My scientific research interests are in the field of neurosciences of emotion-cognition and neurobiology of “cognitive” disorders. I focus my research in genetic neurological disorders of cognitive impairment and in the study of the molecular basis of cognition.
Our research combines state-of-the-art genetic mouse models and behavioral paradigms combined with stereotaxic and pharmacology tools to explore in vivo brain function. Furthermore, a wide range of molecular tools and cell culture methods are employed.
Rett syndrome (RTT) is an autism spectrum neurodevelopmental disorder that affects mainly girls and is the second most prevalent form of intellectual disability in females. RTT intellectual disability is thought to result from changes in neuronal architecture including poor dendritic arborization and abnormal spine morphogenesis as well as impaired synaptic plasticity. Sporadic mutations (mostly) in the methyl-CpG binding protein 2 gene (MECP2) were identified as the molecular cause of RTT. The gene encodes for MeCP2, a protein known to regulate gene transcription through a myriad of mechanisms.
We focus in RTT intellectual disability and the underlying neuronal architecture abnormalities and we aim to 1) explore new molecular and epigenetic mechanisms underlying these changes and 2) dissect the contribution of the different RTT mutations to intellectual disability.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects mainly men, presenting with progressive development of tremors, ataxia and neuropsychological problems (memory impairment and dementia). FXTAS is caused by an expansion of the CGG repeat in the premutation range (between 55-200 repeats) of the FMR1 gene.
Our group uses a newly generated genetic mouse model that expresses a 90CGG repeat in an doxycycline-inducible system 1) to characterize critical time windows in the development and establishment of FXTAS (development vs. adult) and 2) to explore deeper the clinical spectrum of the CGG premutation focusing on cognition-related features.
B.Sc. in Biology, Faculty of Sciences, University of Porto, Portugal 2000
Ph.D. in Biomedical Sciences, Institute of Biomedical Sciences Abel Salazar, University of Porto, Portugal 2007
Postdoc, Center for Genomic Regulation, Barcelona, Spain 2008-2013
Telephone: +49(391)-67 55108
Emre Kul, M.Sc.
Foote M, Arque G, Berman RF, Santos M. Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) motor dysfunction modeled in mice. Cerebellum. 2016 Oct;15(5):611-22.
D’Amico D, Gener T, de Lagrán MM, Sanchez-Vives MV, Santos M, Dierssen M. Infralimbic Neurotrophin-3 infusion rescues fear extinction impairment in a mouse model of pathological fear. Neuropsychopharmacology. 2016 Sep 21
Bofill-De Ros X, Santos M, Vila-Casadesús M, Villanueva E, Andreu N, Dierssen M, Fillat C. Genome-wide miR-155 and miR-802 target gene identification in the hippocampus of Ts65Dn Down syndrome mouse model by miRNA sponges. BMC Genomics 2015 16(1), 907.
Santos M, D’Amico D, Dierssen M. From neural to genetic substrates of panic disorder: insights from human and mouse studies Eur J Pharmacol 2015.
Fillat C, Bofill-De Ros X, Santos M, Martín ED, Andreu N, Villanueva E, D’Amico D, Dierssen M, Altafaj X. Identification of key genes involved in Down syndrome pathogenesis by gene therapy. Rev Med Int Sínd Down 2014 18(2): 19-20.
Santos M, D’Amico D, Spadoni O, Amador-Arjona A, Dierssen M. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mousse model. J Neuroscience 2013 Sep 18; 33(38): 15259-71.
Temudo T, Santos M, Ramos E, Dias K, Vieira JP, Moreira A, Calado E, Carrilho I, Oliveira G, Levy A, Barbot C, Fonseca M, Cabral A, Cabral P, Monteiro J, Borges L, Gomes R, Mira G, Aires Pereira S, Santos M, Fernandes A, Epplen JT, Sequeiros J, Maciel P. Rett syndrome with and without detected MECP2 mutations: An attempt to redefine phenotypes. Brain Dev 2011 33(1): 69-76.
Santos M, Summavielle T, Teixeira S, Teixeira-Castro A, Silva-Fernandes A, Sousa N, Maciel P. Age- and region-specific analysis of monoaminergic systems in the brain of Mecp2 knock out mice implicates the prefrontal and motor cortices in the earliest stages of Rett syndrome. Neuroscience 2010 170(2): 453-67.
