- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Cytokine Signaling Pathways and Interactions
- SARS-CoV-2 and COVID-19 Research
- Cancer Genomics and Diagnostics
- COVID-19 Clinical Research Studies
- Ferroptosis and cancer prognosis
- Inflammatory Bowel Disease
- Extracellular vesicles in disease
- Lung Cancer Treatments and Mutations
- Glioma Diagnosis and Treatment
- DNA Repair Mechanisms
- Single-cell and spatial transcriptomics
- Lung Cancer Research Studies
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Bioactive Compounds and Antitumor Agents
- Monoclonal and Polyclonal Antibodies Research
- Helicobacter pylori-related gastroenterology studies
- Microtubule and mitosis dynamics
- Psoriasis: Treatment and Pathogenesis
- Cancer, Hypoxia, and Metabolism
- Radiomics and Machine Learning in Medical Imaging
- Synthesis and Reactions of Organic Compounds
Rabin Medical Center
2020-2024
Holon Institute of Technology
2024
Tel Aviv University
2011-2018
Sheba Medical Center
2017
Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response messenger RNA vaccines is unclear.
Patients with inflammatory bowel diseases (IBD), specifically those treated anti-tumor necrosis factor (TNF)α biologics, are at high risk for vaccine-preventable infections. Their ability to mount adequate vaccine responses is unclear. The aim of the study was assess serologic messenger RNA-Coronavirus Disease 2019 vaccine, and safety profile, in patients IBD stratified according therapy, compared healthy controls (HCs).Prospective, controlled, multicenter Israeli study. Subjects enrolled...
The DNA damage response (DDR) is a complex signaling network that leads to repair while modulating numerous cellular processes. double-strand breaks (DSBs), highly cytotoxic lesion, activate this system most vigorously. DSB orchestrated by the ATM protein kinase, which phosphorylates key players in its various branches. Proteasome-mediated degradation plays an important role proteome dynamics following induction. Here, we identify nuclear proteasome activator PA28γ (REGγ; PSME3) as novel DDR...
Introduction Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes blood plasma to gain better understanding resistance. Methods Pre-treatment (T0) (T1) samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma was...
PURPOSE Current guidelines for the management of metastatic non–small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination chemotherapy. This approach fails to account individual patient variability and host immune factors often results less-than-ideal outcomes. To address limitations current guidelines, we developed subsequently blindly validated a machine learning algorithm using pretreatment plasma...
Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- NK-cell activity stimulates IFNγ production. The of naturally blocked by high-affinity endogenous binding protein (IL18BP). IL18BP induced in the tumor microenvironment (TME) response upregulation negative feedback mechanism. In this study, we found that upregulated TME compared with...
The success of the human body in fighting SARS-CoV2 infection relies on lymphocytes and their antigen receptors. Identifying characterizing clinically relevant receptors is utmost importance.
Abstract Background Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of receptor tyrosine kinases characterized in humans. These proteins involved tissue organization, synaptic plasticity, vascular development and progression various diseases including cancer. The kinase member EphB6 is a pseudokinase which has not attracted an equivalent amount interest as its enzymatically-active counterparts. aim this study was to assess expression pituitary tumors....
Glioblastoma (GBM) is the most common type of glioma and uniformly fatal. Currently, tumour heterogeneity mutation acquisition are major impedances for tailoring personalized therapy. We collected blood tissue samples from 25 GBM patients healthy controls. Cell-free DNA (cfDNA) was extracted plasma Tumour fresh samples. Extracted sequenced using a whole-genome sequencing procedure. also 180 datasets publicly available at TCGA/PANCANCER project. These data were analysed mutations gene-gene...
Abstract Background and Aims Janus kinase [JAK] inhibitors are used for treating inflammatory bowel diseases [IBD]. We aimed to identify the molecular effects of JAK inhibition in human intestinal mucosa, considering IBD location phenotype. Methods Colonic ileal explants from patients with ulcerative colitis [UC], Crohn’s disease [CD], non-IBD controls [NC] were assessed levels phosphorylated signal transducers activators transcription [p-STAT] expression genes response an ex vivo inhibitor...
Background Intestinal epithelial cells (IECs) are the first to encounter luminal microorganisms and actively participate in intestinal immunity. We reported that IECs express β-glucan receptor Dectin-1, respond commensal fungi β-glucans. In phagocytes, Dectin-1 mediates LC3-associated phagocytosis (LAP) utilizing autophagy components process extracellular cargo. can mediate of β-glucan-containing particles by non-phagocytic cells. aimed determine whether human phagocytose fungal via LAP....
