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Molecular Oncology

Divisions

Groups within research area Molecular Oncology

PietBorst.jpg

Piet Borst

Division
Molecular Oncology
Specialisation
Transporters, DNA base J

Introduction

With his senior post-doc Koen van de Wetering, Borst is trying to identify the natural substrates of a class of drug transporters, called Multidrug Resistance-associated Proteins (MRPS or ABCCs). A recent focus has been on MRP5 and MRP6. The main approach is to compare body fluids of WT and KO mice by LC/MS and verify by vesicular transport whether the compounds altered in the KO are transported by the missing MRP. The function of MRP5 (ABCC5) was long unknown, but we recently found that it transports neurotransmitter - like compounds and an entirely new class of compounds not known in mammals before. The absence of MRP6 (ABCC6) causes an inborn error, PXE, and identification of the natural substrate of MRP6 may allow substitution therapy of PXE. Up to 2013 Borst also worked on mechanisms of drug resistance in cancer cells and on biosynthesis and function of base J, a new base in the DNA of parasites discovered in the Borst lab.

The resistance project is continued by Sven Rottenberg in the NKI; the base J project is continued by Peter Myler (Seattle, US). Borst remains an adviser in both projects.

More about the Piet Borst group

JacquelineJacobs.jpg

Jacqueline Jacobs

Division
Molecular Oncology
Specialisation
Telomere Damage and Cancer

Introduction

Jacqueline Jacobs began her research group at the NKI in 2008, and investigates the mechanisms that preserve cell viability and protect against cancer development. Cells with unstable genomes are at high risk of becoming cancerous, and her group is particularly interested in the detection and repair of DNA lesions, which maintain genome integrity. These mechanisms are prevented from operating at natural chromosome ends by unique nucleoprotein structures, called telomeres.

However, telomeres shorten with every cell division, eventually compromising telomere protection and leading to cell death, senescence or genomic instability, which have important consequences for aging and the development of cancer.

More about the Jacqueline Jacobs group

DanielPeeper.jpg

Daniel Peeper

Division
Molecular Oncology
Specialisation
Functional Oncogenomics

Introduction

The Peeper laboratory develops and uses function-based genomic approaches to better understand the mechanistic principles of cancer progression, and to identify novel therapeutic targets for achieving more durable clinical responses for cancer patients. We have two main strategies: first, we wish to increase our understanding of how cancer cells originate and function, define their rewired signaling networks and subsequently expose their weaknesses. This will allow for the identification of specific and pharmacologically tractable vulnerabilities. Second, we wish to determine how we can manipulate various cell types from the patient's own immune system to enhance their cytotoxicity towards tumor cells. This approach should uncover new therapeutic targets on immune cells. By focusing on these two main research arms, our objective is to contribute to the development of combinatorial therapies, which simultaneously eliminate the patients' tumor cells and harness their immune cells.

More about the Daniel Peeper group

AlfredSchinkel.jpg

Alfred Schinkel

Division
Molecular Oncology
Specialisation
Improving Drug Efficacy

Introduction

We are interested in the proteins and organ systems responsible for susceptibility and resistance to anticancer drugs. Drug resistance is one of the major barriers to effective cancer treatment, and is often due to reduced uptake or increased efflux of the drug in tumor cells. Other problems include the toxicity of many anticancer drugs to normal tissues, and the variable tissue and tumor distribution found in each patient. Moreover, how drugs move around the body also determines in part how efficiently they can tackle the disease. Using knockout and transgenic mouse models, we aim to better understand the way the body handles drugs, thereby supporting the optimization of clinical chemotherapy.

Many of the proteins we study also have important physiological functions, often in the detoxification of endogenous potentially toxic compounds and metabolites. We therefore also have a strong interest in understanding these physiological functions, which can be studied readily in the knockout and transgenic mouse strains we generate. Basic insights into these physiological functions can also improve prediction of the consequences of chemotherapy approaches in which the activity of one or more of the detoxifying proteins is modulated to improve efficacy of drug therapy.

Thirdly, the proteins and systems we study are relevant in the handling of exogenous toxins and carcinogens by the body. We therefore also assess the in vivo impact of these systems on the susceptibility to dietary carcinogens and toxins. The activity of virtually all of the systems we analyze can vary dramatically, due to genetic polymorphisms or mutations, and gene induction or repression, or direct protein inhibition by dietary or pharmaceutical compounds (drug-drug interactions). Insight into their in vivo roles is therefore crucial in better understanding and potentially circumventing physiological, pharmacological and toxicological challenges to the body.

More about the Alfred Schinkel group

Emile Voest

Emile Voest

Division
Molecular Oncology
Specialisation

Introduction

My laboratory work is devoted to bringing personalized medicine to patients. It focuses on the impact of the host response on treatment outcome and the development of biomarkers that predict treatment efficacy. The results from such studies are subsequently translated in clinical studies. These translational approaches are performed across tumor types, with emphasis on epithelial tumors.

More about the Emile Voest group

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