- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Solar Thermal and Photovoltaic Systems
- Neuropeptides and Animal Physiology
- Congenital Diaphragmatic Hernia Studies
- T-cell and B-cell Immunology
- Intestinal Malrotation and Obstruction Disorders
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Photovoltaic System Optimization Techniques
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Immune cells in cancer
- Gastrointestinal disorders and treatments
- Receptor Mechanisms and Signaling
- Neuroblastoma Research and Treatments
- Esophageal and GI Pathology
- Microtubule and mitosis dynamics
- RNA Interference and Gene Delivery
- Congenital Anomalies and Fetal Surgery
- Childhood Cancer Survivors' Quality of Life
- Pediatric Hepatobiliary Diseases and Treatments
- Ubiquitin and proteasome pathways
Hebrew University of Jerusalem
2014-2024
Hebrew College
2004-2023
Hypertension Institute
2023
University of Colorado Anschutz Medical Campus
2023
Ludwig-Maximilians-Universität München
2012-2022
Essen University Hospital
2021-2022
München Klinik
2018-2019
University of Bern
1995-2019
Bayer (Germany)
2000-2019
Klinik und Poliklinik für Psychosomatik und Psychotherapie
2019
Reprogrammed glucose metabolism of enhanced aerobic glycolysis (or the Warburg effect) is known as a hallmark cancer. The roles long noncoding RNAs (lncRNA) in regulating cancer at level both and gluconeogenesis are mostly unknown. We previously showed that lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) acts proto-oncogene hepatocellular carcinoma (HCC). Here, we investigated role MALAT1 metabolism. upregulated expression glycolytic genes downregulated gluconeogenic...
The ubiquitin-related SUMO-1 molecule has been shown recently to modify covalently a number of cellular proteins including IκBα. modification was found antagonize IκBα ubiquitination and protect it from degradation. Here we identify the transcription factors c-Jun p53, two well known targets ubiquitin, as new substrates for both in vitro vivo. In contrast preferentially single lysine residue (Lys-229), abrogation does not compromise its ubiquitination. Activation Jun NH2-terminal kinases,...
Abstract Genetic engineering of T cells for adoptive transfer by introducing a tumor-targeting chimeric antigen receptor (CAR) is new approach to cancer immunotherapy. A challenge the field define cell surface molecules that are both preferentially expressed on tumor and can be safely targeted with cells. The orphan tyrosine kinase ROR1 candidate target T-cell therapy CAR-modified (CAR-T cells) because it many lymphatic epithelial malignancies has putative role in survival. isoform...
Significance The Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD-2) complex recognizes lipopolysaccharide (LPS) on Gram-negative bacteria to induce an innate immune response. Neoseptins, chemically synthesized peptidomimetics that bind and activate the mouse TLR4 (mTLR4)/MD-2 independent of LPS, were discovered through unbiased screening reverse genetic studies, improved by chemical modification. NMR X-ray crystallography TLR4/MD-2/Neoseptin-3 determined mechanism which...
Abstract Purpose: The identification and vetting of cell surface tumor-restricted epitopes for chimeric antigen receptor (CAR)–redirected T-cell immunotherapy is the subject intensive investigation. We have focused on CD171 (L1-CAM), an abundant molecule neuroblastomas and, specifically, glycosylation-dependent tumor-specific epitope recognized by CE7 monoclonal antibody. Experimental Design: expression was assessed IHC using mAb in tumor microarrays primary, metastatic, recurrent...
IL-17-producing CD8+ (Tc17) cells are enriched in active lesions of patients with multiple sclerosis (MS), suggesting a role the pathogenesis autoimmunity. Here we show that amelioration MS by dimethyl fumarate (DMF), mechanistically elusive drug, associates suppression Tc17 cells. DMF treatment results reduced frequency Tc17, contrary to Th17 cells, and decreased ratio regulators RORC-to-TBX21, along shift towards cytotoxic T lymphocyte gene expression signature from patients....
Abstract Background Children with hepatoblastoma (HB) are at risk of sarcopenia due to immobility, chemotherapy, and malnutrition. We hypothesized that children HB have a low preoperative total psoas muscle area (tPMA), reflecting sarcopenia, which negatively impacts outcome. Procedure Retrospective study (1‐10 years) treated large university children's hospital from 2009 2018. tPMA was measured as the sum right left (PMA) intervertebral disc levels L3‐4 L4‐5. z ‐Scores were calculated using...
