goldstein JI, Okbay A, Bybjerg-Grauholm J, Werge T, Hougaard DM, Taylor J, Skuse D, Devlin B, Anney R, Sanders SJ, Bishop S, Mortensen PB, Børglum AD, Smith GD, Daly MJ, Robinson EB. Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders. Nat Genet. 2017 Jul;49(7):978-985. doi: 10.1038/ng.3863. Epub 2017 May 15. PubMed PMID: 28504703; PubMed Central PMCID: PMC5552240.

Alfieri A, Sorokina O, Adrait A, Angelini C, Russo I, Morellato A, Matteoli M, Menna E, Boeri Erba E, McLean C, Armstrong JD, Ala U, Buxbaum JD, Brusco A, Couté Y, De Rubeis S, Turco E, Defilippi P. Synaptic Interactome Mining Reveals p140Cap as a New Hub for PSD Proteins Involved in Psychiatric and Neurological Disorders. Front Mol Neurosci.2017;10:212. doi: 10.3389/fnmol.2017.00212. eCollection 2017. PubMed PMID: 28713243; PubMed Central PMCID: PMC5492163.

Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia. Mol Autism. 2017;8:21. doi: 10.1186/s13229-017-0137-9. eCollection 2017. PubMed PMID: 28540026; PubMed Central PMCID: PMC5441062.

2016

Biamino E, Di Gregorio E, Belligni EF, Keller R, Riberi E, Gandione M, Calcia A, Mancini C, Giorgio E, Cavalieri S, Pappi P, Talarico F, Fea AM, De Rubeis S, Cirillo Silengo M, Ferrero GB, Brusco A. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity. Am J Med Genet B Neuropsychiatr Genet. 2016 Mar;171B(2):290-9. doi: 10.1002/ajmg.b.32406. Epub 2015 Dec 1. PubMed PMID: 26620927.

2015

Biamino E, Di Gregorio E, Belligni EF, Keller R, Riberi E, Gandione M, Calcia A, Mancini C, Giorgio E, Cavalieri S, Pappi P, Talarico F, Fea AM, De Rubeis S, Cirillo Silengo M, Ferrero GB, Brusco A. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity. Am J Med Genet B Neuropsychiatr Genet. 2016 Mar;171B(2):290-9. doi: 10.1002/ajmg.b.32406. Epub 2015 Dec 1. PubMed PMID: 26620927.

Harony-Nicolas H, De Rubeis S, Kolevzon A, Buxbaum JD. Phelan McDermid Syndrome: From Genetic Discoveries to Animal Models and Treatment. J Child Neurol. 2015 Dec;30(14):1861-70. doi: 10.1177/0883073815600872. Epub 2015 Sep 8. Review. PubMed PMID: 26350728; PubMed Central PMCID: PMC5321557.

De Rubeis S, Buxbaum JD. Genetics and genomics of autism spectrum disorder: embracing complexity. Hum Mol Genet.2015 Oct 15;24(R1):R24-31. doi: 10.1093/hmg/ddv273. Epub 2015 Jul 17. Review. PubMed PMID: 26188008; PubMed Central PMCID: PMC4675826.

Kozol RA, Cukier HN, Zou B, Mayo V, De Rubeis S, Cai G, Griswold AJ, Whitehead PL, Haines JL, Gilbert JR, Cuccaro ML, Martin ER, Baker JD, Buxbaum JD, Pericak-Vance MA, Dallman JE. Two knockdown models of the autism genes SYNGAP1 and SHANK3 in zebrafish produce similar behavioral phenotypes associated with embryonic disruptions of brain morphogenesis. Hum Mol Genet. 2015 Jul 15;24(14):4006-23. doi: 10.1093/hmg/ddv138. Epub 2015 Apr 16. PubMed PMID: 25882707; PubMed Central PMCID: PMC4476447.

Di Marino D, Chillemi G, De Rubeis S, Tramontano A, Achsel T, Bagni C. MD and Docking Studies Reveal That the Functional Switch of CYFIP1 is Mediated by a Butterfly-like Motion. J Chem Theory Comput. 2015 Jul 14;11(7):3401-10. doi: 10.1021/ct500431h. PubMed PMID: 26575774.

