A5012776826- Estrogen and related hormone effects
- Protein Tyrosine Phosphatases
- Synthesis and biological activity
- Computational Drug Discovery Methods
- CRISPR and Genetic Engineering
- ATP Synthase and ATPases Research
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Lung Cancer Research Studies
- Cancer Mechanisms and Therapy
- RNA modifications and cancer
- Cancer Research and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Cancer therapeutics and mechanisms
- Protein Structure and Dynamics
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- CAR-T cell therapy research
- Synthesis and Characterization of Heterocyclic Compounds
- Prostate Cancer Treatment and Research
- PARP inhibition in cancer therapy
- Pluripotent Stem Cells Research
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Genomics and Diagnostics
- Cancer-related molecular mechanisms research
Novartis (Switzerland)
2021-2025
Novartis Institutes for BioMedical Research
2021-2023
Karlsruhe Institute of Technology
2010-2023
Memorial Sloan Kettering Cancer Center
2014-2023
Roche (Switzerland)
2021
Kettering University
2016
FIZ Karlsruhe – Leibniz Institute for Information Infrastructure
2009
Abstract The Hippo pathway is a key growth control that conserved across species. downstream effectors of the pathway, YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif), are frequently activated in cancers to drive proliferation survival. Based on premise sustained interactions between YAP/TAZ TEADs enhanced associate domain) central their transcriptional activities, we discovered potent small-molecule inhibitor (SMI), GNE-7883, allosterically blocks...
Treatment of several types cancer such as lung, breast, prostate, and pancreas has shown notable progresses in the past decades. However, after an initial response, tumors eventually became resistant to chemotherapy. This phenomenon, known chemoresistance, accounts for death most patients. Several studies patients refractory therapy have revealed upregulation molecular chaperone GRP78/Binding Protein, BiP (BiP) both at RNA protein expression level. Furthermore GRP78/BiP relocates cell...
Protein tyrosine phosphatase SHP2 mediates RAS-driven MAPK signaling and has emerged in recent years as a target of interest oncology, both for treating with single agent combination KRAS inhibitor. We were drawn to the pharmacological potential inhibition, especially following initial observation that drug-like compounds could bind an allosteric site enforce closed, inactive state enzyme. Here, we describe identification characterization GDC-1971 (formerly RLY-1971), inhibitor currently...
Activating mutations in the rat sarcoma (RAS) genes HRAS, NRAS and KRAS collectively represent most frequent oncogenic driver human cancer1. They have previously been considered undruggable, but advances past few years led to clinical development of agents that target KRAS(G12C) KRAS(G12D) mutants, yielding promises therapeutic responses at tolerated doses2. However, selectively NRAS(Q61*) mutants (* represents 'any'), second-most-frequent melanoma, are still lacking. Here we identify SHOC2,...
Abstract BACKGROUND AGR2 is a member of the endoplasmatic reticulum protein disulphide isomerase gene family implicated in tumor metastasis. Its expression pattern, function, and utility as marker remains to be further investigated. METHODS Using real‐time RT‐PCR immunohistochemistry, changes different stages were explored microdissected samples. transcript level urine sediments was scrutinized for suitability marker. androgen regulation function analyzed cellular prostate cancer models....
Background MicroRNAs (miRNAs) are potential biomarkers in various malignancies. We aim to characterize miRNA expression intrahepatic cholangiocarcinoma (ICC) and identify circulating plasma miRNAs with diagnostic prognostic utility. Methods Using deep-sequencing techniques, between tumor samples non-neoplastic liver parenchyma were compared. Overexpressed measured from an independent cohort of patients using RT-qPCR compared that healthy volunteers. The discriminatory ability the evaluated...
The Bag (Bcl-2 associated athanogene) family of proteins consists 6 members sharing a common, single-copied domain through which they interact with the molecular chaperone Hsp70. Bag5 represents an exception in since it 5 domains covering whole protein. like Bag1 and Bag3 have been implicated tumor growth survival but is not known whether also exhibits this function.Bag5 mRNA protein expression levels were investigated prostate cancer patient samples using real-time PCR immunoblot analyses....
