A5069114748- Immune cells in cancer
- Autophagy in Disease and Therapy
- Advanced Glycation End Products research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Nanoplatforms for cancer theranostics
- Immune Response and Inflammation
- Heme Oxygenase-1 and Carbon Monoxide
- Nitric Oxide and Endothelin Effects
- Eicosanoids and Hypertension Pharmacology
- Inflammasome and immune disorders
- Liver Disease Diagnosis and Treatment
- Epigenetics and DNA Methylation
- Cancer, Stress, Anesthesia, and Immune Response
- Extracellular vesicles in disease
- Sepsis Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Cell death mechanisms and regulation
- Cardiac Ischemia and Reperfusion
- Phagocytosis and Immune Regulation
- Organ Transplantation Techniques and Outcomes
- Immune Cell Function and Interaction
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Peroxisome Proliferator-Activated Receptors
- Adipose Tissue and Metabolism
- Pharmacogenetics and Drug Metabolism
University of Pittsburgh
2016-2025
University of Pittsburgh Medical Center
2013-2023
UPMC Presbyterian
2013-2016
Huazhong University of Science and Technology
2016
Heidelberg University
2016
Glenmark Pharmaceuticals (Switzerland)
2016
May Institute
2016
Light Chain Bioscience (Switzerland)
2016
UPMC Hillman Cancer Center
2009-2014
Shanghai Tenth People's Hospital
2014
Autophagy clears long-lived proteins and dysfunctional organelles generates substrates for adenosine triphosphate production during periods of starvation other types cellular stress. Here we show that high mobility group box 1 (HMGB1), a chromatin-associated nuclear protein extracellular damage-associated molecular pattern molecule, is critical regulator autophagy. Stimuli enhance reactive oxygen species promote cytosolic translocation HMGB1 thereby autophagic flux. directly interacts with...
Abstract Risks of tumor recurrence after surgical resection have been known for decades, but the mechanisms underlying treatment failures remain poorly understood. Neutrophils, first-line responders stress, may play an important role in linking inflammation to cancer progression. In response neutrophils can expel their protein-studded chromatin form local snares as neutrophil extracellular traps (NET). this study, we asked whether, a result its ability ensnare moving cells, NET formation...
Innate immunity plays a crucial role in the response to sterile inflammation such as liver ischemia/reperfusion (I/R) injury. The initiation of I/R injury results release damage‐associated molecular patterns, which trigger an innate immune and inflammatory cascade through pattern recognition receptors. Neutrophils are recruited after contribute organ damage responses. Formation neutrophil extracellular traps (NETs) has been recently found various stimuli. However, NETs during remains...
Nonalcoholic steatohepatitis (NASH) is a progressive, inflammatory form of fatty liver disease. It the most rapidly rising risk factor for development hepatocellular carcinoma (HCC), which can arise in NASH with or without cirrhosis. The signals promoting progression to HCC remain largely unknown. propensity neutrophils expel decondensed chromatin embedded proteins, known as neutrophil extracellular traps (NETs), has been shown be important chronic conditions and cancer progression. In this...
Thrombosis and inflammation are intricately linked in several major clinical disorders, including disseminated intravascular coagulation acute ischemic events. The damage-associated molecular pattern molecule high-mobility group box 1 (HMGB1) is upregulated by activated platelets multiple inflammatory diseases; however, the contribution of platelet-derived HMGB1 thrombosis remains unexplored. Here, we generated transgenic mice with platelet-specific ablation determined that a critical...
Abstract The balance between apoptosis (“programmed cell death”) and autophagy survival”) is important in tumor development response to therapy. Here, we show that high mobility group box 1 (HMGB1) p53 form a complex regulates the death survival. We knockout of HCT116 cells increases expression cytosolic HMGB1 induces autophagy. Conversely, mouse embryonic fibroblasts localization decreases thus negative regulator HMGB1/Beclin complex, promotes setting diminished p53. HMGB1-mediated survival...
Neutrophil infiltration and neutrophil extracellular traps (NET) in solid cancers are associated with poorer prognosis, but the mechanisms incompletely understood. We hypothesized that NETs enhance mitochondrial function tumor cells, providing extra energy for accelerated growth. Metastatic colorectal cancer tissue showed increased intratumoral supranormal preoperative serum MPO-DNA, a NET marker. Higher MPO-DNA correlated shorter survival. In mice, subcutaneous implants hepatic metastases...
Background and Aims Itaconate, a metabolite of the tricarboxylic acid cycle, plays anti‐inflammatory roles in macrophages during endotoxemia. The mechanisms underlying its have been shown to be mediated by modulation oxidative stress, an important mechanism hepatic ischemia–reperfusion (I/R) injury. However, role itaconate liver I/R injury is unknown. Approach Results We found that deletion immune‐responsive gene 1 (IRG1), encoding for enzyme producing itaconate, exacerbated systemic...
