Another research line is the development of a spatial CNS drug distribution model, by ultimately including the 3-dimensional anatomical organization of the CNS.

Although rarely considered by the pharmaceutical industry or clinicians, 24-hour rhythms in physiology are a factor of potential influence on the pharmacokinetics and pharmacodynamics of drugs.

How can we extend the drug residence time to combat diseases more effectively?

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

This thesis investigates how non-genetic factors, such as inflammation and concomitant medication, impact hepatic drug metabolism and subsequent drug metabolizing phenotype predictions.

During the course of drug discovery translational steps are made.

Can effective synergists be identified to enhance the effect of antibiotics against Gram negative pathogens?

Heart failure is a major health care problem with high mortality.

Source: ChemMedChem (2015)

Promotor: A. Kros

Promotor: Prof.dr. J. Kuiper, Co-Promotor: S.C.A. de Jager

Data analysis with Python and R are rapidly becoming essential skills for modern scientists. Therefore, we are offering courses to develop your scientific computing skills. Those courses are optional for LACDR PhD candidates.

Human and animal cells are very complex: very different chemical processes are going on at the same time, but they are separated from each other because the cells are divided in compartments. These compartments may also have a profound effect on the potential efficacy of therapeutics, because the drug…

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

Acute cardiovascular syndromes, including myocardial infarction or stroke, are the principal cause of death in the Western society. The main underlying pathology of cardiovascular diseases is atherosclerosis, which is caused by the accumulation of lipids and inflammatory cells in the vessel wall, in…

Promotores: Prof.dr. H. S. Overkleeft, Prof.dr. G. A. van der Marel

Activity-based protein profiling (ABPP, also termed chemical proteomics), is one of the pillars of chemical biology, and at LED3 we have taken it to the next level. ABPP allows the assessment of protein function in live cells and tissues, which means that the activity of a complete protein family can…

In this article, Marieke Liem and Kim Moeller revisit Goldstein’s framework on the drugs-violence nexus

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

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

This project’s aim is to critically assess current homicide data sources in order to develop a proposal for long-term EU-level monitoring of DRH.

Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.

Exploring the mechanism of targeted nanoparticle-mediated drug delivery using the zebrafish model

The lack of success of new CNS drugs in clinical development is in part due to the complexity of the CNS, unexpected side effects, difficulties for drugs to penetrate the brain, but also by the lack of biomarkers.

The aim of this thesis is to expedite and ensure the systematic accuracy of clearance scaling from adults to paediatric patients, with a special focus on drugs undergoing hepatic metabolism.

Promotor: Prof.dr. A.P. IJzerman, Co-Promotor: Dr. L.H. Heitman

Analysis of drug adversity

Establishing human induced pluripotent stem cell (iPSC) CRISPR-Cas9-based fluorescent reporter cell lines for NF-kB signalling. We will use this to enable studying the dynamic activation and downstream signalling of Toll-like receptor and cytokine signalling in iPSC-derived differentiated cells in a…

Source: Nature Biotechnology, Volume 2014, Issue June (2014)

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

The path to rational drug and dose selection

From descriptive to physiological models that can predict oral absorption and elimination of CYP3A substrates across the pediatric age range.

He’s a fast and animated speaker, which is only logical because Gerard van Westen is driving an express train. His destination? A virtual human, consisting of algorithms that predict what an administered substance will do in the body. The train is already a long way down the line and the pharmaceutical…

Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst

High throughput microscopy

PhD defence

Promotor: B. van de Water

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

The kidneys play a major role in the elimination of drugs. In children, the exact age-related physiological changes underlying kidney function remain largely unknown.

Drug induced organ toxicity is the main problem of the drug development and drug usage in the clinic. The liver and kidneys are the most sensitive organs towards drug induced toxicity.

The polypept(o)ide hybrid material attracted more and more attention over the past decade by combining the multifunctional characteristics of polypeptides with the shielding characteristics of polypeptoid-pSar possessing similar properties as a shielding material as polvethylene glycol(PEG). Polysarcosine…

Can a new proteomics workflow be developed to link genes and gene clusters to bioactive molecules, identify novel compounds and enhance the production in the Streptomyces lividans enzyme?

Supervisor: Lizi Xia

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

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.

Source: Biosens Bioelectron, Volume 74, pp. 233-42 (2015)

Can zebrafish larvae be used as a behavioural model for screening natural products as potential neurotropic drugs?

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

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…

Source: J Cheminform, Volume 7, Issue 1 (2015)