Fernández E, Li KW, Rajan N, De Rubeis S, Fiers M, Smit AB, Achsel T, Bagni C. FXR2P Exerts a Positive Translational Control and Is Required for the Activity-Dependent Increase of PSD95 Expression. J Neurosci. 2015 Jun 24;35(25):9402-8. doi: 10.1523/JNEUROSCI.4800-14.2015. PubMed PMID: 26109663.

De Rubeis S, Buxbaum JD. Recent advances in the genetics of autism spectrum disorder. Curr Neurol Neurosci Rep. 2015 Jun;15(6):36. doi: 10.1007/s11910-015-0553-1. Review. PubMed PMID: 25946996.

Braat S, D’Hulst C, Heulens I, De Rubeis S, Mientjes E, Nelson DL, Willemsen R, Bagni C, Van Dam D, De Deyn PP, Kooy RF. The GABAA receptor is an FMRP target with therapeutic potential in fragile X syndrome. Cell Cycle. 2015;14(18):2985-95. doi: 10.4161/15384101.2014.989114. PubMed PMID: 25790165; PubMed Central PMCID: PMC4827888.

2014

Ionita-Laza I, Capanu M, De Rubeis S, McCallum K, Buxbaum JD. Identification of rare causal variants in sequence-based studies: methods and applications to VPS13B, a gene involved in Cohen syndrome and autism. PLoS Genet. 2014 Dec;10(12):e1004729. doi: 10.1371/journal.pgen.1004729. eCollection 2014 Dec. PubMed PMID: 25502226; PubMed Central PMCID: PMC4263785.

De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Cicek AE, Kou Y, Liu L, Fromer M, Walker S, Singh T, Klei L, Kosmicki J, Shih-Chen F, Aleksic B, Biscaldi M, Bolton PF, Brownfeld JM, Cai J, Campbell NG, Carracedo A, Chahrour MH, Chiocchetti AG, Coon H, Crawford EL, Curran SR, Dawson G, Duketis E, Fernandez BA, Gallagher L, Geller E, Guter SJ, Hill RS, Ionita-Laza J, Jimenz Gonzalez P, Kilpinen H, Klauck SM, Kolevzon A, Lee I, Lei I, Lei J, Lehtimäki T, Lin CF, Ma’ayan A, Marshall CR, McInnes AL, Neale B, Owen MJ, Ozaki N, Parellada M, Parr JR, Purcell S, Puura K, Rajagopalan D, Rehnström K, Reichenberg A, Sabo A, Sachse M, Sanders SJ, Schafer C, Schulte-Rüther M, Skuse D, Stevens C, Szatmari P, Tammimies K, Valladares O, Voran A, Li-San W, Weiss LA, Willsey AJ, Yu TW, Yuen RK, Cook EH, Freitag CM, Gill M, Hultman CM, Lehner T, Palotie A, Schellenberg GD, Sklar P, State MW, Sutcliffe JS, Walsh CA, Scherer SW, Zwick ME, Barett JC, Cutler DJ, Roeder K, Devlin B, Daly MJ, Buxbaum JD. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014 Nov 13;515(7526):209-15. doi: 10.1038/nature13772. Epub 2014 Oct 29. PubMed PMID: 25363760; PubMed Central PMCID: PMC4402723.

2013

Poultney CS, Goldberg AP, Drapeau E, Kou Y, Harony-Nicolas H, Kajiwara Y, De Rubeis S, Durand S, Stevens C, Rehnström K, Palotie A, Daly MJ, Ma’ayan A, Fromer M, Buxbaum JD. Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder. Am J Hum Genet. 2013 Oct 3;93(4):607-19. doi: 10.1016/j.ajhg.2013.09.001. PubMed PMID: 24094742; PubMed Central PMCID: PMC3791269.

De Rubeis S, Pasciuto E, Li KW, Fernández E, Di Marino D, Buzzi A, Ostroff LE, Klann E, Zwartkruis FJ, Komiyama NH, Grant SG, Poujol C, Choquet D, Achsel T, Posthuma D, Smit AB, Bagni C. CYFIP1 coordinates mRNA translation and cytoskeleton remodeling to ensure proper dendritic spine formation. Neuron. 2013 Sep 18;79(6):1169-82. doi: 10.1016/j.neuron.2013.06.039. PubMed PMID: 24050404; PubMed Central PMCID: PMC3781321.

