Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Coronary Artery Disease: HELP
Articles by Sylvia T. Nurnberg
Based on 4 articles published since 2008
||||

Between 2008 and 2019, Sylvia Nürnberg wrote the following 4 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
1 Review From Loci to Biology: Functional Genomics of Genome-Wide Association for Coronary Disease. 2016

Nurnberg, Sylvia T / Zhang, Hanrui / Hand, Nicholas J / Bauer, Robert C / Saleheen, Danish / Reilly, Muredach P / Rader, Daniel J. ·From the Division of Translational Medicine and Human Genetics, Department of Medicine (S.T.N., R.C.B., D.J.R.), Penn Cardiovascular Institute, Department of Medicine (H.Z., M.P.R., D.J.R.), Department of Genetics (N.J.H., D.J.R.), and Department of Biostatistics and Epidemiology (D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia. · From the Division of Translational Medicine and Human Genetics, Department of Medicine (S.T.N., R.C.B., D.J.R.), Penn Cardiovascular Institute, Department of Medicine (H.Z., M.P.R., D.J.R.), Department of Genetics (N.J.H., D.J.R.), and Department of Biostatistics and Epidemiology (D.S.), Perelman School of Medicine, University of Pennsylvania, Philadelphia. mpr2144@cumc.columbia.edu rader@upenn.edu. ·Circ Res · Pubmed #26892960.

ABSTRACT: Genome-wide association studies have provided a rich collection of ≈ 58 coronary artery disease (CAD) loci that suggest the existence of previously unsuspected new biology relevant to atherosclerosis. However, these studies only identify genomic loci associated with CAD, and many questions remain even after a genomic locus is definitively implicated, including the nature of the causal variant(s) and the causal gene(s), as well as the directionality of effect. There are several tools that can be used for investigation of the functional genomics of these loci, and progress has been made on a limited number of novel CAD loci. New biology regarding atherosclerosis and CAD will be learned through the functional genomics of these loci, and the hope is that at least some of these new pathways relevant to CAD pathogenesis will yield new therapeutic targets for the prevention and treatment of CAD.

2 Article Genetic Regulatory Mechanisms of Smooth Muscle Cells Map to Coronary Artery Disease Risk Loci. 2018

Liu, Boxiang / Pjanic, Milos / Wang, Ting / Nguyen, Trieu / Gloudemans, Michael / Rao, Abhiram / Castano, Victor G / Nurnberg, Sylvia / Rader, Daniel J / Elwyn, Susannah / Ingelsson, Erik / Montgomery, Stephen B / Miller, Clint L / Quertermous, Thomas. ·Department of Biology, School of Humanities and Sciences, Stanford University, Stanford, CA 94305, USA; Cardiovascular Institute, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. · Cardiovascular Institute, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Medicine, Stanford University, Stanford, CA 94305, USA. · Cardiovascular Institute, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. · Biomedical Informatics Training Program, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA. · Cardiovascular Institute, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA. · Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. · Cardiovascular Institute, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Pathology, Stanford University, Stanford, CA 94305, USA. · Center for Public Health Genomics, Department of Public Health Sciences, Biochemistry and Genetics, and Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA. · Cardiovascular Institute, Stanford School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Medicine, Stanford University, Stanford, CA 94305, USA. Electronic address: tomq1@stanford.edu. ·Am J Hum Genet · Pubmed #30146127.

