Our PhD students are trained to become experts in the multidisciplinary field of personalised therapeutics.
Jonas den Heijer
Genetic screening in Parkinson’s Disease in order to identify patients who can participate in clinical trials with new targeted therapie
Institute: Centre for Human Drug Research, Leiden University
Start date: April 4, 2017
Supervisors: Dr. G.J. Groeneveld, Prof. dr. A. Cohen
The most common genetic risk factor currently known to develop Parkinson’s disease is a mutation in the GBA1 gene, which occurs in 5-10% of patients. A new drug is being developed that targets the enzyme glucocerebrosidase, encoded by GBA1 and which is expected to only benefit patients with such a mutation. The Centre for Human Drug Research is performing the early phase clinical studies with this drug and in parallel is genetically screening over 3000 patients with Parkinson’s Disease in order to identify sufficient patients with a GBA1 mutation.
Institute: Leiden University Medical Center; Department of Clinical Pharmacy & Toxicology (collaboration with Dept. of Medical Statistics)
Start date: March 1, 2017
Supervisors: Prof. dr. H.J. Guchelaar, Dr. K.J.M. Schimmel, Dr. A.G.T. Terwisscha van Scheltinga and Dr. S. Böhringer
Drug repositioning, i.e. finding new applications for existing drugs, has taken on a new dimension with the availability of vast amounts of publicly available data and computational methods. One such method is gene expression signature reversal, which is based on the observation that drugs which affect gene expression in the opposite direction of the way genes are perturbed in diseased states, often turn out to be therapeutically indicated for that disease. Since there exists a lot heterogeneity within the same tumor type, I will be investigating whether using individual tumor gene expression profiles provides additional benefit to reposition drugs for cancer.
Marieke van Herk
The tumour microenvironment and development of immunotherapies in colorectal cancer
Institute: Leiden University Medical Center, Dept. of Pathology
Start date: November 1, 2016
Supervisors: Prof. dr. J. Morreau; Dr. N.F. de Miranda
Colorectal cancer is one of most diagnosed tumours in the western world and to date patients are often treated with general options as radiotherapy, chemotherapy or surgery . However, the tumour microenvironment differs highly between tumours, which highlights the need for personalised therapies. My work focusses on the identification of immune-phenotypes in the tumour microenvironment of colorectal cancers. Later on, these findings can be utilised to develop tailored immunotherapies specific for patients with those phenotypes.
Development of a universal delivery system for personalized cancer vaccines.
Institute: Leiden University Medical Center, Dept. Immunohematology and Blood transfusion
Start date: October 1, 2016
Supervisors: Prof. dr. F.A. Ossendorp (LUMC); Prof. Dr. W. Jiskoot (LACDR).
In a joint program of the LUMC and LACDR we have recently shown the potential of liposome-based cancer vaccines. The cancer vaccine consist of tumor-specific synthetic peptides which are encapsulated in cationic liposomes. The vaccine aims to activate tumor specific T-cells resulting in tumor regressions. Our next aim is to further develop the liposome platform for patient-specific peptide vaccines based on identified DNA mutations in the patient’s cancer cells, the so-called neo-epitopes, and production of the personalized vaccine in the LUMC’s GMP-facility. The project is funded by Leiden University Translational Drug Discovery & Development Molecule to Man award.
Maaike van der Lee
The use of rare variants in pharmacogenomics
Institute: LUMC - Dept. of Clinical Pharmacology & Toxicology and Dept. of Clinical Genetics
Start date: October 16, 2016
Supervisors: Prof. dr. H.J. Guchelaar, Dr. J.J. Swen, Dr. M. Kriek
With the current golden standard of genotyping the focus lies on common variants (occur in > 1% of the population). However, it is known that rare variants (<1% occurrence) are often seen and can contribute to the phenotype as well. To identify these rare variants new methods and analyses need to be developed. I will work on establishing a method to identify rare variants and assess their contribution to the phenotype. The focus will be on the liver enzyme CYP2D6, which metabolises 25% of all prescription drugs. My project is funded by the EU H2020 project U-PGx (No 668353).
Cancer-induced somatic mutations in G protein-coupled receptors: The case of the adenosine receptors.
Institute: Leiden Academic Centre for Drug Research, Dept. of Medicinal Chemistry
Start date: September 1, 2016
Supervisors: Prof. dr. A.P. IJzerman; Dr. G.J.P. van Westen; Dr. L.H. Heitman
Cancer associated viral GPCRs that are constitutively active can lead to abnormal cell growth. Moreover mutated GPCRs have been found in an estimated 20% of all cancers. All four subtypes of the adenosine receptors are possible targets for the development of novel approaches to the treatment of cancer both from a theoretical point of view and based on literature evidence gathered from patients (presence of mutations and survival). Here we propose to investigate and exploit these proteins as targets in cancer based on our previous work exploring the presence of mutations (Van Westen, Unpublished data, 2016).
Cathelijne van der Wouden
Making actionable pharmacogenomic data and effective treatment optimization accessible to every European citizen
Institute: Leiden University Medical Centre, Dept. of Clinical Pharmacy and Toxicology
Start date: April 1, 2016
Supervisors: Prof. dr. H.J. Guchelaar; Dr. J.J. Swen
Despite scientific and clinical advances in the field of pharmacogenomics (PGx), application into routine care remains limited. The Ubiquitous Pharmacogenomics Consortium’s (U-PGx) PREPARE Study aims to implement PGx testing of a panel of pharmacogenes, to guide drug and dose selection, and to determine its impact on patient outcomes and cost-effectiveness. PREPARE (PREeptive Pharmacogenomic testing for prevention of Adverse drug REactions) is a prospective, block-randomized, controlled, clinical study across healthcare institutions in seven European countries (n=8,100). My project is funded by the EU H2020 project U-PGx (No 668353).
The next step to CADASIL therapy, from CRISPR/Cas9 to biomarker development
Institute: Leiden University Medical Center; Department of Clinical Genetics & Department of Human Genetics
Start date: November 1, 2015
Supervisors: Dr. Julie W. Rutten, Dr. Saskia A.J. Lesnik Oberstein, Prof. Dr. A. Aartsma-Rus
CADASIL is a hereditary stroke and dementia syndrome caused by mutations in the NOTCH3 gene. Patients suffer from mid-adult onset strokes, migraine and dementia. To date, no treatment is available for CADASIL. In my project, we aim to develop genetic treatment strategies for CADASIL (e.g. NOTCH3 exon skipping), tailored to the sub-set of the most frequent CADASIL causing mutations. In addition, we aim to develop clinical biomarkers which can be used in possible future clinical trials to monitor disease progression. My project is funded by the Dutch Brain Foundation.