Marcelo A. Nobrega

Research Summary
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.
Biosciences Graduate Program Association
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  2. 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. View in: PubMed

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  46. Appendage expression driven by the Hoxd Global Control Region is an ancient gnathostome feature. Proc Natl Acad Sci U S A. 2011 Aug 02; 108(31):12782-6. View in: PubMed

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  51. An 8q24 gene desert variant associated with prostate cancer risk confers differential in vivo activity to a MYC enhancer. Genome Res. 2010 Sep; 20(9):1191-7. View in: PubMed

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  56. Distinct genetic regulation of progression of diabetes and renal disease in the Goto-Kakizaki rat. Physiol Genomics. 2009 Sep 09; 39(1):38-46. View in: PubMed

  57. Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. J Med Genet. 2009 Aug; 46(8):511-23. View in: PubMed

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  59. Predicting tissue-specific enhancers in the human genome. Genome Res. 2007 Feb; 17(2):201-11. View in: PubMed

  60. In vivo enhancer analysis of human conserved non-coding sequences. Nature. 2006 Nov 23; 444(7118):499-502. View in: PubMed

  61. Identifying synonymous regulatory elements in vertebrate genomes. Nucleic Acids Res. 2005 Jul 01; 33(Web Server issue):W403-7. View in: PubMed

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  73. Transfer RNA genes in the cap-oxil region of yeast mitochondrial DNA. Nucleic Acids Res. 1980 Nov 11; 8(21):5017-30. View in: PubMed