A5021999151- Glycosylation and Glycoproteins Research
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Cellular transport and secretion
- Neurological diseases and metabolism
- Endoplasmic Reticulum Stress and Disease
- Amino Acid Enzymes and Metabolism
- Neonatal Health and Biochemistry
- Genomics and Rare Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Pancreatic function and diabetes
- Folate and B Vitamins Research
- Microtubule and mitosis dynamics
- Carbohydrate Chemistry and Synthesis
- Transgenic Plants and Applications
- Genetics, Aging, and Longevity in Model Organisms
- Biochemical Acid Research Studies
- Hereditary Neurological Disorders
- HIV/AIDS drug development and treatment
- Insect Resistance and Genetics
- Plant biochemistry and biosynthesis
- Immunodeficiency and Autoimmune Disorders
- Gut microbiota and health
- Genetics and Neurodevelopmental Disorders
- Microbial Metabolic Engineering and Bioproduction
VIB-KU Leuven Center for Cancer Biology
2021-2024
University College London
2016-2024
Great Ormond Street Hospital
2019-2024
KU Leuven
2024
Institute of Child Health
2019
Medizinische Hochschule Hannover
2012
Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, bacterium E. coli and nematode C. elegans, we performed three-way high-throughput screens that unraveled complexity underlying host-microbe-drug interactions. report microbes can bolster or suppress effects fluoropyrimidines...
The tendency for proteins to form aggregates is an inherent part of every proteome and arises from the self-assembly short protein segments called aggregation-prone regions (APRs). While posttranslational modifications (PTMs) have been implicated in modulating aggregation, their direct role APRs remains poorly understood. In this study, we used a combination proteome-wide computational analyses biophysical techniques investigate potential involvement PTMs aggregation regulation. Our findings...
Dolichol is a lipid critical for N-glycosylation as carrier activated sugars and nascent oligosaccharides. It commonly thought to be directly produced from polyprenol by the enzyme SRD5A3. Instead, we found that dolichol synthesis requires three-step detour involving additional metabolites, where SRD5A3 catalyzes only second reaction. The first third steps are performed DHRSX, whose gene resides on pseudoautosomal regions of X Y chromosomes. Accordingly, report pseudoautosomal-recessive...
Objective To identify disease‐causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods We performed genome‐wide sequencing, homozygosity mapping, segregation analysis for novel gene discovery. used circular dichroism to show secondary structure changes isothermal titration calorimetry investigate the impact of on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays mass...
Abstract CAD is a large, 2225 amino acid multienzymatic protein required for de novo pyrimidine biosynthesis. Pathological variants cause developmental and epileptic encephalopathy which highly responsive to uridine supplements. deficiency difficult diagnose because symptoms are nonspecific, there no biomarker, the has over 1000 known variants. To improve diagnosis, we assessed pathogenicity of 20 unreported missense using growth complementation assay that identified 11 pathogenic in seven...
Abstract ALDH7A1 deficiency is an epileptic encephalopathy whose seizures respond to treatment with supraphysiological doses of pyridoxine. It arises as a result damaging variants in ALDH7A1, gene the lysine catabolism pathway. α‐Aminoadipic semialdehyde (α‐AASA) and Δ 1 ‐piperideine‐6‐carboxylate (P6C), which accumulate because block pathway, are diagnostic biomarkers for this disorder. Recently, it has been reported that 6‐oxo‐pipecolic acid (6‐oxo‐PIP) also accumulates urine, CSF plasma...
We report the development of a rapid, simple, and robust LC–MS/MS-based enzyme assay using dried blood spots (DBS) for diagnosis pyridox(am)ine 5′-phosphate oxidase (PNPO) deficiency (OMIM 610090). PNPO leads to potentially fatal early infantile epileptic encephalopathy, severe developmental delay, other features neurological dysfunction. However, upon prompt treatment with high doses vitamin B6, affected patients can have normal outcome. Prognosis these is therefore reliant rapid diagnosis....
Abstract The transmembrane domain recognition complex (TRC) pathway is required for the insertion of C-terminal tail-anchored (TA) proteins into lipid bilayer specific intracellular organelles such as endoplasmic reticulum (ER) membrane. In order to facilitate correct insertion, (consisting BAG6, GET4 and UBL4A) must first bind TA then GET3 (TRC40, ASNA1), which chaperones protein ER Subsequently, GET1 (WRB) CAML form a receptor that enables integration within bilayer. We report an...
To assess the pyridoxal 5'-phosphate (PLP) content and stability of extemporaneous PLP liquids prepared from dietary supplements used for treatment vitamin B6 -dependent epilepsy.Pyridoxal were in accordance with guidelines given to patients marketed 50 mg capsules tablets. The its evaluated under conditions resembling clinical setting using reverse phase HPLC mass spectrometry.Pyridoxal most extemporaneously was found be different expected amount (~16-60 mg). Most these stable at room...
Abstract Recently, a disorder caused by the heterozygous de novo c.1267C>T (p.R423*) substitution in SLC37A4 has been described. This causes mislocalization of glucose‐6‐phosphate transporter to Golgi leading congenital glycosylation type II (SLC37A4‐CDG). Only one patient reported showing liver disease that improved with age and mild dysmorphism. Here we report second CDG same mutation thereby confirming pathogenicity this variant expanding clinical picture 1 diabetes, severe scoliosis,...
Abstract Glycosylation-deficient Chinese hamster ovary (CHO) cell lines have been instrumental in the discovery of N-glycosylation machinery. Yet, molecular causes glycosylation defects Lec5 and Lec9 mutants elusive, even though for both a defect dolichol formation from polyprenol was previously established. We recently found that synthesis occurs three steps consisting conversion to polyprenal by DHRSX, reduction dolichal SRD5A3 dolichol, again DHRSX. This led us investigate defective...
ABSTRACT The tendency for proteins to form aggregates is an inherent part of every proteome and arises from the self-assembly short protein segments called aggregation-prone regions (APRs). While post-translational modifications (PTMs) have been implicated in modulating aggregation, their direct role APRs remains poorly understood. In this study, we used a combination proteome-wide computational analyses biochemical techniques investigate potential involvement PTMs aggregation regulation....
Polyneuropathies are amongst the most common neurological conditions worldwide affecting over 20 million people. However, 40% of patients with primary polyneuropathies have no disease-causing mutation identified. We investigated gene-negative using a combination whole genome sequencing, homozigosity mapping and segregation analysis. Pathogenicity was confirmed via enzymatic assays mass spectroscopy on recombinant protein patient-derived fibroblasts, plasma erythrocytes. used circular...
Polyneuropathies are amongst the most common neurological conditions worldwide affecting over 20 million people. However, 40% of patients with primary polyneuropathies have no disease-causing mutation identified. We investigated gene-negative using a combination whole genome sequencing, homozygosity mapping and segregation analysis. Pathogenicity was confirmed via enzymatic assays mass spectroscopy on recombinant protein patient-derived fibroblasts, plasma erythrocytes. used circular...