A5052368521- Cancer Genomics and Diagnostics
- HIV Research and Treatment
- Fermentation and Sensory Analysis
- Epigenetics and DNA Methylation
- PARP inhibition in cancer therapy
- Protein Structure and Dynamics
- HIV/AIDS drug development and treatment
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Lipid Membrane Structure and Behavior
- CAR-T cell therapy research
- Colorectal Cancer Treatments and Studies
- Ovarian cancer diagnosis and treatment
- Plant Surface Properties and Treatments
- S100 Proteins and Annexins
- Enzyme Production and Characterization
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Viral-associated cancers and disorders
- Nuclear Structure and Function
- Radiation Effects in Electronics
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Plant and fungal interactions
- HIV-related health complications and treatments
- Microencapsulation and Drying Processes
KU Leuven
2011-2024
VIB-KU Leuven Center for Cancer Biology
2019-2024
Flemish Institute for Technological Research
2017-2019
University of Bergen
2016-2017
Clinically relevant immunological biomarkers that discriminate between diverse hypofunctional states of tumor-associated CD8 + T cells remain disputed. Using multiomics analysis cell features across multiple patient cohorts and tumor types, we identified niche–dependent exhausted other types states. in “supportive” niches, like melanoma or lung cancer, exhibited reactivity–driven exhaustion (CD8 EX ). These included a proficient effector memory phenotype, an expanded receptor (TCR)...
Abstract Background Overcoming therapeutic resistance is one of the major hurdles in cancer care. One mechanism contributing to a process which epithelial cells switch mesenchymal state (epithelial-to-mesenchymal transition or EMT). The precise mechanisms driving EMT-mediated have, however, not been elucidated. Results Here, we study ten cell line pairs, for parental lines were made resistant either targeted chemotherapy-based treatment. First, show by miRNA-200 overexpression that treatment...
Abstract Background One-third of cancers activate endogenous synthesis serine/glycine, and can become addicted to this pathway sustain proliferation survival. Mechanisms driving metabolic rewiring remain largely unknown. Methods NKX2–1 overexpressing knockdown/knockout T-cell leukaemia lung cancer cell line models were established study using ChIP-qPCR, immunoblotting, mass spectrometry, invasion assays. Findings therapeutic relevance validated in mouse confirmed patient datasets. Results...
Fragmentation patterns of plasma cell-free DNA (cfDNA) are known to reflect nucleosome positions cell types contributing cfDNA. Based on cfDNA fragmentation patterns, the deviation in footprints was quantified between diagnosed ovarian cancer patients and healthy individuals. Multinomial modeling subsequently applied capture these deviations a per sample footprint score. Validation performed 271 cfDNAs pre-surgically collected from women with an adnexal mass. We confirmed that scores were...
A major therapeutic barrier in melanoma is the coexistence of diverse cellular states marked by distinct metabolic traits. Transitioning from a proliferative to an invasive phenotype coupled with increased ferroptosis vulnerability. However, regulatory circuits controlling susceptibility across cell are unknown. In this work, we identified Apolipoprotein E ( APOE ) as top lipid-metabolism gene segregating MITF high /AXL low proliferative/ferroptosis-resistant invasive/ferroptosis-sensitive...
VIRus Inhibitory Peptide (VIRIP), a 20 amino acid peptide, binds to the fusion peptide (FP) of human immunodeficiency virus type 1 (HIV-1) gp41 and blocks viral entry. VIRIP derivatives with improved antiviral activity have been developed, one those has recently proven effective safe in phase 1/2 clinical trial. Here, molecular dynamics were executed combination mechanics/Poisson-Boltzmann surface area (MM/PBSA) free energy calculations explore binding interaction between FP. A promising...
<h3>Introduction/Background</h3> PAOLA-1/ENGOTov25 trial showed PFS and OS benefit with PARP inhibitor (PARPi) bevacizumab in maintenance treatment of BRCAm homologous recombination deficient (HRD+) ovarian cancer. However, current available HRD tests, including our earlier reported Leuven test (EJC,2023;188:131–9), can still be improved. We developed the new 'Leuven PARPi Benefit Test' as alternative approach to predict PARPi, compared Myriad myChoice CDxPLUS (Myriad test) a training...
