A5063107172- Drug Transport and Resistance Mechanisms
- Genomics and Rare Diseases
- Gout, Hyperuricemia, Uric Acid
- Hemoglobinopathies and Related Disorders
- Trace Elements in Health
- Muscle metabolism and nutrition
- SARS-CoV-2 and COVID-19 Research
- Muscle Physiology and Disorders
- COVID-19 Clinical Research Studies
- Liver Disease Diagnosis and Treatment
- Erythrocyte Function and Pathophysiology
- Metabolism and Genetic Disorders
- PARP inhibition in cancer therapy
- Genetics and Neurodevelopmental Disorders
- Phytochemicals and Medicinal Plants
- Muscle and Compartmental Disorders
- Pharmacological Effects and Toxicity Studies
- Drug-Induced Hepatotoxicity and Protection
- SARS-CoV-2 detection and testing
- Protein purification and stability
- Viral Infectious Diseases and Gene Expression in Insects
- RNA modifications and cancer
- vaccines and immunoinformatics approaches
- Cholesterol and Lipid Metabolism
- Pneumocystis jirovecii pneumonia detection and treatment
HUN-REN Research Centre for Natural Sciences
2018-2025
Semmelweis University
2020-2025
Institute of Molecular Life Sciences
2018-2024
Hungarian Academy of Sciences
2018-2022
During the COVID-19 pandemic, several repurposed drugs have been proposed to alleviate major health effects of disease. These are often applied with analgesics or non-steroid anti-inflammatory compounds, and co-morbid patients may also be treated anticancer, cholesterol-lowering, antidiabetic agents. Since drug ADME-tox properties significantly affected by multispecific transporters, in this study, we examined interactions key human multidrug transporters present tissue barriers strongly...
In this study, we analyzed the potential associations of selected laboratory and anamnestic parameters, as well 12 genetic polymorphisms (SNPs), with clinical COVID-19 occurrence severity in 869 hospitalized patients. The SNPs by qPCR were based on population-wide (GWAS) data previously indicating association COVID-19, additional that have been shown to be important cellular processes also examined. We confirmed pre-existing diabetes found an unexpected between less severe disease loss smell...
In the human ABCG2 multidrug transporter a so called “leucin plug/valve” (aa. L554/L555) has been suggested to determine substrate exit and coupling of drug transport ATPase activity. this work we have analyzed effects selected var-iants in region by expressing these variants both mammalian Sf9 insect cells. We found that cells L554A, L554F, L555F combination L554F/L555F were functional, processed plasma membrane, exhibited activity similar wild-type ABCG2, while L555A...
In the human ABCG2 (ATP Binding Casette transporter G2/BCRP/MXR) multidrug transporter, a so-called “leucin plug/valve” (a.a. L554/L555) has been suggested to facilitate substrate exit and coupling of drug transport ATPase activity. this work, we analyzed effects selected variants in region by expressing these variants, both mammalian Sf9 insect cells. We found that, cells, L554A, L554F, L555F, combination L554F/L555F were functional, processed plasma membrane, exhibited activity similar...
This research shows the detailed comparison of Raman and near-infrared (NIR) spectroscopy as Process Analytical Technology tools for real-time monitoring a protein purification process. A comprehensive investigation application model development NIR was carried out process-related impurity, imidazole, during tangential flow filtration Receptor-Binding Domain (RBD) SARS-CoV-2 Spike protein. The fast spectroscopy-based calibration models achieved using offline data, resulting in low...
To date, there are limited options for severe Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus. As ADP-ribosylation events involved in regulating the life cycle of coronaviruses and inflammatory reactions host; we have, here, assessed repurposing registered PARP inhibitors treatment COVID-19.
The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- endobiotics; thus relatively frequent polymorphic mutant variants population may significantly alter disease conditions pharmacological effects. Low-level or non-functional expression increase individual drug toxicity, reduce cancer resistance, result hyperuricemia gout. In present work we have studied cellular expression, trafficking, function nine naturally occurring ABCG2. A comprehensive...
The ABCG2 membrane protein is a key xeno- and endobiotic transporter, modulating the absorption metabolism of pharmacological agents causing multidrug resistance in cancer. also involved uric acid elimination its impaired function causative gout. Analysis expression erythrocyte membranes healthy volunteers gout patients showed an enrichment lower levels patients. By genetic screening based on expression, we found relatively frequent, novel mutation (ABCG2-M71V), which, according to cellular...
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease and variations in multispecific membrane transporter functions may affect T2DM development, complications or treatment. In this work we have analyzed the potential effects of major polymorphism, Q141K variant ABCG2 T2DM. The protein xeno- endobiotic transporter, affecting drug metabolism playing key role uric acid extrusion. ABCG2-Q141K variant, with reduced expression level function, present 15-35% individuals, depending on...
Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake brain results intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human organoids from induced pluripotent stem cells of healthy subjects CTD patients. Brain donors had reduced compared with those donors. expression neural progenitor cell markers SOX2 PAX6 was CTD-derived organoids, while GSK3β, a key regulator...
GATA1 is a crucial transcription factor involved in hematopoiesis, and mutations this gene are linked to severe hematological disorders, including anemia, thrombocytopenia, Down-syndrome related transient abnormal myelopoiesis (DS-TAM) acute megakaryocytic leukemia (DS- AMKL). Despite significant clinical interest the molecular level characterization of mutations, comprehensive understanding their impact on DNA binding limited. Efforts conduct detailed studies full-length recombinant have...
Gout is a common crystal induced disease of high personal and social burden, characterised by severe arthritis comorbidity if untreated. Impaired function ABCG2 transporter causative in gout may be responsible for renal-overload type hyperuricemia. Despite its importance, there limited information on how clinical parameters correlate with protein expression that genetic changes. Urate 78 gouty patients healthy controls were measured among standardised circumstances from Hungarian population....
In the human ATP2B4 gene, coding for plasma membrane calcium pump PMCA4b, a minor haplotype results in decreased expression of this protein erythroid cells. The presence and consequently reduced PMCA4b have been suggested to affect red blood cell hydration malaria susceptibility. By using dual-luciferase reporter assays, we localized erythroid-specific regulatory region within containing predicted GATA1 binding sites that are affected by SNPs haplotype. Our show that, cells, regulation gene...
Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake brain results intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human organoids from induced pluripotent stem cells of healthy subjects CTD patients. Brain donors had reduced compared with those donors. expression neural progenitor cell markers SOX2 PAX6 was derived organoids, while GSK3β, a key regulator...
Abstract In this study, we analyzed the potential associations of selected laboratory and anamnestic parameters, as well 12 genetic polymorphisms (SNPs), with clinical COVID-19 occurrence severity in 869 hospitalized patients. The SNPs by qPCR were based on population-wide (GWAS) data previously indicating association COVID-19. We confirmed disease several parameters found an unexpected between less severe loss smell taste. most cases, SNP analysis supported earlier results hospitalization...
Abstract In the COVID-19 epidemic, several repurposed drugs have been proposed to alleviate major health effects of disease. These are often applied together with analgesics or non-steroid anti-inflammatory compounds, and co-morbid patients may also be treated anticancer, cholesterol-lowering antidiabetic agents. Since drug ADME-tox properties significantly affected by multispecific transporters, here we examined interactions key human multidrug present in tissue barriers strongly affecting...
The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- endobiotics, contributes to cancer drug resistance development gout. In this work we have analyzed effects selected variants, residing structurally unresolved cytoplasmic region (a.a. 354-367) ABCG2, on function trafficking protein. A cluster four lysines (K357-360) phosphorylation threonine (T362) residue been previously suggested significantly affect cellular fate ABCG2. Here report that...
We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of his-tagged RBD proteins variants were stably engineered into HEK cells secreting protein supernatant, and purification was performed by Ni-chromatography buffer exchange membrane filtration. simplified assay uses single dilutions sera from finger-pricked native blood samples, purified in 96-well plates, chromogenic dye for development....
We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of His-tagged RBD proteins variants were stably engineered into HEK cells secreting protein supernatant, and purification was performed by Ni-chromatography buffer exchange membrane filtration. simplified assay uses single dilutions sera from finger-pricked native blood samples, purified in 96-well plates, chromogenic dye for development....
Abstract Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 virus, is a major global health challenge, as there no efficient treatment for the moderate to severe disease. ADP-ribosylation events are involved in regulating life cycle of coronaviruses and inflammatory reactions host, hence we assessed repurposing registered PARP inhibitors COVID-19. We detected high levels oxidative stress strong PARylation all cell types lungs COVID-19 patients. Interestingly, rucaparib, unlike other...
Abstract Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake brain results intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human organoids from induced pluripotent stem cells of healthy subjects CTD patients. Brain donors had reduced compared with those donors. expression neural progenitor cell markers SOX2 PAX6 was derived organoids, while GSK3β, a key...
Creatine transporter deficiency (CTD) is an X-linked disease caused by mutations in the SLC6A8 gene. The impaired creatine uptake brain results intellectual disability, behavioral disorders, language delay, and seizures. In this work, we generated human organoids from induced pluripotent stem cells of healthy subjects CTD patients. Brain donors had reduced compared with those donors. expression neural progenitor cell markers SOX2 PAX6 was derived organoids, while GSK3β, a key regulator...