A5001254074- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Transplantation: Methods and Outcomes
- Hemoglobin structure and function
- Erythrocyte Function and Pathophysiology
- Organ Transplantation Techniques and Outcomes
- Neonatal Respiratory Health Research
- Heme Oxygenase-1 and Carbon Monoxide
- Mechanical Circulatory Support Devices
- Neuroscience of respiration and sleep
- RNA modifications and cancer
- Pancreatic function and diabetes
- Hemoglobinopathies and Related Disorders
- Atherosclerosis and Cardiovascular Diseases
- Xenotransplantation and immune response
- Respiratory Support and Mechanisms
- RNA Interference and Gene Delivery
- Chronic Obstructive Pulmonary Disease (COPD) Research
- COVID-19 Clinical Research Studies
- Nitric Oxide and Endothelin Effects
- Cardiac Arrest and Resuscitation
- Immune Response and Inflammation
- Adipokines, Inflammation, and Metabolic Diseases
- Phagocytosis and Immune Regulation
- Biological Research and Disease Studies
Vanderbilt University
2014-2025
Vanderbilt University Medical Center
2018-2024
Pulmonary and Allergy Associates
2019
Significance Results from this study represent a breakthrough in our understanding of posttranscriptional control cholesterol metabolism and how microRNAs (miRNAs) are at the heart regulatory circuitry homeostasis. Although cells adept maintaining proper levels, it was unknown posttranscriptionally coordinate uptake, efflux, synthesis. MicroRNA-223 (miR-223) transcription expression maintained by cholesterol, and, as feedback network, miR-223 inhibits biosynthesis uptake increases efflux....
MicroRNAs (miRNAs) have emerged as biomarkers of metabolic status, etiological factors in complex disease, and promising drug targets. Recent reports suggest that miRNAs are critical regulators pathways underlying the pathophysiology type 2 diabetes. In this study, we demonstrate by deep sequencing real-time quantitative PCR hepatic levels Foxa2 mRNA miR-29 elevated a mouse model diet-induced insulin resistance. We also show significantly upregulated livers Zucker diabetic fatty (fa/fa) rats...
Increased endothelial permeability is central to the pathogenesis of sepsis and leads organ dysfunction death but endogenous mechanisms that drive increased are not completely understood. We previously reported cell-free hemoglobin (CFH), elevated in 80% patients with sepsis, increases lung microvascular an ex vivo human model cultured cells. In this study, we augmented a murine polymicrobial circulating CFH test hypothesis by inducing apoptosis. Mice were treated intraperitoneal injection...
Access to life-saving lung transplantation remains limited by a shortage of donor organs. We have previously described rehabilitation discarded human lungs quality suitable for using cross-circulation whole blood between xeno-support swine and lungs. However, the immunologic implications transplanting rehabilitated remain unknown. Human declined clinical (N=5) underwent xenogeneic up 12 hours. To model subsequent transplantation, were re-exposed autologous via normothermic ex vivo machine...
Primary graft dysfunction (PGD) is acute lung injury within 72 hours of transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to PGD by increasing microvascular permeability and tested this in patients, ex vivo human lungs, cultured endothelial cells. In a nested case control study 40 patients with severe at 80 matched controls without PGD, elevated preoperative CFH was independently associated increased risk (odds ratio [OR] 2.75, 95%CI, 1.23–6.16, P = 0.014). The...
The diversity of small non-coding RNAs (sRNA) is rapidly expanding and their roles in biological processes, including gene regulation, are emerging. Most interestingly, sRNAs also found outside cells stably present all fluids. As such, extracellular represent a novel class disease biomarkers likely involved cell signaling intercellular communication networks. To assess potential as biomarkers, can be quantified plasma, urine, other Nevertheless, to fully understand the impact endocrine...
Acute respiratory distress syndrome (ARDS) is an inflammatory lung disorder that frequently complicates critical illness and commonly occurs in sepsis. Although numerous clinical environmental risk factors exist, not all patients with develop ARDS, raising the possibility of genetic underpinnings for ARDS susceptibility. We have previously reported circulating cell-free hemoglobin (CFH) elevated during sepsis, higher levels predict worse outcomes. Excess CFH rapidly scavenged by haptoglobin...
