A5025903669- Organ Transplantation Techniques and Outcomes
- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- Liver Disease and Transplantation
- RNA modifications and cancer
- Radiopharmaceutical Chemistry and Applications
- Renal Transplantation Outcomes and Treatments
- Heme Oxygenase-1 and Carbon Monoxide
- Inflammasome and immune disorders
- Macrophage Migration Inhibitory Factor
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Liver Disease Diagnosis and Treatment
- Immune Cell Function and Interaction
- Cancer-related gene regulation
- Pediatric health and respiratory diseases
- Genomics, phytochemicals, and oxidative stress
- MicroRNA in disease regulation
- IL-33, ST2, and ILC Pathways
- Clostridium difficile and Clostridium perfringens research
- Neonatal Health and Biochemistry
- Transplantation: Methods and Outcomes
- Gut microbiota and health
- Monoclonal and Polyclonal Antibodies Research
- Liver physiology and pathology
- Advanced Neuroimaging Techniques and Applications
University of California, Los Angeles
2019-2024
Beckman Research Institute
2008-2022
City of Hope
2008-2022
City Of Hope National Medical Center
2008-2022
Novem (Netherlands)
2020
California State University, Fullerton
1997
West Los Angeles College
1996
Although modifications of gut microbiota with antibiotics (Abx) influence mouse skin and cardiac allografts, its role in orthotopic liver transplantation (OLT) remains unknown. We aimed to determine whether how recipient Abx pretreatment may affect hepatic ischemia-reperfusion injury (IRI) OLT outcomes. Mice (C57BL/6) or without treatment (10 days) were transplanted allogeneic (BALB/c) cold-stored (18 hours) livers, followed by blood sampling (6 hours). divided 264 human recipients on the...
Although Ikaros (IKZF1) is a well-established transcriptional regulator in leukocyte lymphopoiesis and differentiation, its role myeloid innate immune responses remains unclear. Sirtuin 1 (SIRT1) histone/protein deacetylase involved cellular senescence, inflammation, stress resistance. Whether SIRT1 signaling essential cell activation uncertain, while the molecular communication between SIRT1, two major regulators, has not been studied.We undertook functional studies to interrogate...
Neutrophils, the largest innate immune cell population in humans, are primary proinflammatory sentinel ischemia-reperfusion injury (IRI) mechanism orthotopic liver transplantation (OLT). Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1, CC1, or CD66a) is essential neutrophil activation and serves as a checkpoint regulator of immune-driven IRI cascade OLT. Although CC1 alternative splicing generates two functionally distinct short long cytoplasmic isoforms, their role remains...
Although cold preservation remains the gold standard in organ transplantation, stress–induced cellular injury is a significant problem clinical orthotopic liver transplantation (OLT). Because recent study showed that stress activates ferroptosis, form of regulated cell death, we investigated whether and how ferroptosis determines OLT outcomes mice humans. Treatment with inhibitor (ferrostatin-1) during reduced lipid peroxidation (malondialdehyde; MDA), primarily sinusoidal endothelial cells...
Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic transplantation (OLT) remains elusive. We aimed to determine whether/how signaling may affect hepatic ischemia-reperfusion (IRI) OLT outcomes. In mouse, donor CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression HMGB1 translocation during cold storage, data supported vitro studies where flush from CC1-deficient livers enhanced macrophage...
Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We shown that carcinoembryonic antigen–related cell adhesion molecule (Ceacam1; CD66a ), a transmembrane biliary glycoprotein expressed epithelial, endothelial, immune cells, determines donor liver transplant quality. Here, we studied how AS of Ceacam1 affects ischemia-reperfusion injury (IRI) mouse human...
Imbalances in the redox state of liver arise during metabolic processes, inflammatory injuries, and proliferative disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels oxidative stress (OxS) that occur response hepatic ischemia/reperfusion injury (IRI) diseases liver. Antisense oligonucleotides (ASOs) are an emerging class gene expression modulators target RNA molecules by Watson–Crick binding specificity, leading degradation, splicing modulation,...
Fibromyalgia syndrome (FMS) is a chronic musculoskeletal pain disorder affecting 2% to 5% of the general population. Both genetic and environmental factors may be involved. To ascertain in an unbiased manner which genes play role disorder, we performed complete exome sequencing on subset FMS patients. Out 150 nuclear families (trios) DNA from 19 probands was subjected sequencing. Since >80,000 SNPs were found per proband, data further filtered, including analysis those with stop codons, rare...
Despite tremendous progress in understanding the mechanisms of constitutive and alternative splicing, an important widespread step along gene expression pathway, our ability to deliberately regulate at this remains rudimentary. The present study was performed investigate whether a theophylline-dependent "splice switch" that sequesters branchpoint sequence (BPS) within RNA-theophylline complex can splicing.We constructed series pre-mRNAs which BPS inserted theophylline aptamer. We show...
Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) acts through homophilic and heterophilic interactions with T immunoglobulin domain mucin domain-containing protein 3 (TIM-3), which regulates innate immune activation in orthotopic liver transplantation (OLT). We investigated whether cluster of differentiation (CD) 4
Abstract Sirtuin 1 (SIRT1) is a histone/protein deacetylase in the cellular response to inflammatory, metabolic, and oxidative stressors. We previously reported that myeloid SIRT1 regulates inflamed liver’s canonical pyroptosis cell death pathway. However, whether/how hepatocyte engaged programmed cold-stressed liver remains uncertain. Here, we undertook translational studies human mouse orthotopic transplantation (OLT) interrogate significance of hepatocyte-specific cold-stored donor livers...
Interferon regulatory factor-1 (IRF-1) is a master regulator of IFN-γ induced gene transcription. Previously we have shown that IRF-1 transcriptionally induces CEACAM1 via an ISRE (Interferon-Stimulated Response Element) in its promoter. pre-mRNA undergoes extensive alternative splicing (AS) generating isoforms to produce either short (S) cytoplasmic domain expressed primarily epithelial cells or as ITIM-containing long (L) isoform immune cells. The transcriptional and molecular mechanism...
Abstract Th17 cells are a class of Th that secrete IL-17 and mediate pathogenic immunity responsible for autoimmunity including experimental autoimmune encephalomyelitis, murine model multiple sclerosis. Retinoic acid–related orphan receptor γ t (RORγt) is the critical transcription factor controls differentiation cells. However, little known about transcriptional cofactors RORγt in regulation differentiation. In this study, we demonstrate protein arginine N-methyltransferase 1 (PRMT1)...
Ischemia-reperfusion injury (IRI) represents a risk factor in liver transplantation (LT). We have shown that overexpression of heme oxygenase-1 (HO-1) mitigates hepatic IRI LT recipients. Here, we hypothesized human antigen R (HuR), the stabilizer adenylate-uridylate (AU)-rich mRNAs, is required for hepatoprotection LT.In an experimental arm, HuR/HO-1 protein expression was correlated with phenotype. In vitro inflammation mimic model warm IRI, induction and cytoplasmic localization following...