A5045270482- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Lipoproteins and Cardiovascular Health
- Atherosclerosis and Cardiovascular Diseases
- Cardiovascular Disease and Adiposity
- Aortic aneurysm repair treatments
- Abdominal vascular conditions and treatments
- Cardiac Valve Diseases and Treatments
- Cardiomyopathy and Myosin Studies
- Dermatological and Skeletal Disorders
- PARP inhibition in cancer therapy
- Metabolism, Diabetes, and Cancer
- Aortic Thrombus and Embolism
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and biosynthesis
- Diet and metabolism studies
- Gallbladder and Bile Duct Disorders
- Mitochondrial Function and Pathology
- Extracellular vesicles in disease
- Immune cells in cancer
- Lipid metabolism and disorders
- Cellular transport and secretion
- Cerebrovascular and Carotid Artery Diseases
- Liver Disease Diagnosis and Treatment
- RNA and protein synthesis mechanisms
Harvard University
2015-2024
Brigham and Women's Hospital
2013-2023
Abstract Aims Calcific aortic valve disease (CAVD) is the most common disease, which consists of a chronic interplay inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as novel key player in pathophysiology CAVD, its role transformation valvular interstitial cells (VICs) into pathological phenotypes explored. Methods results An (AV) wire injury (AVWI) mouse model with deficiency used to determine effects on AV stenosis, vitro experiments employed human...
Vein graft failure remains a common clinical challenge. We applied systems approach in mouse experiments to discover therapeutic targets for vein failure.Global proteomics and high-dimensional clustering on multiple tissues were used identify potential pathogenic mechanisms. The PPARs (peroxisome proliferator-activated receptors) pathway served as an example substantiate our discovery platform. In vivo with macrophage-targeted PPARα small interfering RNA, or the novel, selective activator...
Objectives Angiopoietin-like protein 2 (ANGPTL2), a recently identified pro-inflammatory cytokine, is mainly secreted from the adipose tissue. This study aimed to explore role of ANGPTL2 in tissue inflammation and macrophage activation mouse model diabetes. Methodology/Principal Findings Adenovirus mediated lacZ (Ad-LacZ) or human (Ad-ANGPTL2) was delivered via tail vein diabetic db/db mice. Ad-ANGPTL2 treatment for weeks impaired both glucose tolerance insulin sensitivity as compared...
Proteostasis maintains protein homeostasis and participates in regulating critical cardiometabolic disease risk factors including proprotein convertase subtilisin/kexin type 9 (PCSK9). Endoplasmic reticulum (ER) remodeling through release incorporation of trafficking vesicles mediates secretion degradation. We hypothesized that ER drives mitochondrial fission proteostasis.
Abstract The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional uptake, storage, metabolism contribute to several major human diseases including atherosclerosis obesity. associates with cardiovascular disease; however, role adipose tissue remains unclear. Here we show that low-density lipoprotein receptor-deficient (Ldlr −/− ) model, deficiency (Sort1 female mice suppresses Niemann-Pick type C1-Like 1 (Npc1l1) mRNA levels, reduces body white...
Mass-spectrometry-enabled ADP-ribosylation workflows are developing rapidly, providing researchers a variety of ADP-ribosylome enrichment strategies and mass spectrometric acquisition options. Despite the growth spurt in upstream technologies, systematic ADP-ribosyl (ADPr) peptide spectral annotation methods lacking. HCD-dependent studies common, but resulting MS2 spectra complex, owing to mixture b/y-ions m/p-ion peaks representing one or more dissociation events ADPr moiety (m-ion)...
Roux-en-Y gastric bypass (RYGB) surgery reduces weight in obese patients. A marked decrease blood glucose levels occurs before loss; however, key molecules that improve the glycemic profile remain largely unknown. Using a murine RYGB model, we performed multiorgan proteomics and bioinformatics to monitor proteins molecular pathways change this early response. Multiplexed proteomic kinetics data analysis revealed Roux limb, biliopancreatic liver, pancreas each exhibited unique temporal...
Background: Inflammation and lipid accumulation are major features of atherosclerosis, a leading cause death morbidity worldwide. Our previous study recognized ADP-ribosylation, post-translational modification, as novel regulator macrophage activation. We also have established mass spectrometry-based ADP-ribosylation proteomics. Using this technology, we evaluated the completely uncharacterized role in atherogenesis. hypothesized that ADP-ribosylated proteins circulate from liver, accumulate...
Objective: The sorting receptor Sortilin functions in the regulation of glucose and lipid metabolism. Dysfunctional uptake, storage, metabolism contribute to several major human diseases including atherosclerosis obesity. associates with cardiovascular disease; however, role adipose tissue remains unclear. Approach Results: Here we show that low-density lipoprotein receptor-deficient (Ldlr -/- ) model, deficiency ( Sort1 female mice inhibits intestinal Niemann-Pick type C1-Like 1 (Npc1l1)...
Background: Studying atherosclerotic calcification in vivo requires mouse models with genetic deletion of low-density lipoprotein receptor (Ldlr) or apolipoprotein E. A previous study showed a rapid induction atherosclerosis by proprotein convertase subtilisin/kexin type 9 (PCSK9) mice. Here, we hypothesize that this method is useful tool to cardiovascular non-genetically modified C57BL/6 Results: 10 week old mice received single tail vein injection recombinant adeno-associated viral vector...
Background: Clinical evidence links arterial calcification and cardiovascular risk. Fibrous cap microcalcifications can promote atherosclerotic plaque failure, large calcifications stabilize the plaque. Therefore, morphology determine morbidity, but temporal patterns of calcific mineral deposition growth remain unknown. Results: Apolipoprotein E-deficient ( Apoe-/- ) mice on an atherogenic diet develop calcification. Longitudinal studies were performed using two different fluorescent calcium...
Objectives: Vein graft (VG) failure rates after surgical bypass for PAD remain high, which can cause limb loss. Yet, the underlying mechanisms VG lesion development obscure. We took a systems approach to explore key pathways in mouse model. Approach and Results: implanted inferior vena cava into left carotid artery of fat-fed Ldlr-/- mice monitored up 4 weeks post-surgery. Unbiased proteomic profiling followed by hierarchical clustering showed distinct clusters. One protein cluster is...