Marcelo A. Nobrega, MD PhD

We are interested in mechanistically deciphering how genetic variation increase the risk of human diseases. We are particularly interested in understanding how noncoding genetic variants, most uncovered by Genome-wide Association Studies are associated with disease etiology. The underlying assumption is that a majority of these variants impart their effects by altering the quantitative, temporal, and/or spatial properties of long-range cis-regulatory enhancers. Several challenges hinder the mechanistically follow-up of these GWAS, including 1) identification of the causal variant(s) associated with the disease trait, 2) characterization of the spatial and temporal properties of the enhancer(s) harboring the causal variant(s), 3) establishing differential regulatory properties of the allelic variants of the enhancer(s), 4) identification of the causal gene(s) connected with the enhancer(s) of interest, and 5) characterization of the molecular, cellular, and systems-level phenotypes associated with mis-regulation of the target gene(s). Our lab has been developing pipelines to tackle all these challenges, resulting in integrated experimental and computational strategies to uncover the mechanisms linking regulatory variants to human disease.

Identification of atrial fibrillation associated genes and functional non-coding variants.
van Ouwerkerk AF, Bosada FM, van Duijvenboden K, Hill MC, Montefiori LE, Scholman KT, Liu J, de Vries AAF, Boukens BJ, Ellinor PT, Goumans MJTH, Efimov IR, Nobrega MA, Barnett P, Martin JF, Christoffels VM. Identification of atrial fibrillation associated genes and functional non-coding variants. Nat Commun. 2019 Oct 18; 10(1):4755.
PMID: 31628324

TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia.
Srivastava R, Rolyan H, Xie Y, Li N, Bhat N, Hong L, Esteghamat F, Adeniran A, Geirsson A, Zhang J, Ge G, Nobrega M, Martin KA, Mani A. TCF7L2 (Transcription Factor 7-Like 2) Regulation of GATA6 (GATA-Binding Protein 6)-Dependent and -Independent Vascular Smooth Muscle Cell Plasticity and Intimal Hyperplasia. Arterioscler Thromb Vasc Biol. 2019 02; 39(2):250-262.
PMID: 30567484

Gene therapy for pathologic gene expression.
Montefiori LE, Nobrega MA. Gene therapy for pathologic gene expression. Science. 2019 01 18; 363(6424):231-232.
PMID: 30655431

Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development.
Boogerd CJ, Zhu X, Aneas I, Sakabe N, Zhang L, Sobreira DR, Montefiori L, Bogomolovas J, Joslin AC, Zhou B, Chen J, Nobrega MA, Evans SM. Tbx20 Is Required in Mid-Gestation Cardiomyocytes and Plays a Central Role in Atrial Development. Circ Res. 2018 08 03; 123(4):428-442.
PMID: 29903739

A promoter interaction map for cardiovascular disease genetics.
Montefiori LE, Sobreira DR, Sakabe NJ, Aneas I, Joslin AC, Hansen GT, Bozek G, Moskowitz IP, McNally EM, Nóbrega MA. A promoter interaction map for cardiovascular disease genetics. Elife. 2018 07 10; 7.
PMID: 29988018

Reducing mitochondrial reads in ATAC-seq using CRISPR/Cas9.
Montefiori L, Hernandez L, Zhang Z, Gilad Y, Ober C, Crawford G, Nobrega M, Jo Sakabe N. Reducing mitochondrial reads in ATAC-seq using CRISPR/Cas9. Sci Rep. 2017 05 26; 7(1):2451.
PMID: 28550296

DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Nicodemus-Johnson J, Myers RA, Sakabe NJ, Sobreira DR, Hogarth DK, Naureckas ET, Sperling AI, Solway J, White SR, Nobrega MA, Nicolae DL, Gilad Y, Ober C. DNA methylation in lung cells is associated with asthma endotypes and genetic risk. JCI Insight. 2016 12 08; 1(20):e90151.
PMID: 27942592

Editorial.
Nóbrega MA, Gómez-Skarmeta JL. Editorial. Semin Cell Dev Biol. 2016 09; 57:1.
PMID: 27499506

Probing chromatin landscape reveals roles of endocardial TBX20 in septation.
Boogerd CJ, Aneas I, Sakabe N, Dirschinger RJ, Cheng QJ, Zhou B, Chen J, Nobrega MA, Evans SM. Probing chromatin landscape reveals roles of endocardial TBX20 in septation. J Clin Invest. 2016 08 01; 126(8):3023-35.
PMID: 27348591

Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders.
Gómez-Marín C, Tena JJ, Acemel RD, López-Mayorga M, Naranjo S, de la Calle-Mustienes E, Maeso I, Beccari L, Aneas I, Vielmas E, Bovolenta P, Nobrega MA, Carvajal J, Gómez-Skarmeta JL. Evolutionary comparison reveals that diverging CTCF sites are signatures of ancestral topological associating domains borders. Proc Natl Acad Sci U S A. 2015 Jun 16; 112(24):7542-7.
PMID: 26034287

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