A5087140172- Drug Transport and Resistance Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- RNA Interference and Gene Delivery
- Advanced Drug Delivery Systems
- Amino Acid Enzymes and Metabolism
- Radiopharmaceutical Chemistry and Applications
- Glioma Diagnosis and Treatment
- Diabetes Treatment and Management
- Cell Adhesion Molecules Research
- Pharmacogenetics and Drug Metabolism
- Medical Imaging and Pathology Studies
- Biochemical and Structural Characterization
- Advanced biosensing and bioanalysis techniques
- Peptidase Inhibition and Analysis
- Lipoproteins and Cardiovascular Health
- Biopolymer Synthesis and Applications
- HIV/AIDS drug development and treatment
- Clostridium difficile and Clostridium perfringens research
- Lipid Membrane Structure and Behavior
- Immunotherapy and Immune Responses
- Hormonal and reproductive studies
- Galectins and Cancer Biology
- Cardiac electrophysiology and arrhythmias
- Mass Spectrometry Techniques and Applications
University Hospital Heidelberg
2016-2025
Heidelberg University
2016-2025
Novo Nordisk (Denmark)
2024
German Center for Infection Research
2019-2023
German Cancer Research Center
2015-2016
Lankenau Medical Center
1921
Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) multiplexed immunofluorescence 122) on chemo-naive postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) define impact neoadjuvant chemotherapy. Transcriptome analysis combined high-resolution mapping whole-tissue...
Background/Objectives: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake regulating intrahepatic availability statins, increases systemic exposure co-administered statins. This interaction could raise risk myopathy. We hypothesized that drug between BA statins be mitigated by staggered administration. Methods: was single-centre, open-label,...
Abstract Background Pediatric low-grade gliomas (pLGG) are the most common pediatric central nervous system tumors, with driving alterations typically occurring in MAPK pathway. The ERK1/2 inhibitor ulixertinib (BVD-523) has shown promising responses adult patients mitogen-activated protein kinase (MAPK)-driven solid tumors. Methods We investigated antitumoral activity of monotherapy as well combination MEK inhibitors (MEKi), BH3-mimetics, or chemotherapy pLGG. Patient-derived pLGG models...
Purpose: Targeted therapies are regarded as promising approaches to increase 5-year survival rate of head and neck squamous cell carcinoma (HNSCC) patients.Experimental design: For the selection carcinoma-specific peptides membrane proteome HNO97 tumor cells fractionated by ProteomeLab PF2D system corresponding were deployed for an alternating biopanning using a sunflower trypsin inhibitor1-based phage display (SFTI8Ph) library. Stability, binding properties affinity novel candidates...
α<sub>v</sub>β<sub>6</sub> integrin is overexpressed by several carcinomas and thus considered a target for diagnostic imaging anticancer therapies. Recently, we presented the integrin-binding peptide SFITGv6 as novel potential tracer targeted therapy of integrin–positive carcinomas. Here, analyzed affinity specificity 5 native integrin–specific binders in comparison to SFITGv6. <b>Methods:</b> Sunflower trypsin inhibitor 1 (SFTI1)–based peptides containing arginine-glycine-aspartic acid...
Lipid-based drug delivery systems can be surface-modified by lipid conjugates of the substance in question. The most important modifications include arginine-rich cell-penetrating peptides (CPP). A toxicokinetic evaluation these is im-portant during preclinical and clinical development formulations. Due to their amphiphilic properties high number basic amino acid residues, CPP exhibit difficult characteristics regard plasma bioanalysis with LC-MS/MS instruments. These especially challenging...
Abstract Despite the high medical need for oral peptide delivery, instability in gastrointestinal tract and low mucosal permeation still impede this preferred route of administration. Herein, a liposomal nanocarrier combining two self‐reliant strategies to overcome these delivery barriers is reported. This approach enables design system with synergistic properties: tetraether lipids derived from archaea are incorporated into liposomes provide particles stability required traverse stomach....
The solute carrier L-type amino acid transporter 1 (LAT-1/SLC7A5) is a viable target for drug delivery to the central nervous system (CNS) and tumors due its high abundance at blood-brain barrier in tumor tissue. LAT-1 only localized on cell surface as heterodimer with CD98, which not required function. To support future CNS drug-delivery development based targeting, we established an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) assay stable isotopically...