Santos M, Temudo T, Kay T, Carrilho I, Gaspar I, Barbot C, Medeira A, Cabral H, , Gomes R, Lourenço MT, Venâncio M, Calado E, Moreira A, Oliveira G and Maciel P. Mutations in the MECP2 gene are not a major cause of Rett-like phenotype in male patients. J Child Neurol 2009 24(1): 49-55.
Santos M, Yan J, Temudo T, Oliveira G, Vieira JP, Fen J, Sommer S and Maciel P. Analysis of highly conserved regions of the 3’ UTR of the MECP2 gene in patients with clinical diagnosis of Rett syndrome and mental retardation. Dis Markers 2008 24(6):319-324.
Ferro A, Castro MJ, Lemos C, Santos M, Sousa A, Pereira-Monteiro J, Sequeiros J, Maciel P. The C677T polymorphism in MTHFR is not associated with migraine in Portugal. Dis Markers 2008 25(2):107-113.
Carvalho A, Santos M, Maciel P and Rodrigues F. T-1237C polymorphism of TLR9 gene is not associated with multiple sclerosis in the Portuguese population. Multiple Sclerosis 2008 14(4):550-552.
Venâncio M, Santos M, Pereira SA, Maciel P, Saraiva. An explanation for another familial case of Rett syndrome: maternal germline mosaicism. Eur J Hum Genet. 2007 15(8):902-4.
Coutinho AM, Oliveira G, Katz C, Feng J, Yan J, Yang C, Marques C, Ataíde A, Miguel TS, Temudo T, Santos M, Maciel P, Sommer SS and Vicente AM. MECP2 coding sequence and 3’UTR variation in 172 unrelated autistic patients. Am J Med Genet – Part B Neuropsychiatr Genet 2007 144(4): 475-83.
Temudo T, Oliveira P, Santos M, Dias K, Vieira JP, Moreira A, Calado E, Carrilho I, Oliveira G, Levy A, Barbot C, Fonseca MJ, Cabral A, Dias A, Lobo Antunes N, Cabral P, Monteiro JP, Borges L, Gomes R, Barbosa C, Santos M, Mira G, Andrada G, Freitas P, Figueiroa S, Sequeiros J and Maciel P. Stereotypies in Rett Syndrome: analysis of 83 patients with and without detected MECP2 mutations. Neurology 2007 60(15):1183-7.
Santos M, Silva-Fernandes A, Oliveira P, Sousa N and Maciel P. Evidence for abnormal early development in a mouse model of Rett syndrome. Genes Brain & Behavior, 2007 6(3): 277-86.
Santos M, Coelho PA, Maciel P. Chromatin remodelling and neuronal function: exciting links. Genes Brain & Behavior 2006 5(suppl. 2):80-91.
The GAMES Collaborative Group (Santos M). Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans. J Neuroimmunol 2006 179:108-116.
Burwick R, Ramsay P, Haines J, Hauser S, Oksenberg M, Pericak-Vance M, Schmidt S, Compston A, Sawcer S, Cittadella R, Savettieri G Quattrone A, Polman C, Uitdehaag B, Zwemmer J, Hawkins C, Ollier W, Weatherby S, Enzinger C, Fazekas F, Schmidt H, Schmidt R, Hillert J, Thomas Masterman T, Hogh P, Niino M, Kikuchi S, Maciel P, Santos M, Rio ME, Kwiecinski H, akrzewska-Pniewska B, Evangelou N, Palace J, Barcellos L. APOE epsilon variation in multiple sclerosis susceptibility and disease severity: some answers. Neurology 2006 66: 1373-1383.
Shi J, Shibayama A, Liu Q, Nguyen VQ, Feng J, Santos M, Temudo T, Maciel P, Sommer SS. Detection of heterozygous deletions and duplications in the MECP2 gene in Rett syndrome by Robust Dosage PCR (RD-PCR). Hum Mutat 2005 25(5):505.
Santos M, Costa MC, Rio ME, Sá MJ, Monteiro MC, Valença A, Sá A, Dinis J, Figueiredo J, Almeida LB, Valongueiro A, Coelho I, Pinto-Basto J, Matamá MT, Sequeiros J, Maciel P. Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin. Mult Scler 2004 10(2): 153-7.
Santos M, Pinto-Basto J, Rio ME, Sá MJ, Valença A, Sá A, Dinis J, Figueiredo J, Bigotte de Almeida L, Coelho I, Sawcer S, Setakis E, Compston A, Sequeiros J, Maciel P. A whole genome screen for association with multiple sclerosis in Portuguese patients. J Neuroimmunol 2003 143 (1-2): 112-5.