De Rubeis lab

Research 

We study 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.

We are part of the Seaver Autism Center for Research and Treatment at the Icahn School of Medicine at Mount Sinai in 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.

We are currently focusing on two rare genetic disorders: DDX3X syndrome and ADNP syndrome.

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. In collaboration with Dr. Elodie Drapeau, we also generate human neurons carrying specific DDX3X mutations found in females and males with DDX3X syndrome. 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

Principal Investigator

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

Dr. De Rubeis is a neuroscientist and geneticist interested in understanding the genetic, molecular and cellular mechanisms underlying autism spectrum disorder (ASD) and intellectual disability (ID).

Dr. De Rubeis completed her bachelor, master and PhD degrees in Cellular and Molecular Biology at the University of Rome Tor Vergata in Rome, Italy. During her PhD and first postdoctoral training in Molecular Neuroscience with Dr. Claudia Bagni at the Katholieke Universiteit Leuven and Vlaams Instituut voor Biotechnologie (VIB) in Leuven, Belgium, she studied how the regulation of mRNA translation shapes the synaptic development in the context of Fragile X syndrome, a leading monogenic cause of ASD and the most common inherited form of ID. During this training, she visited the laboratory of Dr. Eric Klann at the New York University as an EMBO short-term fellow. She then joined the Icahn School of Medicine at Mount Sinai for a second postdoctoral training in Genetics and Genomics in the lab of Dr. Joseph Buxbaum. She studied the role of rare genetic variation in ASD through large-scale exome sequencing analyses and discovered novel genes and loci conferring risk. As part of that collaboration, she continues to lead efforts of a large-scale autism genomic consortium (Autism Sequencing Consortium).

Dr. De Rubeis’ research combines genetics, molecular biology, developmental biology and neuroscience to understand the pathophysiology of ASD and ID. Her team is currently focusing on two rare genetic neurodevelopmental disorders associated with ASD and ID: DDX3X syndrome and ADNP syndrome.

 

 

Dévina Ung, PhD | Postdoctoral Fellow

Dévina joined the lab in June 2018 after completing her PhD in Neurogenetics at the University of Tours, France, in the laboratory of Dr. Frederic Laumonnier. 

Dévina studies the role of DDX3X in the morphogenesis and synaptogenesis of cortical neurons using a novel mouse model of DDX3X syndrome. Her work aims at capturing the pathophysiology of DDX3X syndrome and developing novel treatments. To join the De Rubeis lab, she received a one-year fellowship from the Fondation pour la Recherche Médicale. Currently, she is supported by a two-year fellowship from the Beatrice & Samuel Seaver Foundation and by the Phillippe Foundation. 

After her postdoctoral training, she intends to establish an independent academic career focusing on the neurobiology of neurodevelopmental disorders. 

Marta Garcia-Forn, PhD | Postdoctoral Fellow

Marta joined the lab in January 2020 after completing her PhD in Biomedicine at the University of Barcelona, Spain, in the laboratory of Dr. Esther Perez-Navarro. While there, she studied nuclear and protein synthesis alterations occurring in the brain and peripheral tissues of Huntington’s disease patients and mouse models.

Marta studies the development and connectivity of glutamatergic projection neurons in the cortex of mice modeling DDX3X syndrome, and their relationship to behavioral deficits.

After her postdoctoral training, she intends to establish an independent academic career focusing on the neurobiology of neurological disorders.

Andrea Boitnott | Associate Researcher

Andrea joined the lab in July 2018 after graduating from Bates College with a Bachelor’s of Science in Neuroscience and a double minor in Chemistry and Educational Studies. While there, she conducted behavioral testing in a novel mouse model for a rare form of intellectual disability, Pitt-Hopkins syndrome, in the laboratory of Dr. Andrew Kennedy. 

Andrea is working on characterizing a mouse model of DDX3X syndrome, by following mice throughout development and adulthood. 

After the two years in the De Rubeis lab, Andrea intends to pursue a PhD in neuroscience.

