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Biological Stress Response

Divisions

Groups within research area Biological Stress Response

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Alfred Schinkel

Division
Biological Stress Response
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

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