Dierssen Lab
Systems and Synthetic Biology
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1989 Ph.D. Department of Physiology and Pharmacology, Universidad de Cantabria (Spain).
1990-1993 Postdoctoral work at the Universidad Autònoma de Barcelona (Spain).
1993-1997 Assistant Professor at the Universidad de Cantabria (Spain).
1997-2001 Research position. Medical and Molecular Genetics Center-Institut de Recerca Oncológica (IRO), Barcelona (Spain).
2001-Present Group Leader at the Center for Genomic Regulation, Barcelona (Spain).
Group news
UAB Social Council awards Mara Dierssen for her research in the field of Down Syndrome (18/12/2020)
Mara Dierssen awarded the “Optimistas Comprometidos” Prize (10/05/2018)
Mara Dierssen awarded the Big Vang Medal (16/06/2017)
Mara Dierssen receives the Trifermed award (09/06/2017)
Mara Dierssen elected president Trisomy 21 Society (11/11/2016)
Mara Dierssen Distinguished Alumni of the University of Cantabria (18/06/2015)
Facial development in Down syndrome and green tea extracts (04/03/2021)
The intake of green tea extracts potentially reduces facial dysmorphology in children with Down syndrome
International study finds increased mortality in adults with Down syndrome (22/02/2021)
Findings reiterate need to prioritise vaccinations for those with the genetic disorder
People with Down syndrome are genetically susceptible to COVID-19 (09/02/2021)
A study by researchers at the Centre for Genomic Regulation (CRG) reveals the genetic factors that may expose or protect people with Down syndrome from SARS-CoV-2 infection, as well as the prognosis of COVID-19.
€1.97 million to develop a treatment for fragile X syndrome (01/12/2020)
The project brings together a multidisciplinary team with in-depth knowledge of intellectual disability
Potential Down’s syndrome treatment may improve cognition through epigenetic activity in brain (29/09/2020)
CRG researchers describe some of the mechanisms underlying the potential beneficial effects of a new treatment
New therapeutic targets for treating memory impairment in Down syndrome (05/05/2020)
New research reveals how the genes in our brain change with what we eat (28/02/2019)
The study shows that small changes in the expression of many genes correlate with physical and behavioural changes in the mice
Major international project aims to identify causes of dementia (18/12/2018)
European scientists have launched a research programme, which aims to identify common causes of dementia in Alzheimer’s Disease, Parkinson’s Disease and Down Syndrome.
Binge-eating mice reveal obesity clues (09/04/2018)
Mice fed on a high fat or chocolate-based diet show abnormal feeding behaviours such as snacking, bingeing and disrupted eating patterns, according to new research from scientists at the Centre for Genomic Regulation (CRG) and the Pompeu Fabra University (UPF) in Barcelona, Spain. The findings of two studies published back-to-back in the journal Addiction Biology help to explain the behavioural triggers leading to obesity and point towards new ideas for preventing weight gain.
Dierssen lab publishes translational research discovering a pro-cognitive therapy for Down syndrome in Lancet Neurology (07/06/2016)
New research published in Lancet Neurology has found using a inhibitor of DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase DYRK1A), a serine/threonine kinase involved in brain plasticity, in combination with cognitive training improves some measures of cognition and behavior in subjects with Down syndrome.
Gene Linked to Down Syndrome Associated With Altered Oscillations in Cerebral Cortex (05/04/2016)
Scientists at the CRG and IDIBAPS in Barcelona, Spain, have made a first-ever identification of the alterations in the neuronal circuit that impact cerebral cortex physiology.
The Institució CERCA launches a video that walks you through several types of conversation in a mock evaluation panel that hinder objectivity towards candidates
The CERCA centers diversity commission, chaired by Mara Dierssen has drawn up a pioneering tool to inform faculty, both men and women, that shows bias in evaluation, which is particularly detrimental to women.
Summary
The Dierssen lab is centered on understanding cognition and behavior and their perturbation in intellectual disability. Our main question is:
What are the changes in neuronal architecture and connectivity that disrupt cortical and hippocampal function, in genetic cognitive disorders? In other words, what is the multi-scale link from molecular alterations to impaired cognition and behavior?
We are an interdisciplinary team of physicists, bioinformaticians and experimental biologists, and we focus on data collection (behavior, 3D imaging, genomic data) of many variables of the system (longitudinal behavioral analysis, population based analysis in neuronal networks, gene expression patterns). We take advantage of computer modeling and bioinformatics analysis (gene networks, neuronal network modeling, etc.) to tackling classical unresolved questions in the field, such as: (a) pathological disturbances of structural optimality in single cell and neuronal networks, (b) genomic dependence of cognitive disturbances, (c) identification of predictive non-invasive biomarkers, (d) discovery of pro-cognitive therapies.
