A5012648118- Platelet Disorders and Treatments
- Antiplatelet Therapy and Cardiovascular Diseases
- Cell Adhesion Molecules Research
- Peripheral Artery Disease Management
- Immune Cell Function and Interaction
- Transplantation: Methods and Outcomes
- Protease and Inhibitor Mechanisms
- Extracellular vesicles in disease
- Genetic and Kidney Cyst Diseases
- Cardiovascular Disease and Adiposity
- Blood Coagulation and Thrombosis Mechanisms
- Cancer-related molecular mechanisms research
- Inflammatory Biomarkers in Disease Prognosis
- HIV-related health complications and treatments
- Autophagy in Disease and Therapy
- Adipokines, Inflammation, and Metabolic Diseases
- Mechanical Circulatory Support Devices
- HIV Research and Treatment
- Cardiac Structural Anomalies and Repair
- Diabetes Treatment and Management
- S100 Proteins and Annexins
- T-cell and B-cell Immunology
- Advanced Glycation End Products research
- Proteoglycans and glycosaminoglycans research
- Renal and related cancers
University of Utah
2019-2023
New York University
2012-2018
University Medical Center
2017
Inserm
2012
Hôpital Necker-Enfants Malades
2012
Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated diabetes. Whether hyperglycemia promotes platelet production whether enhanced contributes to atherothrombosis remains unknown. Here we found response hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting increased of IL-6, pleiotropic...
Background: Mechanisms for increased cardiovascular risk in HIV-1-infected adults are incompletely understood, but platelet activation and immune leading to a prothrombotic state have been proposed as significant contributors. Aspirin has antiplatelet immunomodulatory properties. We explored whether 1 week of low-dose aspirin attenuates virologically suppressed on antiretroviral therapy. Methods: Platelet were measured subjects therapy controls before after aspirin. Results: Compared with...
Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They uniquely positioned decipher genetic signal from environmental noise, with potential application variant expression studies. However, longitudinal analyses in healthy individuals-especially regards alternative splicing-are lacking for most primary cell types, including platelets.To assess splicing platelets use identify novel platelet quantitative trait loci...
Platelets and megakaryocytes are critical players in immune responses. Recent reports suggest infection inflammation alter the megakaryocyte platelet transcriptome to induce altered reactivity. We determined whether nonviral sepsis induces differential gene expression Nonviral upregulated IFN-induced transmembrane protein 3 (IFITM3), an IFN-responsive that restricts viral replication. As IFITM3 has been linked clathrin-mediated endocytosis, we promoted endocytosis of α-granule proteins. IFN...
Protease activated receptor (PAR) 4 (gene: F2RL3) harbors a functional dimorphism, rs773902 A/G (encoding Thr120/Ala120, respectively) and is associated with greater platelet aggregation. The A allele frequency more common in Black individuals, individuals have higher incidence of ischemic stroke than White individuals. However, it not recognized whether the responsible for worse outcomes. To directly test vivo effect this variant on stroke, we generated mice where F2rl3 was replaced by...
Both in humans and animal models, an acute increase plasma insulin levels, typically following meals, leads to transient depression of hepatic secretion very low density lipoproteins (VLDL). One contributing mechanism for the decrease VLDL is enhanced degradation apolipoprotein B100 (apoB100), which required formation. Unlike nascent apoB100, occurs endoplasmic reticulum (ER), insulin-stimulated apoB100 post-ER inhibited by pan-phosphatidylinositol (PI)3-kinase inhibitors. It unclear,...
Abstract Human anucleate platelets cannot be directly modified using traditional genetic approaches. Instead, studies of platelet gene function depend on alternative models. Megakaryocytes (the nucleated precursor to platelets) are the nearest cell in origin, structure, and function. However, achieving consistent modifications primary megakaryocytes has been challenging, functional effects induced deletions human for even well-characterized genes (eg, ITGA2B) unknown. Here we present a rapid...
The small noncoding RNAs (sncRNAs) in megakaryocytes (MKs) and platelets are not well characterized. Neither is the impact of SARS-CoV-2 infection on sncRNAs platelets.To investigate sorting MK into platelets, differences platelet sncRNAomes healthy donors (HDs) COVID-19 patients.We comprehensively profiled from MKs cultured cord blood-derived CD34+ cells, HDs, patients with moderate severe infection. We also Argonaute (AGO)-bound MKs.We characterized can account for ∼95% all sequenced...
Low to moderate inorganic arsenic (iAs) exposure is independently associated with cardiovascular disease (CVD), particularly for patients diabetes mellitus (DM). The mechanism of increased CVD risk from iAs in DM has not been adequately characterized. We evaluated whether increasing concentrations glucose enhance the effects on platelet and megakaryocyte activity, key steps atherothrombosis. Healthy donor whole blood was prepared a standard fashion incubated sodium arsenite range 0 10 µM....
Patients with heart failure (HF) and left ventricular assist devices (LVAD) have dysregulated thrombo-inflammatory responses, mediated in part by platelets. While studies of platelet activation been undertaken HF, changes the transcriptome HF patients following mechanical unloading an LVAD not investigated. We prospectively enrolled longitudinally followed advanced (n = 32) for a mean 57 months post-LVAD implantation. For comparison, healthy donors were also 20). Platelets hyperactive as...
Background: While platelets play a key role in the pathogenesis of atherothrombosis, measuring platelet activity remains research tool. We sought to 1) develop an integrated score (PS) combining multiple measurements, 2) assess its reproducibility over time, 3) investigate correlation pre- and post-aspirin, 4) compare subjects with cardiovascular disease (CVD) versus healthy controls. Methods: Following overnight fast, 48 controls had 4 weekly phlebotomies received 81 mg aspirin daily...
Niacin therapy, used either alone or in combination with another agent to reduced the risk of coronary heart disease, is effective raising and lowering, respectively, HDL‐c apoB/VLDL triglyceride (TG) levels dyslipidemia. To further understand if part mechanism by reducing secretion apoB‐containing lipoproteins through autophagy, we did a series niacin studies isolated primary hepatocytes intact mice. Metabolic labeling pulse‐chase results showed increased intracellular apoB degradation 30%,...
Nephronophthisis, a hereditary nephropathy characterized by interstitial fibrosis and cyst formation, is caused mutations in NPHP genes encoding the ciliary proteins called nephrocystins. We investigate function of nephrocystin-1, -4 -8, vitro vivo mammalian kidney cells zebrafish respectively. Depletion either NPHP1 (N1-KD), NPHP4 (N4-KD) or NPHP8 (N8-KD) shRNA-mediated knockdown MDCK led to abnormal ciliogenesis epithelial morphogenesis defects 3D culture. Moreover nephrocystin-4 modulates...
Nephronophtisis (NPH) is a kidney ciliopathy often associated with extra-renal defects and for which 12 genes (NPHP1-12) have been identified. NPHP1 NPHP4 control the ciliary access at transition zone velocity of some intraflagellar transport (IFT)/BBS proteins in C.elegans. Recently, collaborative effort, we identified, families isolated NPH, mutations TTC21B as well WDR19, encode retrograde IFT-A IFT139 IFT144, respectively. By ciliome sequencing 1600 candidate from 14 NPH patients...