Glycoside hydrolases of families 32 (GH32) and 68 (GH68) belong to clan GH-J, containing hydrolytic enzymes (sucrose/fructans as donor substrates) fructosyltransferases acceptor substrates). In GH32 members, some the sugar substrates can also function inhibitors, this regulatory aspect further adding complexity in enzyme functionalities within family. Although 3D structural information becomes increasingly available huge progress has been made on structure-function relationships, it is not...
Although there is a common agreement that hydrophobins and CO2 are responsible for primary gushing of carbonated beverages, the bio-molecular mechanism this phenomenon not well understood. Here, hydrophobin HFBII has been produced, extracted, purified. A test DLS analysis was performed allowed authors to design an MD simulation setup investigate interaction molecules with in time. The results indicate tend aggregate at hydrophobic patch twice as much rest protein. model proposed elucidates...
HIV-1 Rev is the key protein in nucleocytoplasmic export and expression of late viral mRNAs. An important aspect for its function ability to multimerize on these We have recently identified a llama single-domain antibody (Nb190) as first inhibitor targeting multimerization cells. This nanobody potent intracellular that efficiently inhibits production. In order gain insight into Nb190-Rev interaction interface, we performed mutational docking studies map interface between paratope epitope....
Abstract The HIV Rev protein mediates the nuclear export of viral mRNA, and is thereby essential for production late proteins in replication cycle. forms a large organized multimeric protein‐protein complex proper functioning. Recently, three‐dimensional structures dimer tetramer have been resolved provide basis thorough structural analysis binding interaction. Here, molecular dynamics (MD) free energy calculations were performed to elucidate forces thriving dimerization higher order...
The conformationally flexible fusion peptide (FP) of HIV-1 is indispensible for viral infection host cells, due to its ability insert into and tightly couple with phospholipid membranes. There are conflicting reports on the membrane-associated structure FP, solution information limited, yet such a target novel class antiretroviral inhibitors. An ensemble explicit solvent molecular dynamics simulations, initiated from disordered FP (aggregate time ∼30 μs), revealed that while vast majority...
The knowledge of genomic DNA variations in patient samples has a high and increasing value for human diagnostics its broadest sense. Although many methods sensors to detect or quantify these are available under development, the number underlying physico-chemical detection principles is limited. One hybridization sample target versus nucleic acid probes. We introduce novel thermodynamics approach develop framework exploit specific capabilities hybridization, using generic applicable any...
ABSTRACT Tumoural-CD8 + T cells exhibit exhausted or dysfunctional states. Contrary to immunotherapy-responsive exhausted-CD8 cells, the clinical features of dysfunctional-CD8 are disputed. Hence, we conducted large-scale multi-omics and multi-dimensional mapping CD8 cell-states across multiple cancer patient-cohorts. This identified tumour-specific continuum 6 human cancers, partly imprinted by organ-specific immuno-modulatory niches. Herein, melanoma glioblastoma enriched prototypical (CD8...
In Mycobacterium tuberculosis (Mtb) the detection of single nucleotide polymorphisms (SNPs) is high importance both for diagnostics, since drug resistance primarily caused by acquisition SNPs in multiple targets, and epidemiological studies which strain typing performed SNP identification. To provide necessary coverage clinically relevant profiles types, nucleic acid-based measurement techniques must be able to detect a large number potential SNPs. Since Mtb problem pressing many...
Abstract The response regulator PhoP is part of the PhoP/PhoQ two‐component system, which responsible for regulating expression multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating transcriptional function protein a promising strategy developing new agents. There evidence suggesting that phosphorylation‐mediated dimerization regulatory domain essential its function. Disruption or stabilization protein‐protein...
DNA surface-hybridization biosensors utilize the selective hybridization of target sequences in solution to surface-immobilized probes. In this process, is usually assumed be excess, so that its concentration does not significantly vary while hybridizing surface-bound If initially at low concentrations and/or if number probes very large and have high affinity for target, may get depleted. paper we analyze equilibrium kinetics case strong depletion, by extending Langmuir adsorption model. We...