Abstract Surgical removal of malignant tumors is a mainstay in controlling most solid cancers. However, surgical insult also increases the risk tumor recurrence and metastasis. Tissue trauma activates innate immune system locally systemically, mounting an inflammatory response. Platelets neutrophils are two crucial players early response that heals tissues, but their actions may contribute to cancer cell dissemination distant Here we report stress–activated platelets enhance formation...
Adaptive responses to sepsis are necessary prevent organ failure and death. Cellular signaling that limit cell death structural damage allow a withstand insult from irreversible dysfunction. One such protective pathway reduce hepatocellular injury is the up-regulation of heme oxygenase-1 (HO-1) signaling. HO-1 up-regulated in liver response multiple stressors, including lipopolysaccharide (LPS), has been shown Another recently recognized rudimentary cellular autophagy. The aim these...
Cellular processes that drive sterile inflammatory injury after hepatic ischemia/reperfusion (I/R) are not completely understood. Activation of the inflammasome plays a key role in response to invading intracellular pathogens, but mounting evidence suggests it also inflammation driven by endogenous danger-associate molecular pattern molecules released ischemic injury. The nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) is one such process, and mechanism which its...
Abstract The morbidity associated with bacterial sepsis is the result of host immune responses to pathogens, which are dependent on pathogen recognition by pattern receptors, such as TLR4. TLR4 expressed a range cell types, yet mechanisms cell-specific functions lead an integrated response poorly understood. To address this, we generated mice in was specifically deleted from myeloid cells (LysMTLR4KO) or hepatocytes (HCTLR4KO) and then determined survival, counts, inflammatory responses,...
Abstract High mobility group box 1 (HMGB1) is a DNA-binding protein that possesses cytokinelike, proinflammatory properties when released extracellularly in the C23–C45 disulfide form. HMGB1 also plays key role as mediator of acute and chronic inflammation models sterile injury. Although interacts with multiple pattern recognition receptors (PRRs), many its effects injury occur through an interaction toll-like receptor 4 (TLR4). directly TLR4/myeloid differentiation 2 (MD2) complex, although...
Abstract Administration of high-dose interleukin-2 (HDIL-2) has durable antitumor effects in 5% to 10% patients with melanoma and renal cell carcinoma. However, treatment is often limited by side effects, including reversible, multiorgan dysfunction characterized a cytokine-induced systemic autophagic syndrome. Here, we hypothesized that the autophagy inhibitor chloroquine would enhance IL-2 immunotherapeutic efficacy limit toxicity. In an advanced murine metastatic liver tumor model,...
Venous thromboembolic (VTE) disease, consisting of deep venous thrombosis (DVT) and pulmonary embolism (PE) is a leading cause morbidity mortality. Current prophylactic measures are insufficient to prevent all occurrence in part due an incomplete understanding the underlying pathophysiology. Mounting evidence describes interplay between activation innate immune system thrombus development. Recent work has demonstrated that platelet release HMGB1 leads increased microvascular complications...
High-mobility group box 1 (HMGB1) is an abundant chromatin-associated nuclear protein and released into the extracellular milieu during liver ischemia-reperfusion (I/R), signaling activation of proinflammatory cascades. Because intracellular function HMGB1 sterile inflammation I/R currently unknown, we sought to determine role in hepatocytes after I/R. When hepatocyte-specific knockout (HMGB1-HC-KO) control mice were subjected a nonlethal warm I/R, it was found that HMGB1-HC-KO had...
High mobility group box-1 (HMGB1), a ubiquitous nuclear protein, acts as late mediator of lethality when released extracellularly during sepsis. The major source circulating HMGB1 in sepsis is hepatocytes. However, the mechanism release hepatocytes not very clear. We have previously shown that bacterial endotoxin (LPS) sensing pathways, including TLR4 and caspase-11 regulate hepatocyte response to LPS. Here, we report novel function GSDMD LPS-induced active from endotoxemia was...
The ability of cancer cells to survive and grow under hypoxic conditions has been known for decades, but the mechanisms remain poorly understood. Under certain conditions, undergo changes in their bioenergetic profile favor mitochondrial respiration by activating peroxisome proliferator–activated receptor gamma coactivator 1 alpha (PGC‐1α) up‐regulating biogenesis. In this study, we hypothesized that augmented biogenesis plays a critical role hypoxia. Consistent with hypothesis, both human...
Liver ischemia-reperfusion (I/R) injury occurs through induction of oxidative stress and release damage-associated molecular patterns (DAMPs), including cytosolic DNA released from dysfunctional mitochondria or the nucleus. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) is a sensor known to trigger stimulator interferon genes (STING) downstream type 1 (IFN-I) pathways, which are pivotal innate immune system responses pathogen. However, little about role...
Background: Neutrophil extracellular traps (NETs) are generated when activated neutrophils, driven by PAD4, release their DNA, histones, HMGB1, and other intracellular granule components. NETs play a role in acute pancreatitis, worsening pancreatic inflammation, promoting duct obstruction. The autophagy inhibitor chloroquine (CQ) inhibits NET formation; therefore, we investigated the impact of CQ mediated inhibition murine models pancreatitis human correlative studies. Methods: L-arginine...