Abstract Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with metastatic non-small cell lung cancer (NSCLC). However, clinical management is challenging. The PD-L1 biomarker does not optimally guide the choice between ICI monotherapy and combination ICI-chemotherapy, there are currently no biomarkers to predict immune-related adverse events (irAEs). Here, we describe a versatile platform based on plasma proteomics machine learning generating...
Abstract Cancers that are poorly immune infiltrated pose a substantial challenge, with current immunotherapies yielding limited clinical success. Stem-like memory T cells (TSCM) have been identified as subgroup of possess strong proliferative capacity and can expand differentiate following interactions dendritic (DCs). In this study, we explored the pattern expression recently discovered inhibitory receptor poliovirus receptor-related immunoglobulin domain protein (PVRIG) its ligand, ligand...
Patients with inflammatory bowel disease (IBD) treated anti-tumor-necrosis factor-alpha (TNFα) exhibited lower serologic responses one-month following the second dose of COVID-19 BNT162b2 vaccine compared to those not anti-TNFα (non-anti-TNFα) or healthy controls (HCs). We comprehensively analyzed long-term humoral responses, including anti-spike (S) antibodies, serum inhibition, neutralization, cross-reactivity and circulating B cell six months post BNT162b2, in patients IBD stratified by...
Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for cancer. ShRNA screen performed in 42 cell lines identified the centriolar replication factor STIL as essential gene cells. This was verified in-vivo orthotopic human mouse models. depletion by administration of siRNA neutral liposomes resulted robust anti-tumor effect that further enhanced combination with cisplatin. Consistent this finding, extent DNA double...
Abstract Background In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism. The expression of human telomerase reverse transcriptase (hTERT) enables and provides cancer cells with limitless replicative potential. As such, it may serve as an attractive biomarker for oncogenic activity. This study explored whether liquid biopsy that analyses blood derived exosomal hTERT transcript (e‐hTERT‐trans) such in gliomas meningiomas when compared healthy controls....
Background & aims: Janus kinase (JAK) inhibitors modulating JAK-STAT (signal transducers and activators of transcription) signaling pathway, are used for the treatment patients with inflammatory bowel diseases (IBD). We aimed to identify molecular effects JAK inhibition in human intestinal mucosa, considering IBD location phenotype. Methods: Colonic ileal explants from ulcerative colitis (UC), Crohn's disease (CD), or non-IBD controls (NC) were treated ex-vivo inhibitor, tofacitinib....
To evaluate the durability of response 3 months after third BNT162b2 vaccine in adults aged 60 years and older.Prospective cohort study.Single tertiary centre.Healthcare workers/family members ≥60 old who received dose.Blood samples were drawn immediately before (T0), 10-19 days (T1) 74-103 (T2) dose.Anti-spike IgG titres determined using a commercial assay seropositivity was defined as ≥50 arbitrary units (AU)/mL. Neutralising antibody at T2. Adverse events, COVID-19 infections Clinical...
Background: Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed human somatic cells. As such, it has the potential to serve as valid biomarker. Exosomal hTERT mRNA can be detected serum patients with solid malignancies not healthy individuals. We sought evaluate feasibility measuring exosomal transcripts levels lung cancer. Methods: A prospective analysis was determined serum-derived exosomes from 76 stage...
ABSTRACT Introduction Immune checkpoint inhibitors have made a paradigm shift in the treatment of non-small cell lung cancer (NSCLC). However, clinical response varies widely and robust predictive biomarkers for patient stratification are lacking. Here, we characterize early on-treatment proteomic changes blood plasma to gain better understanding resistance. Methods Pre-treatment (T0) (T1) samples were collected from 225 NSCLC patients receiving PD-1/PD-L1 inhibitor-based regimens. Plasma...
<p>Supplemental Figure S3. Antitumor activity of anti-mouse-IL-18BP Ab in mice studies.</p>
<div>Abstract<p>Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- NK-cell activity stimulates IFNγ production. The of naturally blocked by high-affinity endogenous binding protein (IL18BP). IL18BP induced in the tumor microenvironment (TME) response upregulation negative feedback mechanism. In this study, we found that...
<p>Supplemental Figure S1. IL-18BP is a potential soluble immune checkpoint in cancer.</p>
<p>Supplemental Figure S4. Anti-IL-18BP Ab induced immunogenic memory response in E0771 tumor model.</p>