He X, Sanders SJ, Liu L, De Rubeis S, Lim ET, Sutcliffe JS, Schellenberg GD, Gibbs RA, Daly MJ, Buxbaum JD, State MW, Devlin B, Roeder K. Integrated model of de novo and inherited genetic variants yields greater power to identify risk genes. PLoS Genet. 2013;9(8):e1003671. doi: 10.1371/journal.pgen.1003671. Epub 2013 Aug 15. PubMed PMID: 23966865; PubMed Central PMCID: PMC3744441.

2012

De Rubeis S, Fernández E, Buzzi A, Di Marino D, Bagni C. Molecular and cellular aspects of mental retardation in the Fragile X syndrome: from gene mutation/s to spine dysmorphogenesis. Adv Exp Med Biol. 2012;970:517-51. doi: 10.1007/978-3-7091-0932-8_23. Review. PubMed PMID: 22351071.

2011 & Earlier

De Rubeis S, Bagni C. Regulation of molecular pathways in the Fragile X Syndrome: insights into Autism Spectrum Disorders. J Neurodev Disord. 2011 Sep;3(3):257-69. doi: 10.1007/s11689-011-9087-2. Epub 2011 Aug 13. PubMed PMID: 21842222; PubMed Central PMCID: PMC3167042.

Tassone F, De Rubeis S, Carosi C, La Fata G, Serpa G, Raske C, Willemsen R, Hagerman PJ, Bagni C. Differential usage of transcriptional start sites and polyadenylation sites in FMR1 premutation alleles. Nucleic Acids Res. 2011 Aug;39(14):6172-85. doi: 10.1093/nar/gkr100. Epub 2011 Apr 7. PubMed PMID: 21478165; PubMed Central PMCID: PMC3152321.

Fazi B, Melino S, De Rubeis S, Bagni C, Paci M, Piacentini M, Di Sano F. Acetylation of RTN-1C regulates the induction of ER stress by the inhibition of HDAC activity in neuroectodermal tumors. Oncogene. 2009 Oct 29;28(43):3814-24. doi: 10.1038/onc.2009.233. Epub 2009 Aug 10. PubMed PMID: 19668229.

Napoli I, Mercaldo V, Boyl PP, Eleuteri B, Zalfa F, De Rubeis S, Di Marino D, Mohr E, Massimi M, Falconi M, Witke W, Costa-Mattioli M, Sonenberg N, Achsel T, Bagni C. The fragile X syndrome protein represses activity-dependent translation through CYFIP1, a new 4E-BP. Cell. 2008 Sep 19;134(6):1042-54. doi: 10.1016/j.cell.2008.07.031. PubMed PMID: 18805096.

Zalfa F, Eleuteri B, Dickson KS, Mercaldo V, De Rubeis S, di Penta A, Tabolacci E, Chiurazzi P, Neri G, Grant SG, Bagni C. A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci. 2007 May;10(5):578-87. doi: 10.1038/nn1893. Epub 2007 Apr 8. PubMed PMID: 17417632; PubMed Central PMCID: PMC2804293.

News

Congrats Adele on being one of the 2021 Uplifting Athletes Draft awardees!

Congrats Dr. De Rubeis for receiving a 2021 Distinguished Scholar Award!

Congrats Marta for receiving a fellowship from Fundación Alfonso Martín Escudero!

Congrats Dr. De Rubeis for the 2020 FBI Scholar Award with Dr. Zhuhao Wu!

Congrats to Dr. De Rubeis for receiving her first NIH grant to work on DDX3X syndrome!

Current Openings 

Funding

Beatrice & Samuel Seaver Foundation

NIH/NICHD 

Mindich Child Health and Development Institute

Icahn School of Medicine at Mount Sinai

Friedman Brain Institute

Fundación Alfonso Martín Escudero to Marta Garcia-Forn

New York University Dean’s Undergraduate Fund to Michael Flores

Fondation pour la Recherche Medicale to Devina Ung

Phillips Foundation to Devina Ung

Location
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

Education
Faculty Resources
Student Resources