A5082923692- Immune Cell Function and Interaction
- Alcohol Consumption and Health Effects
- CAR-T cell therapy research
- Virus-based gene therapy research
- Gut microbiota and health
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Tryptophan and brain disorders
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Cancer Research and Treatments
- IL-33, ST2, and ILC Pathways
- Cancer-related gene regulation
- Immune cells in cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Liver Disease Diagnosis and Treatment
- Cancer-related molecular mechanisms research
- Diet and metabolism studies
- COVID-19 Clinical Research Studies
- Stress Responses and Cortisol
- Viral gastroenteritis research and epidemiology
- Colorectal Cancer Screening and Detection
- Clostridium difficile and Clostridium perfringens research
- Lung Cancer Treatments and Mutations
- Cancer Mechanisms and Therapy
City Of Hope National Medical Center
2021-2025
University of California, Irvine
2019-2022
City of Hope
2021
University of California, Riverside
2014-2019
University of Manchester
1996
A comprehensive analysis and characterization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection model that mimics non-severe disease 2019 (COVID-19) in humans is warranted for understating the virus developing preventive therapeutic agents. Here, we characterized K18-hACE2 mouse expressing human (h)ACE2 mice, controlled by keratin 18 (K18) promoter, epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found intranasal...
Abstract IL15 is a pleiotropic cytokine with multiple roles that improve immune responses to tumor cells. Oncolytic viruses (OV) specifically lyse tumors and activate responses. Systemic administration of or its complex the IL15Rα chimeric antigen receptor (CAR) natural killer (NK) cells are currently being tested in clinic. Here, we generated herpes simplex 1–based OV-expressing human IL15/IL15Rα sushi domain fusion protein (named OV-IL15C), as well off-the-shelf EGFR-CAR NK cells, studied...
N 6-methyladenosine (m6A) is the most prevalent posttranscriptional modification on RNA. NK cells are predominant innate lymphoid that mediate antiviral and antitumor immunity. However, whether how m6A modifications affect cell immunity remain unknown. Here, we discover YTHDF2, a well-known reader, upregulated in upon activation by cytokines, tumors, cytomegalovirus infection. Ythdf2 deficiency impairs activity vivo. YTHDF2 maintains homeostasis terminal maturation, correlating with...
Abstract Lung cancer remains the most common cause of death. Given continued research into new drugs and combination therapies, outcomes in lung have been improved, clinical benefits expanded to a broader patient population. However, overall cure survival rates for patients remain low, especially metastatic cases. Among available treatment options, such as surgery, radiation therapy, chemotherapy, targeted alternative immunotherapy has shown be promising. The exponential progress...
Pre-pregnancy (pregravid) obesity has been linked to several adverse health outcomes for both mother and offspring. Complications during pregnancy include increased risk gestational diabetes, hypertension, preeclampsia, placental abruption, difficulties delivery. Several studies suggest that these negative are mediated by heightened systemic inflammation as well changes in development function. However, the molecular mechanisms which pregravid affects processes poorly understood. In this...
Diarrhea is the second leading cause of death in children under 5 years age. Enhanced understanding causal pathways, pathogenesis, and sequelae diarrhea urgently needed. Although gut microbiota believed to play a role susceptibility diarrheal diseases, our this association remains incomplete. Infant rhesus macaques (Macaca mulatta) are susceptible making them an ideal model address question. The maturation infant macaque microbiome throughout first 8 months life occurs similar pattern as...
Spliced X-box-binding protein 1 (XBP1s) is an essential transcription factor downstream of interleukin-15 (IL-15) and AKT signaling, which controls cell survival effector functions human natural killer (NK) cells. However, the precise mechanisms, especially targets XBP1s, remain unknown. In this study, by using XBP1 conditional knockout mice, we found that XBP1s critical for IL-15-mediated NK but not proliferation in vitro vivo. Mechanistically, regulates homeostatic targeting PIM-2, a...
Alcohol use disorder (AUD) results in increased intestinal permeability, nutrient malabsorption, and risk of colorectal cancer (CRC). Our understanding the mechanisms underlying these morbidities remains limited because studies to date have relied almost exclusively on short-term heavy/binge drinking rodent models colonic biopsies/fecal samples collected from AUD subjects with alcoholic liver disease (ALD). Consequently, dose- site-dependent impact chronic alcohol consumption absence overt...
NKp46 is a critical regulator of natural killer (NK) cell immunity, but its function in non-NK innate immune cells remains unclear. Here, we show that indispensable for expressing IL-2 receptor-α (IL-2Rα) by liver-resident type-1 lymphoid (ILC1s). Deletion reduces IL-2Rα on ILC1s downregulating NF-κB signaling, thus impairing ILC1 proliferation and cytotoxicity vitro vivo. The binding anti-NKp46 antibody to triggers the activation NF-κB, expression IL-2Rα, interferon-γ (IFN-γ), tumor...
