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.

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 light of climate change, it is crucial to determine whether plant species can adapt to future climates to avoid extinction. Plants adapt to various conditions by altering their functional traits, such as leaf size or photosynthetic rate. Some traits appear linked and vary together between species,…

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

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

G protein-coupled receptors (GPCRs), one of the largest families of membrane proteins, are responsive to a diverse set of physiological endogenous ligands including hormones and neurotransmitters.

Het onderzoek binnen dit domein combineert conceptuele en praktische perspectieven op het gebied van het leren en doceren van tweede talen.

The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.

Promotor: J.A. Bouwstra Co-promotor: A. El Ghalbzouri

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.

Promotor: T. Hankemeier, Co-Promotores: T. Reijmers, L. Coulier

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

Europese burgers worden geconfronteerd met uitdagingen op het gebied van globalisering, migratie, technologische ontwikkelingen en klimaatverandering. Deze uitdagingen vergen het uiterste van onderlinge internationale en intergenerationele solidariteit, wat rechtstreeks betrekking heeft op de grondslagen…

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the pa…

Promotor: Prof.dr. J. Kuiper

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.

Cardiovascular disease is the leading cause of death worldwide.

Promotor: Prof.dr. M. Danhof

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.

Promotores: B. van de Water; P. Hogendoorn; J. Bovée Co-Promotor: E.H.J. Danen

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

Cancer is considered the silent pandemic of the 21st century and the second leading cause of death worldwide.

This thesis explores different avenues to develop insurmountable antagonists for CC Chemokine Receptors, such as CCR1, CCR2 and CCR5.

Cardiovascular syndromes are the major cause of death in Western societies.

Viral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge…

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

This thesis tackles the difficulty of predicting the liver’s clinical response to novel therapies, a challenge arising from interspecies differences and limitations of existing in vitro models.

Promotor: J. Kuiper

Promotor: J. A. Bouwstra

Promotor: Prof.dr. T. Hankemeier

Dit project ontwikkelt een wetenschappelijke methode om klinisch relevante nieuwe informatie te extraheren uit patiëntenforum-websites die ervaringen van patiënten bespreken over bv. medicatie, voeding, co-morbiditeiten, genetische factoren enz.

Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.

Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

Promotor: G.F.A. Kersten, W. Jiskoot, Co-promotor: B. Metz

De Faculteit der Wiskunde en Natuurwetenschappen is gevestigd op verschillende locaties in het Bio Science Park Leiden.

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

Drug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power.

This thesis investigates a pharmacological challenge model induced by Toll-like receptor 7 (TLR7) activation, focusing on skin inflammation and its implications for early drug development.

Inflammatory skin diseases such as psoriasis and atopic dermatitis can severely impact both the physical and social aspect of a patient’s life. Aberrant inflammatory responses are thought to be a major causative factor in these disorders, but an abundance of different factors contribute to the development…

The investigation into the bidirectional communication between the gut and its host is a rapidly growing area of research, attracting considerable attention for its potential to provide crucial insights into health and disease.

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.

This thesis focuses on enhancing predictions of central nervous system drug exposure using the LeiCNS-PK3.0, a physiologically based pharmacokinetic model.

According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).

This thesis investigated miniaturized mass spectrometry (MS)-based analytical methods to address challenges in analyzing biomass-restricted biological samples.

Nieuw handboek geschiedfilosofie van Herman Paul in de reeks 'Wetenschapsfilosofie in context'.

M. Danhof, Co-promotores: J. Freijer, A. Yassen