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.

Paternal dietary macronutrients affect the seminal vesicle fluid proteome and fetal development: a geometric framework for nutrition study in mice.
Paternal dietary macronutrients affect the seminal vesicle fluid proteome and fetal development: a geometric framework for nutrition study in mice. Proc Biol Sci. 2026 06 17; 293(2073).
PMID: 42336377

Negative regulation of human IL-33 in endothelium during allergic airway inflammation.
Negative regulation of human IL-33 in endothelium during allergic airway inflammation. JCI Insight. 2026 05 08; 11(9).
PMID: 42100869

Ancestry-informative regulatory variants at KCNB1 modulate adipogenesis and body mass index.
Ancestry-informative regulatory variants at KCNB1 modulate adipogenesis and body mass index. Front Endocrinol (Lausanne). 2026; 17:1805824.
PMID: 42181176

Splicing across adipocyte differentiation is highly dynamic and impacted by the metabolic phenotype.
Splicing across adipocyte differentiation is highly dynamic and impacted by the metabolic phenotype. iScience. 2025 Dec 19; 28(12):114119.
PMID: 41488358

Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring.
Dietary macronutrients modulate the proteome of brown adipose tissue in males and their female offspring. Cell Rep. 2025 Aug 26; 44(8):116050.
PMID: 40714632

Integration of functional genomics and statistical fine-mapping systematically characterizes adult-onset and childhood-onset asthma genetic associations.
Integration of functional genomics and statistical fine-mapping systematically characterizes adult-onset and childhood-onset asthma genetic associations. Genome Med. 2025 04 10; 17(1):35.
PMID: 40205616

Paternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring.
Paternal dietary macronutrient balance and energy intake drive metabolic and behavioral differences among offspring. Nat Commun. 2024 Apr 06; 15(1):2982.
PMID: 38582785

Dietary macronutrient composition impacts gene regulation in adipose tissue.
Dietary macronutrient composition impacts gene regulation in adipose tissue. Commun Biol. 2024 02 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 03 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

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