A5011074610- Endoplasmic Reticulum Stress and Disease
- Atherosclerosis and Cardiovascular Diseases
- Liver Disease Diagnosis and Treatment
- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Single-cell and spatial transcriptomics
- Chronic Myeloid Leukemia Treatments
- Lipid metabolism and disorders
- Phagocytosis and Immune Regulation
- Genetic Associations and Epidemiology
- Chronic Lymphocytic Leukemia Research
- Pediatric Hepatobiliary Diseases and Treatments
- Effects of Radiation Exposure
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Cardiovascular Disease and Adiposity
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Wnt/β-catenin signaling in development and cancer
- Autophagy in Disease and Therapy
- Congenital heart defects research
- Galectins and Cancer Biology
- Gallbladder and Bile Duct Disorders
- Renin-Angiotensin System Studies
- Lymphoma Diagnosis and Treatment
Columbia University
2003-2024
Columbia University Irving Medical Center
2017-2024
Austrian Agency for Health and Food Safety
2024
A.T. Still University
2020-2022
Genomics (United Kingdom)
2021
National Institute of Diabetes and Digestive and Kidney Diseases
2021
National Institutes of Health
2021
Northwestern University
2021
Children's Hospital of Philadelphia
2010-2019
University of Pennsylvania
2011-2019
Rationale: Endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, transcriptional regulation of endothelial inflammation has not been well clarified. Objective: This study aims explore Foxp (forkhead box P) transcription factor 1 homeostasis, atherogenesis, its mechanisms. Methods Results: To assess the importance Foxp1 atherosclerosis, expression was analyzed human coronary artery mouse artery, we observed...
BACKGROUND: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture cells. However, our understanding the comprehensive transcriptional and phenotypic landscape cells within these lesions is limited. METHODS: To characterize human carotid atherosclerosis in greater detail, we combined cellular indexing transcriptomes epitopes by sequencing single-cell RNA to classify all cell types (n=21; 13 symptomatic) achieve multimodal identities their association with clinical...
<h3>Background</h3> Alagille syndrome (ALGS) is a dominant, multisystem disorder caused by mutations in the Jagged1 (JAG1) ligand 94% of patients, and NOTCH2 receptor <1%. There are only two families reported to date. This study hypothesised that additional <i>NOTCH2</i> would be present patients with clinical features ALGS without <i>JAG1</i> mutation. <h3>Methods</h3> The screened cohort <i>JAG1</i>-negative individuals suggestive or diagnostic for mutations. <h3>Results</h3> Eight...
Mutations in the Notch pathway ligand Jagged1 (JAG1) cause Alagille syndrome (AGS), as well cardiac defects seemingly nonsyndromic individuals. To estimate frequency of JAG1 mutations cases with right-sided not otherwise diagnosed AGS, we screened 94 tetralogy Fallot (TOF) and 50 pulmonic stenosis/peripheral pulmonary stenosis (PS/PPS) or valve atresia intact ventricular septum (PA) for mutations. Sequence changes were identified three TOF PS/PPS/PA patients, that present 100 controls. We...
Background— Genome-wide association studies have established ADAMTS7 as a locus for coronary artery disease in humans. However, these fail to provide directionality the between and disease. Previous reports implicated regulation of vascular smooth muscle cell migration, but role direction impact this gene atherogenesis not been shown relevant model systems. Methods Results— We bred an Adamts7 whole-body knockout mouse onto both Ldlr Apoe hyperlipidemic models. −/− / mice displayed...
Alagille syndrome is an autosomal dominant disease with a known molecular etiology of dysfunctional Notch signaling caused primarily by pathogenic variants in JAGGED1 (JAG1), but also NOTCH2. The majority JAG1 result loss function, however has been attributed to lesser understood missense variants. Conversely, the NOTCH2 are missense, though fewer these have described. In addition, there small group patients clear clinical phenotype absence variant. Here, we catalog our single-center study,...
Variants near the gene TRIB1 are significantly associated with several plasma lipid traits, circulating liver enzymes, and development of coronary artery disease in humans; however, it is not clear how its protein product tribbles-1 regulates metabolism. Here, we evaluated mice harboring a liver-specific deletion Trib1 (Trib1_LSKO) to elucidate role mammalian hepatic These exhibited increased triglyceride (TG) content, lipogenic transcription, de novo lipogenesis. Microarray analysis...
Objective— ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) cleaves von Willebrand factor, thereby modulating thrombosis inflammation. Low plasma activity is associated cardiovascular events, including myocardial cerebral infarction. Here, we investigated the role of in development early atherosclerosis a murine model. Methods Results— Apolipoprotein E–null (ApoE −/− ) Adamts13-null (Adamts13 ApoE mice were fed high-fat Western diet for 12 weeks....
Background: Common diseases such as coronary heart disease (CHD) are complex in etiology. The interaction of genetic susceptibility with lifestyle factors may play a prominent role. However, gene-lifestyle interactions for CHD have been difficult to identify. Here, we investigate smoking behavior, potent factor, genotypes that shown associate risk. Methods: We analyzed data on 60 919 cases and 80 243 controls from 29 studies gene-smoking variants at 45 loci previously reported be associated...
Deciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers regulatory elements genome, any specific modification has not been assayed in more than a few individuals liver. As result, effects states liver poorly understood. Here, we generate most comprehensive genome-wide dataset two epigenetic marks, H3K4me3 and H3K27ac, annotate thousands putative We integrate these...
Trib1 controls atherosclerotic plaque macrophage function by up-regulating OLR1, promoting foam cell formation and atherosclerosis.
To gain mechanistic insights into the role of LIPA (lipase A), gene encoding LAL (lysosomal acid lipase) protein, in human macrophages.We used CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) technology to knock out induced pluripotent stem cells and then differentiate macrophage (human-induced cells-derived [IPSDM]) explore loss-of-function phenotypes. was abundantly expressed monocyte-derived macrophages markedly on IPSDM differentiation...
Background: Vascular smooth muscle cells (VSMCs) play a central role in atherosclerosis by undergoing phenotypic modulation from quiescent, contractile state to range of synthetic phenotypes, including fibroblast-like, macrophage-like, and lipid-laden foam cell?like states. However, comprehensive multimodal characterization understanding the transcriptional programs driving these transitions remain incomplete. Methods: To comprehensively define diversity VSMCs during progression, we...
Obesity is associated with adipose tissue inflammation that contributes to insulin resistance. Zinc finger protein 36 (Zfp36) an mRNA-binding reduces by binding cytokine transcripts and promoting their degradation. We hypothesized myeloid-specific deficiency of Zfp36 would lead increased reduced sensitivity in diet-induced obese mice. As expected, wild-type (Control) mice became diabetic on a high-fat diet, loss [knockout (KO)] demonstrated liver mRNA expression compared Control...
Genetic variants near the TRIB1 gene are highly significantly associated with plasma lipid traits and coronary artery disease. While is likely causal of these associations, molecular mechanisms not well understood. Here we sought to investigate how influences low density lipoprotein cholesterol (LDL-C) levels in mice. Hepatocyte-specific deletion Trib1 (Trib1Δhep) mice increased apoB slowed catabolism LDL-apoB due decreased LDL receptor (LDLR) mRNA protein. Simultaneous transcription factor...