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.

Dietary macronutrient composition impacts gene regulation in adipose tissue.
Dietary macronutrient composition impacts gene regulation in adipose tissue. Commun Biol. 2024 Feb 16; 7(1):194.
PMID: 38365885

Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells.
Mechanosensitive super-enhancers regulate genes linked to atherosclerosis in endothelial cells. J Cell Biol. 2024 Mar 04; 223(3).
PMID: 38231044

Splicing across adipocyte differentiation is highly dynamic and impacted by metabolic phenotype.
Splicing across adipocyte differentiation is highly dynamic and impacted by metabolic phenotype. Res Sq. 2023 Oct 31.
PMID: 37961160

A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes.
A non-coding variant linked to metabolic obesity with normal weight affects actin remodelling in subcutaneous adipocytes. Nat Metab. 2023 05; 5(5):861-879.
PMID: 37253881

Single cell profiling at the maternal-fetal interface reveals a deficiency of PD-L1+?non-immune cells in human spontaneous preterm labor.
Single cell profiling at the maternal-fetal interface reveals a deficiency of PD-L1+?non-immune cells in human spontaneous preterm labor. Sci Rep. 2023 05 16; 13(1):7903.
PMID: 37193763

Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing.
Upregulation of SYNGAP1 expression in mice and human neurons by redirecting alternative splicing. Neuron. 2023 05 17; 111(10):1637-1650.e5.
PMID: 36917980

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.
African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans. Genome Med. 2022 09 29; 14(1):112.
PMID: 36175932

Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women.
Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women. Alzheimers Dement. 2022 Jun 30.
PMID: 35770850

Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.
Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries. Circ Res. 2022 01 21; 130(2):166-180.
PMID: 34886679

Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts.
Establishment of human induced trophoblast stem-like cells from term villous cytotrophoblasts. Stem Cell Res. 2021 10; 56:102507.
PMID: 34454392

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