Acute kidney injury is a common complication of severe sepsis and contributes to high mortality. The molecular mechanisms acute during are not fully understood. Because hemoproteins, including myoglobin hemoglobin, known mediate rhabdomyolysis, we hypothesized that cell-free hemoglobin (CFH) would exacerbate sepsis. Sepsis was induced in mice by intraperitoneal injection cecal slurry (CS). To mimic elevated levels CFH observed human sepsis, also received retroorbital or dextrose control....
Improved approaches to expanding the pool of donor lungs suitable for transplantation are critically needed growing population with end-stage lung disease. Cross-circulation (XC) whole blood between swine and explanted human has previously been reported enable extracorporeal recovery that declined due acute, reversible injuries. However, immunologic interactions this xenogeneic platform have not characterized, thus limiting potential translational applications. Using flow cytometry...
The alveolar epithelium is protected by a heparan sulfate-rich, glycosaminoglycan layer called the epithelial glycocalyx. It cleaved in patients with acute respiratory distress syndrome (ARDS) and murine models of influenza A (IAV) infection, shedding fragments into airspace from cell surface. Glycocalyx results increased permeability alveolar-capillary barrier, amplifying lung injury. mechanisms underlying glycocalyx IAV infection are unknown. We hypothesized that induction host sheddases...
Cell-free hemoglobin (CFH) is elevated in the airspace of patients with acute respiratory distress syndrome (ARDS) and sufficient to cause lung injury a murine model. However, pathways through which CFH causes are not well understood. Toll-like receptor 4 (TLR4) mediator inflammation after detection damage- pathogen-associated molecular patterns. We hypothesized that TLR4 signaling mediates proinflammatory effects airspace. After intratracheal CFH, BALBc mice deficient had reduced...
The diversity of small non-coding RNAs (sRNA) is rapidly expanding and their roles in biological processes, including gene regulation, are emerging. Most interestingly, sRNAs also found outside cells stably present all fluids. As such, extracellular represent a novel class disease biomarkers likely involved cell signaling intercellular communication networks. To assess potential as biomarkers, can be quantified plasma, urine, other Nevertheless, to fully understand the impact endocrine...
Cell-free hemoglobin (CFH) is associated with severe lung injury in human patients and sufficient to induce airspace inflammation alveolar–capillary barrier dysfunction an experimental model of acute injury. The mechanisms through which this occurs are unknown. One key pathway regulates during the NLRP3 inflammasome. Because CFH can act as a damage-associated molecular pattern, we hypothesized that may activate inflammasome Primary mouse alveolar macrophages cultured murine exposed (0–1...
Chronic kidney disease (CKD) is associated with endothelial dysfunction and atherosclerosis. High-density lipoproteins (HDL) serve as a general cargo carrier for wide-variety of proteins, nucleic acids, small molecules which likely confer many HDL’s alternative functions. Human coronary artery cells (HCAEC) treated native HDL were found to have increased intracellular levels miR-92a, miRNA recently protect against Moreover, delivery miR-92a was inhibited using SR-BI blocking antibodies in...
Atherosclerosis is associated with endothelial dysfunction and inflammation, high-density lipoproteins (HDL) play critical roles in both. HDL transport a wide-variety of proteins, nucleic acids, small molecules, which likely confer many HDL’s alternative functions, including its anti-inflammatory anti-atherogenic properties. Using vitro studies, we demonstrated that macrophages export miR-223 to subsequently, delivers functional human coronary artery cells (HCAEC). Moreover, intracellular...
In addition to cholesterol, HDL transports a wide-variety of cargo including vitamins, nucleic acids, and diverse set proteins. Outside the reverse cholesterol transport pathway, has alternative functions that contribute its anti-atherogenicity, anti-inflammatory, anti-oxidant, signaling capacities. Recently, we found delivers functional microRNAs recipient cells, which likely confers HDL’s ability suppress adhesion molecule expression in endothelial cells. As such, changes impact many these...
Extracellular small non-coding RNAs (sRNAs) are a new class of disease biomarkers and transferred between cells by high-density lipoproteins (HDL) in novel form intercellular communication. In chronic inflammatory states auto-immunity, HDL can become dysfunctional, likely through alterations its diverse cargo, including changes to sRNA signatures. We have previously found that HDL-microRNAs (miRNA) altered systemic lupus erythematosus (SLE); however, miRNAs just one type sRNAs. As such we...