Abstract Small cell lung cancer (SCLC) has limited therapeutic options and an exceptionally poor prognosis. Understanding the oncogenic drivers of SCLC may help define novel targets. Recurrent genomic rearrangements have been identified in SCLC, most notably in-frame gene fusion between RLF MYCL found up to 7% predominant ASCL1-expressing subtype. To explore role this oncogenesis tumor progression, we used CRISPR/Cas9 somatic editing generate a Rlf–Mycl-driven mouse model SCLC. RLF–MYCL...
The molecular chaperone GRP78/BiP is a key regulator of protein folding in the endoplasmic reticulum, and it plays pivotal role cancer cell survival chemoresistance. Inhibition its function has therefore been an important strategy for inhibiting tumor growth therapy. Previous efforts to achieve this goal have used peptides that bind conjugated pro-drugs or cell-death-inducing sequences. Here, we describe peptide induces prostate death without need any conjugating This sequence derived from...
Background: Divarasib, a covalent inhibitor targeting the Kirsten rat sarcoma virus oncogene homologue glycine-to-cysteine mutation at position 12 (KRAS G12C), is currently in clinical development for Non Small Cell Lung Cancer (NSCLC) treatment, with various combination partners, such as Src homology region 2 domain-containing phosphatase-2 (SHP2) migoprotafib. A quantitative systems pharmacology (QSP) model essential to quantitatively assess single-agent and pharmacodynamic (PD) effects...
Abstract RIT1 is a RAS-family GTPase that mutated in 2.4% and amplified up to 14% of lung adenocarcinoma patients. Yet, the oncogenic potential lungs not completely understood. Many patients with alterations are considered ‘oncogene-negative’, hence they eligible for any targeted therapy clinic. The role cancer has been historically understudied due lack vitro vivo models harboring alterations. In this study, we generated first murine model RIT1M90I-mutant cancer. We found RIT1M90I was...
Abstract The KIAA1549-BRAF (KB) fusion is a prevalent genetic event in two distinct central nervous system tumors: pilocytic astrocytomas (PAs) and diffuse leptomeningeal glioneuronal tumors (DLGNTs). This chromosomal rearrangement, consisting of 2 Mbp tandem duplication at 7q34, results the formation protein absent normal cells. KB has been described to dimerize BRAF kinase RAS-independent manner, leading constitutive activation MAPK pathway promoting tumorigenesis. Despite its...
The pro-oncogenic activities of estrogen receptor alpha (ERα) drive breast cancer pathogenesis. Endocrine therapies that impair the production or action ERα are therefore used to prevent primary disease metastasis. Although recent successes with degraders have been reported, there is still need develop further antagonists additional properties for therapy. We previously described a benzothiazole compound A4B17 inhibits proliferation androgen receptor–positive prostate cells by disrupting...
To cite this article: Obiri DD, Flink N, Maier JV, Neeb A, Maddalo D, Thiele W, Menon Stassen M, Kulkarni RA, Garabedian MJ, Barrios AM, Cato ACB. PEST‐domain‐enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice. Allergy 2012; 67 : 175–182. Abstract Background: (PEP) is a protein exclusively expressed hematopoietic cells. It potent negative regulator T‐cell receptor signalling that acts on receptor‐coupled kinases. also mast cell positively regulated by...
Off-target editing is one of the main safety concerns for use CRISPR-Cas9 genome in gene therapy. These unwanted modifications could lead to malignant transformation, which renders tumorigenicity assessment therapy products indispensable. In this study, we established two vitro transformation assays, soft agar colony-forming assay (SACF) and growth low attachment (GILA) as alternative methods evaluation genome-edited cells. Using a CRISPR-Cas9-based approach transform immortalized MCF10A...
This protocol describes a method to measure the enzymatic activity of molecular chaperones in cell-based system and possible effects compounds with inhibitory/stimulating activity. Molecular are proteins involved regulation protein folding1 have crucial role promoting cell survival upon stress insults like heat shock2, nutrient starvation exposure chemicals/poisons3. For this reason found be events tumor development, chemioresistance cancer cells4 as well neurodegeneration5. Design small...