In this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction.

Lipid signaling is an essential biological event/process in a plethora of pathophysiological conditions. The underlying idea of this thesis is that many of the roles and the complex interplay of the individual signaling lipids in inflammatory processes and related conditions in health and disease is…

There is a need for alternative methods to replace, reduce and refine (3R) animal experimentation. Combining experimental data from high-throughput in vitro studies with in silico modeling is a promising approach to unravel the effect of chemicals on living cells and to gain a better understanding of…

Promotores:Th.J.C. van Berkel, M. van Eck

Accurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have supported the PK prediction of the CNS target sites and the translation of PK data between species and between…

Promotor: W. Jiskoot, Co-promotor: A. Kros

This thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies delved into the application of proteochemometrics (PCM), a machine learning technique that can be used to…

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

With an emphasis on developing novel miktoarm star polymers termed PeptoMiktoStars, this thesis leverages asymmetric polymeric polypept(o)ide frameworks to advance their effectiveness in delivering hydrophobic drugs and nucleic acids.

In this research project, we aimed to obtain more insight in the role of mast cells in the immune driven disorders rheumatoid arthritis and atherosclerosis.

Despite being the second largest transmembrane protein family after GPCRs, the SLC superfamily has only gained significant attention in early drug development over the past decade.

In this thesis, we developed new ways to use a technique called electroextraction (EE) to extract charged molecules from one liquid into another using an electric field.

Pericytes, the mural cells of blood microvessels, are important regulators of vascular morphogenesis and function that have been postulated to mechanically control microvascular diameter through as yet unknown mechanisms.

Explaining treatment response variability between and within patients can support treatment and dosing optimization, to improve treatment of individual patients.

The ideas underlying this thesis are that lipidomics may improve the diagnosis of liver metabolic diseases, and can provide further insights into the underlying pathophysiology of these diseases.

The challenge of achieving fast quantification in metabolomics is the presence of severe matrix effects during the MS analysis of complex samples.

Metabolomics has the potential to play a pivotal role in understanding disease onset and progression, and ultimately personalized treatments. One of its major challenges is its large-scale implementation, which is necessary to deal with the high variability of the metabolome. In this work we have developed…

Promotor: B. van de Water, Co-promotor: E.H.J. Danen

Metabolomics is a powerful tool that can provide a comprehensive insight into the complexity of human biology and the pathophysiology of diseases. By analyzing the metabolome, which refers to the complete set of small (endogenous) molecules (with a mass <1500 Da) present within a given biological system,…

Promotor: A.P.IJzerman Co-promotor: A. Bender

During the course of drug discovery translational steps are made.

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

Cardiovascular diseases are still a major concern for the global health.

In this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer.

This thesis explored the molecular pharmacological mechanisms of targeting CB2R via investigation of novel drug discovery concepts such as target binding kinetics, allosteric modulation and biased signaling.

This thesis aims to test in vitro pipelines to rapidly and cost-effectively identify molecular mechanisms that drive adverse outcomes in clinical use.

Promotie

Een overzicht van awards en prijzen die in 2021 zijn toegekend aan onze medewerkers en studenten, maar ook bijzondere benoemingen aan de Universiteit Leiden en andere instellingen.

De faculteit biedt een internationale academische omgeving met 36% van de studenten, promovendi en onderzoekers uit het buitenland.

Kan het eiwit PRG4 helpen om de symptomen van reumatoïde artritis te voorkomen of te verlichten?

Cell-based medicinal products (CBMPs), such as CAR T cells, are highly complex biopharmaceutical products offering various treatment options for serious illnesses such as cancer or autoimmune diseases.

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

Promotor: Prof.dr. M. Danhof

Promotores: Prof.dr. E.A.L. Biessen, Prof.dr. T.J.C. van Berkel

Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

Cardiovascular disease is a major global burden and atherosclerosis is the main underlying pathological process.

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

Lipid formulations have demonstrated strong potential for nucleic acid delivery,particularly with the success of COVID-19 vaccines. Despite these advances, manyaspects of lipid formulations remain unclear.

The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

Adenosine is an endogenous ligand which exerts its action by activating adenosine receptors (ARs), while its circulating levels are controlled via a variety of mechanism and proteins, amongst others the equilibrative nucleoside transporters (ENTs).

In this thesis population pharmacokinetic and physiologically-based pharmacokinetic (PBPK) approaches were applied to investigate the influence of glomerular filtration (GF) and active tubular secretion (ATS) on renal clearance in children.

The progressive loss and degeneration of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). The onset and progression of PD can be triggered by multiple risk factors, for instance, genetic mutation, environmental exposure, and aging.

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Barrier function is the natural role of the skin. The lipid matrix present in the outermost layer of the skin, the stratum corneum is important for this function.

Promotor: Prof.dr. J.A. Bouwstra, Co-promotor: A. El Ghalbzouri

In this thesis, we aimed to better understand the underlying mechanisms involved in TNBC progression and metastasis formation and discover new targets to reduce breast cancer related deaths.