Other Activities
TEDxSantCugat - Mara Dierssen - La fuerza de la diferencia (in Spanish)
Brain Polyphony Concert 10 December 2016
Neuroscience Christmas Symposium 21 December 2016
International Master Degree in Neurosciences
TEDxSol - Mara Dierssen - Cómo podemos fabricar un entorno que cambie nuestro cerebro (in Spanish)
Funding acknowledgements
Title: Desarrollo de una terapia para el síndrome X Frágil
Eligible total cost: 179.962,80 €
Period: 01/01/2020 to 31/12/2023
Ref.: RTC2019-007230-1
Funding agency: National Research Agency (Agencia Estatal de Investigación, AEI), from the Spanish Ministry of Science and Innovation.
Title: Obtaining antioxidant active ingredients from the carob pod and validation of its therapeutic potential
Eligible total cost: 156.174,70 €
Period: 01/09/2020 to 31/12/2023
Ref.: RTC2019-007329-1
Funding agency: National Research Agency (Agencia Estatal de Investigación, AEI), from the Spanish Ministry of Science and Innovation.
Title: Engramas de memoria en el síndrome de Down: alteraciones celulares y moleculares ("Chasing the memory engrams and underlying cellular and molecular alterations in Down syndrome")
Eligible total cost: 321.860 €
Period: 01/06/2020 to 31/05/2023
Ref.: PID2019-110755RB-I00 / AEI / 10.13039/501100011033
Funding agency: National Research Agency (Agencia Estatal de Investigación, AEI), from the Spanish Ministry of Science and Innovation.

This project “Psych-STRATA - A Stratified Treatment Algorithm in Psychiatry: A program on stratified pharmacogenomics in severe mental illness” has received funding from the European Union’s HORIZON-HLTH-2021 program under grant agreement No 101057454.
Modeling micro-anatomical and dynamic properties of cognition-related brain systems
Funded by EU (JPND), MINECO, CRG, Jerôme Lejeune Foundation
The main focus of the project is to understand how genetic perturbation in mental disorders modifies the way the brain integrates information. Alterations in the architectural properties of the neurons are observed in most mental disorders and are assumed to be the cause of the cognitive disturbances. Thus, the main question in the field remains how these disturbances of neuronal architecture constrain the network and influence the flow and storage of information in neuronal circuits. We integrate experimental data from cleared brains with physiological and cellular quantitative measurements with computer modeling. To this aim we have developed a suite of unified tools specially designed for analyzing data from brain clearing methods including workflows for network connectivity instantiation and network dynamics simulation. Our first analysis in intellectual disability mouse models revealed that the dendritic tree architecture and the distribution of synaptic contacts have significant implications on information processing efficiency and storage capacity, and suggests that those single-neuron features permeate to the network level, determining the computational capacities of neural ensembles (Manubens et al in preparation). Using a conductance-based computational model, we demonstrated that selective disinhibition of fast-spiking interneurons could explain overinhibition and decreased gamma power and firing rate in cortical circuit, that might be central to the pathophysiology of Down syndrome (Ruiz-Mejías et al 2016). We also have described how subtle alterations in the activation pattern of amygdala-hippocampus-medial prefrontal cortex fear circuit produced increased fear memories in a panic disorder mouse model (Santos et al 2013, Damico et al 2017). This innovative and powerful analytical platform combined with in vivo systems (genetically modified mouse models) and human pathologies will help us understand the neurobiology of mental disorders and the effects on network topology of pro-cognitive treatments.
Ruiz-Mejias M, … Dierssen M. Overexpression of Dyrk1A, a Down Syndrome Candidate, Decreases Excitability and Impairs Gamma Oscillations in the Prefrontal Cortex. J Neurosci. (2016) 36(13):3648-59.
Pons-Espinal M, Martinez de Lagrán M, Dierssen M. Environmental enrichment rescues DYRK1A activity and hippocampal adult neurogenesis in TgDyrk1A.Neurobiol Dis. (2013) 60:18-31.
Santos M, … Dierssen M. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse model. J Neurosci. (2013) 18;33(38):15259-71.
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 (2017) 42(2): 462-472.
