A5028966182- Adenosine and Purinergic Signaling
- Neuroscience of respiration and sleep
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Adipokines, Inflammation, and Metabolic Diseases
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal Respiratory Health Research
- Cardiovascular Disease and Adiposity
- Sleep and related disorders
- Nanoplatforms for cancer theranostics
- MicroRNA in disease regulation
- Mechanical Circulatory Support Devices
- Peptidase Inhibition and Analysis
- Cytomegalovirus and herpesvirus research
- Vagus Nerve Stimulation Research
- Cardiac Arrest and Resuscitation
- Intensive Care Unit Cognitive Disorders
- Heme Oxygenase-1 and Carbon Monoxide
- RNA Interference and Gene Delivery
- Bladder and Urothelial Cancer Treatments
- Adrenal Hormones and Disorders
- Immunodeficiency and Autoimmune Disorders
- COVID-19 Impact on Reproduction
- Adolescent and Pediatric Healthcare
Beth Israel Deaconess Medical Center
2016-2025
Harvard University
2016-2025
UC San Diego Health System
2023-2025
University of California, San Diego
2023-2025
Hadassah Medical Center
2020
Sichuan University
2016
State Key Laboratory of Biotherapy
2016
Ashwini Hospital
2014
LMU Klinikum
2011-2013
Ludwig-Maximilians-Universität München
2008-2013
Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying potentially reversing cell exhaustion. Herein, we show the ectonucleotidse CD39 a marker exhausted CD8+ cells. specific HCV or HIV high levels CD39, but those EBV CMV do not. expressed by in infection enzymatically active, co-expressed with PD-1, marks transcriptional signature correlates...
T cells must migrate in order to encounter antigen-presenting (APCs) and execute their varied functions immune defense inflammation. ATP release autocrine signaling through purinergic receptors contribute cell activation at the synapse that form with APCs. Here, we show also require for migration We found chemokine stromal-derived factor-1α (SDF-1α) triggered mitochondrial production, rapid bursts of release, increased primary human CD4+ cells. This process depended on pannexin-1 channels...
Polymorphonuclear neutrophils (PMNs) form the first line of defense against invading microorganisms. We have shown previously that ATP release and autocrine purinergic signaling via P2Y2 receptors are essential for PMN activation. Here we show mitochondria provide initiates Stimulation formyl peptide increases mitochondrial membrane potential (Δψm) triggers a rapid burst from PMNs. This can be blocked by inhibitors production requires an initial receptor-induced Ca2+ signal The generated...
Acquired glucocorticoid resistance frequently complicates the therapy of sepsis. It leads to an exaggerated proinflammatory response and has been related altered expression profiles receptor isoforms receptor-α (mediating anti-inflammatory effects) receptor-β (acting as a dominant negative inhibitor). We investigated impact on effects in human T-cells. hypothesized that 1) changes ratio 2) is controlled by microRNA-mediated gene silencing.Laboratory-based study.University research...
Neutrophils use chemotaxis to locate invading bacteria. Adenosine triphosphate (ATP) release and autocrine purinergic signaling via P2Y2 receptors at the front A2a back of cells regulate chemotaxis. Here, we examined intracellular mechanisms that control these opposing mechanisms. We found mitochondria deliver ATP stimulates in response chemotactic cues, promote mTOR signaling, which augments mitochondrial activity near cells. Blocking with rapamycin or PP242 production (e.g., CCCP) reduced...
We analyzed prospectively whether MGMT (O(6)-methylguanine-DNA methyltransferase) mRNA expression gains prognostic/predictive impact independent of promoter methylation in malignant glioma patients undergoing radiotherapy with concomitant and adjuvant temozolomide or alone. As DNA-methyltransferases (DNMTs) are the enzymes responsible for setting up maintaining DNA patterns eukaryotic cells, we further, is associated upregulation DNMT expression.ADULT PATIENTS WITH A HISTOLOGICALLY PROVEN...