ABSTRACT: Coronary artery disease (CAD) is the leading cause of death globally. Genome-wide association studies (GWASs) have identified more than 95 independent loci that influence CAD risk, most of which reside in non-coding regions of the genome. To interpret these loci, we generated transcriptome and whole-genome datasets using human coronary artery smooth muscle cells (HCASMCs) from 52 unrelated donors, as well as epigenomic datasets using ATAC-seq on a subset of 8 donors. Through systematic comparison with publicly available datasets from GTEx and ENCODE projects, we identified transcriptomic, epigenetic, and genetic regulatory mechanisms specific to HCASMCs. We assessed the relevance of HCASMCs to CAD risk using transcriptomic and epigenomic level analyses. By jointly modeling eQTL and GWAS datasets, we identified five genes (SIPA1, TCF21, SMAD3, FES, and PDGFRA) that may modulate CAD risk through HCASMCs, all of which have relevant functional roles in vascular remodeling. Comparison with GTEx data suggests that SIPA1 and PDGFRA influence CAD risk predominantly through HCASMCs, while other annotated genes may have multiple cell and tissue targets. Together, these results provide tissue-specific and mechanistic insights into the regulation of a critical vascular cell type associated with CAD in human populations.

3 Article Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap. 2015

Nurnberg, Sylvia T / Cheng, Karen / Raiesdana, Azad / Kundu, Ramendra / Miller, Clint L / Kim, Juyong B / Arora, Komal / Carcamo-Oribe, Ivan / Xiong, Yiqin / Tellakula, Nikhil / Nanda, Vivek / Murthy, Nikitha / Boisvert, William A / Hedin, Ulf / Perisic, Ljubica / Aldi, Silvia / Maegdefessel, Lars / Pjanic, Milos / Owens, Gary K / Tallquist, Michelle D / Quertermous, Thomas. ·Department of Medicine, Cardiovascular Research Institute, Stanford University School of Medicine, Stanford, California, United States of America. · Department of Medicine, University of Hawaii, Honolulu, Hawaii, United States of America. · Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. · Department of Medicine, Karolinska Institute, Stockholm, Sweden. · Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia, United States of America. ·PLoS Genet · Pubmed #26020946.

ABSTRACT: Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including "vascular disease," "disorder of artery," and "occlusion of artery," as well as disease-related cellular functions including "cellular movement" and "cellular growth and proliferation." In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.

4 Article Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci. 2015

Sazonova, Olga / Zhao, Yuqi / Nürnberg, Sylvia / Miller, Clint / Pjanic, Milos / Castano, Victor G / Kim, Juyong B / Salfati, Elias L / Kundaje, Anshul B / Bejerano, Gill / Assimes, Themistocles / Yang, Xia / Quertermous, Thomas. ·Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America; Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States of America. · Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, California, United States of America. · Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, United States of America. · Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America. · Cardiovascular Institute, Stanford University School of Medicine, Stanford, California, United States of America; Department of Computer Science, Stanford University School of Medicine, Stanford, California, United States of America; Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America; Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America. ·PLoS Genet · Pubmed #26020271.

ABSTRACT: To functionally link coronary artery disease (CAD) causal genes identified by genome wide association studies (GWAS), and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq) with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC). Analysis of identified TCF21 target genes for enrichment of molecular and cellular annotation terms identified processes relevant to CAD pathophysiology, including "growth factor binding," "matrix interaction," and "smooth muscle contraction." We characterized the canonical binding sequence for TCF21 as CAGCTG, identified AP-1 binding sites in TCF21 peaks, and by conducting ChIP-Seq for JUN and JUND in HCASMC confirmed that there is significant overlap between TCF21 and AP-1 binding loci in this cell type. Expression quantitative trait variation mapped to target genes of TCF21 was significantly enriched among variants with low P-values in the GWAS analyses, suggesting a possible functional interaction between TCF21 binding and causal variants in other CAD disease loci. Separate enrichment analyses found over-representation of TCF21 target genes among CAD associated genes, and linkage disequilibrium between TCF21 peak variation and that found in GWAS loci, consistent with the hypothesis that TCF21 may affect disease risk through interaction with other disease associated loci. Interestingly, enrichment for TCF21 target genes was also found among other genome wide association phenotypes, including height and inflammatory bowel disease, suggesting a functional profile important for basic cellular processes in non-vascular tissues. Thus, data and analyses presented here suggest that study of GWAS transcription factors may be a highly useful approach to identifying disease gene interactions and thus pathways that may be relevant to complex disease etiology.