Exploring molecular mechanisms of pro-cognitive therapies
Funded by MINECO, CRG, Jerôme Lejeune Foundation
Down syndrome (DS) is the most frequent genetic cause of intellectual disability. It is a multifaceted condition characterized by impairments in cognition, communication, behavior and/or motor skills resulting from abnormal brain development and function. Although DS is caused by the trisomy with more than 300 triplicated genes located on chromosome 21, there are a reduced number of dosage-sensitive candidate genes that play a critical role in the pathogenesis of the disorder. Our group has made important contributions demonstrating that overexpression of DYRK1A, a DS candidate gene, is sufficient and necessary to recapitulate some of the DS phenotypes (Martinez de Lagrán et al, 2012, Dierssen et al 2012). Importantly, it is a druggable molecular target we could also demonstrate that the genetic, pharmacological or environmental normalization of its overdosage rescues behavioral, cognitive and neuronal phenotypes in preclinical studies with DS mouse models and in clinical trials in humans (de la Torre et al 2016). Specifically, it is involved in complex remodeling of neural circuitry in the hippocampus (Martinez de Lagran et al, 2012; Pons-Espinal et al, 2013). Importantly, we could also demonstrate that the genetic, pharmacological or environmental normalization of its overdosage, possibly along with effects at other levels (epigenetic, transcriptomic), rescues behavioral, cognitive and neuronal phenotypes in preclinical studies with DS mouse models and in clinical trials in humans (Dierssen, 2012). The triplication of DYRK1A, can lead to an epigenetic imbalance. DYRK1A interacts with the REST/NRSF-SWI/SNF chromatin-remodeling complex and regulates histone acetylation, therefore influencing gene expression. We are exploring proteomic alterations, transcriptome regulation and epigenomic modifications (De Toma et al., 2016) to decipher the most relevant mechanisms. The first proteomic studies have shown that the consequences of DYRK1A overexpression spread along plasticity-related molecular pathways (Ortega et al in preparation). This may explain why DYRK1A kinase normalization is a good molecular target in Down syndrome. Finally, we are interested in the common mechanisms underlying different intellectual disabilities. In fact, EGCG, the main polyphenol extracted from green tea, is able to restore the cognitive impairment in both Fragile X syndrome and Down syndrome (De la Torre et al, 2016, and De la Torre et al in preparation), despite the opposite defects at the neuronal level. We are studying the common transcriptomic pathways, which are altered in these two diseases. Interestingly, many genes involved in Down syndrome are also affected due to the lack of the FMRP protein in Fragile X syndrome (De Toma et al., 2016, De Toma et al in press).
de la Torre R, … Dierssen M. Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomized, placebo-controlled, phase 2 trial. Lancet Neurol. (2016) 15(8):801-810
Martinez de Lagran M, … Dierssen M. Dyrk1A influences neuronal morphogenesis through regulation of cytoskeletal dynamics in mammalian cortical neurons. Cereb Cortex. (2012) 22: 2867-77
Toma ID, Gil LM, Ossowski S, Dierssen M. Where Environment Meets Cognition: A Focus on Two Developmental Intellectual Disability Disorders. Neural Plast. (2016) 2016:4235898
Dierssen M. Down syndrome: the brain in trisomic mode. Nat Rev Neurosci. (2012) 13: 844-58.
High-throughput phenotypic cluster
Funded by EU (Era-Net), MINECO
Intellectual disabilities are frequently accompanied by behavioral disturbance. We have developed an experimental framework, including high-throughput longitudinal behavioral recording (Espinosa et al., 2018), and an open access software to visualize, integrate and analyze longitudinal big behavioral data (Pergola, Espinosa et al., in preparation). This allows the detection of subtle signs of behavioral disturbances that appear at an early stage of morbidity development. Among others, we have explored learning (Catuara et el, 2015) and obesity (Fructuoso et al, in preparation) phenotypes in intellectual disability disorders, focusing on Down syndrome. We found hat trisomy 21 leads to abnormal feeding behaviors and differential endocrine and neurochemical adaptations to an obesogenic environment (Fructuoso et al, 2018).
Espinosa-Carrasco J, … Dierssen M. Time-course and dynamics of obesity-related behavioral changes induced by energy-dense foods in mice. Addict Biol. (2018) Epub ahead of print
Fructuoso M, … Dierssen M. Increased levels of inflammatory plasma markers and obesity risk in a mouse model of Down syndrome. Free Radic Biol Med. (2018) 114:122-130
Catuara-Solarz S, Espinosa-Carrasco J, Erb I, Langohr K, Notredame C, Gonzalez JR, Dierssen M Principal Component Analysis of the Effects of Environmental Enrichment and (-)-epigallocatechin-3-gallate on Age-Associated Learning Deficits in a Mouse Model of Down Syndrome. Front Behav Neurosci. (2015) 9: 330.