Compared to rifampicin (600 mg/day), standard doses of rifabutin (300 mg/day) have a lower risk drug-drug interactions due induction cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (Pgp/ABCB1) mediated by the pregnane X receptor (PXR). However, clinical comparisons with equal rifamycin in vitro experiments respecting actual intracellular concentrations are lacking. Thus, genuine pharmacological differences and potential molecular mechanisms discordant perpetrator effects unknown....
Abstract Oral delivery of peptides is severely limited by their instability and poor absorption in the gastrointestinal tract. In contrast to coadministration strategies using medium‐chain fatty acids, which have recently gained regulatory approval with low oral bioavailabilities ≤ 1% (Rybelsus Mycapssa), efforts clinically implement systems based on nanocarriers not been successful date. The approved drug‐delivery formulations show fairly accurate correlation between clinical results...
Aim: Pharmacokinetics after oral microdosing of the anticipated CYP2D6 substrate yohimbine and its metabolite 11-OH-yohimbine is potentially useful for drug–drug interaction trials profiling enzyme activity. Materials & methods: We developed an ultrasensitive ultra performance liquid chromatography coupled to tandem mass spectrometry assay quantification main in plasma with a linear calibration range 5–2500 pg/ml validated it according US FDA's EMA's guidelines. Sample preparation was...
Multiple therapeutic monoclonal antibodies (mAbs) are currently under development or in (pre)clinical study phases to reach regulatory approval. Among these, a new mAb against herpes simplex virus, HDIT101, was recently tested healthy volunteers during phase I clinical trial (first-in-human, dose escalation). In the frame of pharmacokinetic evaluation this therapy, mass spectrometric (MS)-based method developed for quantification HDIT101 human plasma using liquid chromatography coupled...
Lipid-based drug delivery systems can be surface modified by lipid-conjugates of the pertinent substance. Prominent modifica-tions include arginine-rich cell-penetrating peptides (CPP). Toxicokinetic evaluation these is important during pre- and clinical development drug-delivery formulations. Due to their amphiphilic character high number basic amino acid residues, CPP exhibit challenging characteristics in regard plasma bioanalysis with LC-MS/MS instruments. These especially chromatography...
Aim: An ultrasensitive UPLC–MS/MS assay for liraglutide was developed and validated according to US FDA EMA guidelines applied the quantification of plasma concentrations after intravenous, nasal oral administration beagle dogs. Results: Liraglutide isolation performed with a combined protein precipitation solid-phase extraction protocol. The calibrated concentration range 0.1–200 ng/ml linear correlation coefficients >0.998. Precise analysis achieved through utilization an isotopically...
Abstract The most important dose-limiting factor of the anthracycline idarubicin is high risk cardiotoxicity, in which secondary alcohol metabolite idarubicinol plays an role. It not yet clear enzymes are for formation and inhibitors might be suitable to suppress this metabolic step thus would promising concomitant drugs reduce idarubicin-associated cardiotoxicity. We, therefore, established validated a mass spectrometry method intracellular quantification investigated different cell lines...
Abstract Tacrolimus is metabolized by cytochrome P450 3A (CYP3A) and susceptible to interactions with the CYP3A P‐glycoprotein inducer St. John's Wort (SJW). isozymes are predominantly expressed in small intestine liver. Prolonged‐release tacrolimus (PR‐Tac) largely absorbed distal intestinal segments less inhibition. The effect of induction SJW unknown. In this randomized, crossover trial, 18 healthy volunteers received single oral doses (immediate‐release [IR]‐Tac or PR‐Tac, 5 mg each)...
Metformin is the gold standard substrate for evaluating potential inhibitors of organic cation transporters (OCTs). Here, we established a UPLC-MS/MS assay to quantify metformin in cell pellets with range 0.05-50 ng/mL using 6-deuterated as an internal standard. We used ion-pairing chromatographic approach heptafluorobutyric acid, making use reverse-phase column, and overcame associated ion-suppression via previously post-column injection aqueous ammonia. The was validated according Food...