Abstract Several lines of evidence indicate that chronic alcohol use disorder leads to increased susceptibility several viral and bacterial infections, whereas moderate consumption decreases the incidence colds improves immune responses some pathogens. In line with these observations, we recently showed heavy ethanol intake (average blood concentrations > 80 mg/dl) suppressed, (blood < 50 enhanced, T B cell modified vaccinia Ankara vaccination in a nonhuman primate model...
Abstract Trogocytosis is a fast, cell–cell contact-dependent uptake of membrane patches and associated molecules by one cell from another. Here, we report our investigation trogocytosis TYRO3, protein, tumor target cells to natural killer (NK) the functional consequences for NK cells. We found that although did not express endogenous TYRO3 on surface, activated rapidly acquired via in vitro vivo. which termed TYRO3+ cells, had significantly enhanced cytotoxicity IFNγ production as well...
The E3 ubiquitin ligase Cbl-b has been characterized as an intracellular checkpoint in T cells; however, the function of primary human NK cells, innate immune anti-tumor effector cell, is not well defined. In this study, we show that expression significantly upregulated cells activated by IL-15, IL-2, and cell-sensitive tumor cell line K562 lacks MHC class I expression. Pretreatment with JAK or AKT inhibitors prior to IL-15 stimulation reversed upregulation. Downregulation resulted...
Abstract Environmental enteric dysfunction is associated with malnutrition as well infant growth stunting and has been classically defined by villous blunting, decreased crypt-to-villus ratio, inflammation in the small intestine. Here, we characterized environmental among rhesus macaques that are naturally exposed to pathogens commonly linked human stunting. Remarkably, despite atrophy histological abnormalities observed intestine, poor trajectories low serum tryptophan levels were...
Abstract A comprehensive analysis and characterization of a SARS-CoV-2 infection model that mimics non-severe severe COVID-19 in humans is warranted for understating the virus developing preventive therapeutic agents. Here, we characterized K18-hACE2 mouse expressing human (h)ACE2 mice, controlled by keratin 18 (K18) promoter, epithelia, including airway epithelial cells where infections typically start. We found intranasal inoculation with higher viral doses (2×10 3 2×10 4 PFU) caused...
microRNAs (miRNAs) are small noncoding RNAs that key regulators of biological processes, including the immune response to viral infections. Differential expression levels cellular miRNAs and their predicted targets have been described in lungs H1N1-infected BALB/c mice, H5N1 influenza-infected cynomolgus macaques, peripheral blood mononuclear cells (PBMCs) critically ill patients infected with 2009 pandemic H1N1. However, a longitudinal analysis changes during influenza infection how they...
Limited therapeutic options are available for patients with breast cancer brain metastases (BCBM), and thus there is an urgent need novel treatment approaches. We previously engineered effective oncolytic herpes simplex virus 1 (oHSV) expressing a full-length anti-CD47 monoclonal antibody (mAb) human IgG1 scaffold (OV-αCD47-G1) that was used to treat both ovarian glioblastoma. Here, we demonstrate the combination of OV-αCD47-G1 temozolomide (TMZ) improve outcomes in preclinical models BCBM....
Chronic heavy alcohol consumption, also referred to as chronic drinking (CHD), results in intestinal injury characterized by increased permeability, dysbiosis, nutrient malabsorption, potentially higher susceptibility infection, and risk of colorectal cancer. However, our understanding the mechanisms which CHD damage remains incomplete. Here, we investigated impact on transcriptional functional responses lamina propria leukocytes (LPLs) isolated from 4 major gut sections. Although no...
Abstract Recently developed therapeutics for multiple myeloma (MM) include targeted therapy, immunomodulatory drugs, and immunotherapy, the latter of which consists B-cell maturation antigen (BCMA)-CAR cells, bispecific antibodies (BsAbs) to engage T cells. However, challenges including relapse toxicity still exist. The orphan G protein-coupled receptor, class C group 5 member D (GPRC5D), emerged as a novel target MM therapy. Therefore, following our established system [Cancer Immunol Res...
<div>Abstract<p>IL15 is a pleiotropic cytokine with multiple roles that improve immune responses to tumor cells. Oncolytic viruses (OV) specifically lyse tumors and activate responses. Systemic administration of IL15 or its complex the IL15Rα chimeric antigen receptor (CAR) natural killer (NK) cells are currently being tested in clinic. Here, we generated herpes simplex 1–based OV-expressing human IL15/IL15Rα sushi domain fusion protein (named OV-IL15C), as well off-the-shelf...