Aeroallergens and ATP elicit cysteinyl leukotrienes from nasal brush cells through the purinergic receptor P2Y2.
The choice of reliable reference genes is a prerequisite for valid results when analyzing gene expression with real-time quantitative PCR (qPCR). This method frequently applied to study patterns in immune cells, yet thorough validation potential still lacking most leukocyte subtypes and models their vitro stimulation. In the current study, we evaluated stability common two widely used cell culture models-anti-CD3/CD28 activated T cells lipopolysaccharide stimulated neutrophils-as well as...
Pediatric intensive care patients are particularly susceptible to severe bacterial infections because of ineffective neutrophil responses. The reasons why neutrophils newborns less responsive than those adults not clear. Because adenosine triphosphate (ATP) and (ADO) tightly regulate neutrophils, we studied whether the ATP ADO levels in blood newborn mice could impair function their neutrophils. We observed significant changes plasma throughout lifespan mice. were significantly higher older...
The phosphodiesterase inhibitor pentoxifylline (PTX) exerts multiple beneficial immunomodulatory effects in states of hyperinflammation. However, the exact mechanism action still remains elusive, and clinical PTX cannot be reliably predicted. In immune cells, G protein-coupled adenosine A2A receptor (A2AR) strong anti-inflammatory effects. As amplifies signaling pathways downstream Gs receptors, A2AR-signaling pathway might involved mediation immune-suppressive PTX. Here, we investigated...
T cells must migrate to encounter antigen-presenting and perform their roles in host defense. Here, we found that autocrine stimulation of the purinergic receptor P2Y11 regulates migration human CD4 cells. receptors redistributed from front back polarized where they triggered intracellular cAMP/PKA signals attenuated mitochondrial metabolism at back. The absence resulted hotspots localized ATP production stimulated P2X4 receptors, Ca2+ influx, pseudopod protrusion front. This regulatory...
T cell suppression in sepsis is a well-known phenomenon; however, the underlying mechanisms are not fully understood. Previous studies have shown that stimulation up-regulates mitochondrial adenosine triphosphate (ATP) production to fuel purinergic signaling necessary for adequate responses. Here we show basal ATP production, release, and of P2X1 receptors represent standby mechanism antigen recognition. Inhibition this process impairs vigilance ability cells trigger activation, up-regulate...
Sepsis remains an unresolved clinical problem. Therapeutic strategies focusing on inhibition of neutrophils (polymorphonuclear neutrophils) have failed, which indicates that a more detailed understanding the underlying pathophysiology sepsis is required. Polymorphonuclear neutrophil activation and chemotaxis require cellular adenosine triphosphate release via pannexin-1 channels fuel autocrine feedback purinergic receptors. In current study, we examined roles endogenous systemic...
T cell suppression contributes to immune dysfunction in sepsis. However, the underlying mechanisms are not well-defined. Here, we show that exposure of human peripheral blood mononuclear cells bacterial lipopolysaccharide (LPS) can rapidly and dose-dependently suppress interleukin-2 (IL-2) production proliferation. We also report these effects depend on monocytes. LPS did prevent interaction monocytes with cells, nor it induce programmed death protein 1 (PD-1) signaling causes suppression....
Bladder cancer is amongst the most common causes of death worldwide. Muscle-invasive bladder (MIBC) bears a particularly poor prognosis. Overexpression purinergic P2X receptors (P2XRs) has been associated with worse outcome in several malignant tumors. Here, we investigated role P2XRs cell proliferation vitro and prognostic value P2XR expression MIBC patients. Cell culture experiments T24, RT4, non-transformed TRT-HU-1 cells revealed link between high ATP concentrations supernatants lines...
Sinonasal mucosal melanoma (SNMM) is a rare but aggressive tumor with poor prognosis. The co-inhibitory receptors T cell immunoglobulin and mucinodomain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3) immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) are promising new targets in anti-cancer immunotherapy. expression profiles of these immune checkpoint molecules (ICMs) potential prognostic implications have not been characterized SNMM yet. Immunohistochemical staining...