Significance Statement This study sheds light on the central role of adenine nucleotide translocase 2 (ANT2) in pathogenesis obesity-induced CKD. Our data demonstrate that ANT2 depletion renal proximal tubule cells (RPTCs) leads to a shift their primary metabolic program from fatty acid oxidation aerobic glycolysis, resulting mitochondrial protection, cellular survival, and preservation function. These findings provide new insights into underlying mechanisms CKD have potential be translated...
Abstract Senescent cells within tumors and their stroma exert complex pro- anti-tumorigenic functions. However, the identities traits of these cells, potential for improving cancer therapy through targeting, remain poorly characterized. Here, we identify a senescent subset previously-defined cancer-associated fibroblasts (CAFs) in pancreatic ductal adenocarcinomas (PDAC) premalignant lesions mice humans. CAFs isolated from mouse humans expressed elevated levels immune-regulatory genes....
A recessive phenotype called spin (spontaneous inflammation) was induced by N -ethyl- -nitrosourea (ENU) mutagenesis in C57BL/6J mice. Homozygotes display chronic inflammatory lesions affecting the feet, salivary glands and lungs, antichromatin antibodies. They are immunocompetent show enhanced resistance to infection Listeria monocytogenes . TLR-induced TNF IL-1 production normal macrophages derived from The autoinflammatory of mice is fully suppressed compound homozygosity for Myd88 poc ,...
Detection of non-self RNA by TLRs within endosomes and retinoic acid-inducible gene I (RIG-I)-like helicases in the cytosol is central to mammalian antiviral immunity. In this study, we used pathway-specific agonists targeted delivery address immunorecognition primary human immune cells. Within PBMC, plasmacytoid dendritic cells (pDC) monocytes were found be responsible for IFN-alpha production upon RNA. The mechanisms recognition pDC distinct. pDC, ssRNA dsRNA oligonucleotides was...
Plasma cells (PCs) are responsible for the secretion of antibodies. The development fully functional PCs relies on activation inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP-1) arm unfolded response (UPR). XBP-1-deficient secrete antibodies poorly and exhibit distensions endoplasmic reticulum (ER). kinase mammalian target rapamycin (mTOR) promotes anabolic activities is negatively regulated by tuberous sclerosis complex (TSC). Deletion TSC1 renders mTOR hyperactive. To explore...
Stimulation of TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases promotes tumor progression through numerous cellular mechanisms. cognate ligands GAS6 PROS1 (for TYRO3 are secreted by host immune cells, an interaction which may support progression. Here, we revealed unexpected antimetastatic role for myeloid-derived PROS1: suppressing metastatic potential in lung breast models. Pros1 deletion myeloid cells led to increased metastasis, independent primary infiltration. PROS1-cKO bone...
Congenital cytomegalovirus (cCMV) is the most common intrauterine infection, leading to infant neurodevelopmental disabilities. An improved knowledge of correlates protection against cCMV needed guide prevention strategies. Here, we employ an ex vivo model human CMV (HCMV) infection in decidual tissues women with and without preconception immunity CMV, recapitulating nonprimary vs. primary at authentic maternofetal transmission site. We show that exhibit intrinsic resistance HCMV, mounting a...
Upon exposure to stress signals, the p53 tumor suppressor protein is stabilized and induces growth suppression. activities are efficiently inhibited by Mdm2 oncoprotein through an autoregulatory feedback loop. In addition, promotes degradation, thereby terminating its inhibitory signal. Hence, exerts effects during interval between activation subsequent inhibition Mdm2. Modulation of this regulatory proteins may determine extent duration activity. Recent studies have shown that c-Abl...
Using [14C]palmitoyl-CoA as donor and deacylated (fatty acid-free) structural proteins of Semliki Forest virus exogenous acceptors, palmitic acid was incorporated into polypeptide in a cell-free system with microsomes baby hamster kidney cells, chicken embryo fibroblasts, rat liver cells. Out the four viral (E1, E2, E3, C) only E1 becomes acylated enzymatically. The protein bound fatty acids vitro product are resistant to detergents organic extractions but can be released hydroxylamine thus...