Danielle Mendonca | Associate Researcher

Danielle joined the lab in June 2018 after graduating from New York University in January 2018 with a degree in Neural Science. While there, she studied the expression of synaptic glutamatergic receptors in a mouse model for anorexia nervosa, in the laboratory of Dr. Chiye Aoki.

Danielle studies the molecular complexes and mRNA targets of DDX3X. She also works on the identification of blood-based biomarkers in ADNP syndrome. 

After the two years in the De Rubeis lab, Danielle intends to pursue a career in medicine.

Kristi Niblo | Associate Researcher

Kristi received a Bachelor’s of Science in Veterinary Technology from Mercy College. While there, she interned at Regeneron Pharmaceuticals where she rotated in multiple labs studying animal models of ophthalmologic and cardiac diseases and atopic dermatitis. It was at this internship where she discovered her interest in scientific research and decided to combine this with her passion for veterinary medicine. She gained New York State licensing as a Veterinary Technologist in 2017 before joining the Seaver Autism Center and is currently pursuing a Surgical Research Specialist certification.

At the De Rubeis lab, Kristi oversees the colonies of transgenic mouse models of DDX3X syndrome and she helped set up the initial characterization of the DDX3X mouse model. 

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 Andrea’s supervision, Michael is working on the role of DDX3X on corticogenesis and synaptogenesis using the mouse model of DDX3X syndrome. 

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.  
 

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

Rona Yu | Research Intern

Rona is a research volunteer in the De Rubeis lab, where she is helping characterize a mouse model of DDX3X syndrome.
 
She is a rising undergraduate senior in Computer Science at Caltech, where she assists with fMRI operation and data analysis with Dr. Ralph Adolphs. Outside research, Rona also serves as the Co-President of her school’s Engineers Without Borders chapter, an Upper Class Counselor, and a Title IX Advocate. 

Alumni

Ariela Buxbaum Grice
Francois Muratet
Rocio Villena
Amanda de Favre Noguera

Collaborators

Publications

2020

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. [Epub ahead of print] PubMed 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.
[Epub ahead of print] PubMed 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

Congratulations to Dr. De Rubeis for receiving the 2020 Friedman Brain Institute Scholar Award with Dr. Zhuhao Wu!

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

Congratulations to Dévina for receiving the $12,000 grant for travel to and from France to support a Franco-American research exchange!

Andrea Boitnott presents her work on our novel DDX3X mouse model at the International Society for Autism Research (INSAR) 2019 Annual Meeting in Montréal, Canada.

Congratulations to Dévina for receiving the $12,000 grant for travel to and from France to support a Franco-American research exchange!

Congratulations to Rona for receiving a Thomas Hunt Morgan Caltech SURF fellowship!

Corticopontine connections: Retrograde labeling of corticaneurons projecting to the pons in the mouse brain. This technique uses viral particles that are comDepetent for retrograde transport. The viral particles are injected in the pons and transported to cortical neurons innervating the pons.

Dévina Ung presents her work on DDX3X syndrome at the International Society for Autism Research (INSAR) 2019 Annual Meeting in Montréal, Canada.

Danielle Mendonca presents her work on on DDX3X syndrome at Mount Sinai’s Child Health Research Day, April 2019. 

Dr. De Rubeis discusses her research in her Employee Spotlight interview.

Dr. De Rubeis and Dr. Buxbaum discuss research on a rare genetic disorder that informs autism and lead to better clinical care on this Facebook live.

Dr. De Rubeis featured in the Seaver Autism Center’s 25th Anniversary video. 

Current Openings 

Postdoctoral fellow

We are seeking an ambitious, creative, and motivated postdoctoral fellow – join us! More info here.

Research Associate

We are seeking an ambitious and motivated Research Associate – come work with us! More info here.

Funding

Beatrice & Samuel Seaver Foundation

NIH/NICHD 

Friedman Brain Institute Scholar Award

Fondation pour la Recherche Medicale (supporting Devina Ung, PhD)

Phillips Foundation (supporting Devina Ung, PhD)

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