A5067760174- Acute Myeloid Leukemia Research
- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- Protein Degradation and Inhibitors
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Pancreatic and Hepatic Oncology Research
- PI3K/AKT/mTOR signaling in cancer
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Lung Cancer Treatments and Mutations
- Cancer, Hypoxia, and Metabolism
- Gastrointestinal Tumor Research and Treatment
- Cancer Cells and Metastasis
- Glioma Diagnosis and Treatment
- Gene expression and cancer classification
- Cell Adhesion Molecules Research
- Microbial Natural Products and Biosynthesis
- Cell Image Analysis Techniques
- Melanoma and MAPK Pathways
- Multiple Myeloma Research and Treatments
- Advanced Biosensing Techniques and Applications
University of Copenhagen
2017-2025
Institute for Molecular Medicine Finland
2015-2024
University of Helsinki
2015-2024
Novo Nordisk Foundation
2019-2024
Copenhagen University Hospital
2024
Rigshospitalet
2024
Finland University
2013-2022
University of Turku
2013-2019
University of Miami
2019
Sylvester Comprehensive Cancer Center
2019
T-cell large granular lymphocytic leukemia is a rare lymphoproliferative disorder characterized by the expansion of clonal CD3+CD8+ cytotoxic T lymphocytes (CTLs) and often associated with autoimmune disorders immune-mediated cytopenias.
Rational design of multi-targeted drug combinations is a promising strategy to tackle the resistance problem for many complex disorders. A combination usually classified as synergistic or antagonistic, depending on deviation observed response from expected effect calculated based reference model non-interaction. The existing models were proposed originally low-throughput experiments, which make assumptions often incompatible with interaction patterns across various dose pairs that are...
We carried out a systematic evaluation of target selectivity profiles across three recent large-scale biochemical assays kinase inhibitors and further compared these standardized bioactivity with data reported in the widely used databases ChEMBL STITCH. Our comparative revealed relative benefits potential limitations among types, as well pinpointed biases database curation processes. Ignoring such issues heterogeneity representation may lead to biased modeling drugs' polypharmacological...
We present an individualized systems medicine (ISM) approach to optimize cancer drug therapies one patient at a time. ISM is based on (i) molecular profiling and ex vivo sensitivity resistance testing (DSRT) of patients' cells 187 oncology drugs, (ii) clinical implementation predicted be effective, (iii) studying consecutive samples from the treated patients understand basis resistance. Here, application 28 with acute myeloid leukemia (AML) uncovered five major taxonomic drug-response...
Abstract We developed a systematic algorithmic solution for quantitative drug sensitivity scoring (DSS), based on continuous modeling and integration of multiple dose-response relationships in high-throughput compound testing studies. Mathematical model estimation interpolation makes the approach robust against sources technical variability widely applicable to various experimental settings, both cancer cell line models primary patient-derived cells. Here, we demonstrate its improved...
Abstract Allele-specific signaling by different KRAS alleles remains poorly understood. The KRASG12R mutation displays uneven prevalence among cancers that harbor the highest occurrence of mutations: It is rare (∼1%) in lung and colorectal cancers, yet relatively common (∼20%) pancreatic ductal adenocarcinoma (PDAC), suggesting context-specific properties. We evaluated whether functionally distinct from more KRASG12D- or KRASG12V-mutant proteins (KRASG12D/V). found KRASG12D/V but not drives...
Abstract We generated ex vivo drug-response and multiomics profiling data for a prospective series of 252 samples from 186 patients with acute myeloid leukemia (AML). A functional precision medicine tumor board (FPMTB) integrated clinical, molecular, application in clinical treatment decisions. Actionable drugs were found 97% AML, the recommendations clinically implemented 37 relapsed or refractory patients. report 59% objective response rate individually tailored therapies, including 13...
The broad research use of organoids from high-grade serous ovarian cancer (HGSC) has been hampered by low culture success rates and limited availability fresh tumor material. Here, we describe a method for generation long-term expansion HGSC with efficacy markedly improved over previous reports (53% vs. 23%-38%). We established cryopreserved material, demonstrating the feasibility using viably biobanked tissue organoid derivation. Genomic, histologic, single-cell transcriptomic analyses...
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Previous work indicates that RhoA phosphorylation on Ser188 by cAMP or cGMP-dependent kinases inhibits its activity. However, these studies lacked the possibility to directly study phosphorylated activity in vivo. Therefore, we created proteins containing phosphomimetic residues place of cAMP/cGMP-dependent kinase site. substitution did not affect Rho guanine nucleotide exchange factor, GTPase activating protein, geranylgeranyl transferase vitro but promoted binding guanine-dissociation...
The mouse cell line GD25, which lacks expression of the beta 1 family integrin heterodimers due to disruption subunit gene, was used for full-length cDNA coding splice variant A subunit. In a stably transformed clone (GD25-beta 1A), expressed protein found form functional heterodimeric receptors together with subunits alpha 3, 5, and 6. Both GD25 GD25-beta 1A attached fibronectin formed focal contacts contained v but no detectable 5 1A. presence GRGDS peptide allowed locate cultured on...