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Cock van Duijn

‘Bringing the patient to the chip’

Bio

Bio

Cock van Duijn graduated from the Agricultural University Wageningen in 1987 and gained a medical degree from the Erasmus University in 1992. She founded the MSc and PhD program in Genetic Epidemiology of Erasmus MC of which she is Scientific Director. She has been a member of the Royal Netherlands Academy of Arts and Sciences, since 2014.

POSITION AT:

Erasmus MC: Epidemology
Leiden University: LACDR

Different diseases, same genes

“When you study the human genome, it emerges that the majority of the most common disorders are the result of a large number of changes to the DNA that are in themselves harmless. These ultimately lead to common diseases, such as dementia and hypertension. The risk of a specific disease is determined by the sum of the number of genetic variants. However, no one had expected that there would be so many. In research into Alzheimer’s, we are already aware of around thirty genetic variants, but it will probably ultimately turn out to be hundreds. We are also finding that disorders are genetically correlated. For example, the genes that play a role in Alzheimer’s disease overlap with those for glaucoma, a disease in which the optic nerve deteriorates. The palette of glaucoma genes strongly overlaps with that of ALS. We are gaining an understanding of the genes that explain why diseases are clustered in a patient or family. The challenge is to translate this into the proteins and other molecules (metabolites) that relate to the expression of these genes and that can be used to develop drugs or serve as markers, indicating the start of the disease process.”

The lucky white ravens

“This is where the collaboration with Thomas Hankemeier from Leiden comes into its own. With his metabolomics facility, he can measure metabolites on a large scale across a broad range of concentrations. We are now measuring hundreds of substances in the blood of large groups of participants in epidemiological research. We are comparing people, who, based on their genetic profile, we know will go on to develop Alzheimer’s disease later in life. This allows us to identify the markers that predict the disease. They are the black ravens, or the unlucky ones. But we are perhaps even more interested in the white ravens: the group of people who are fortunate enough to have inherited a small number of variants related to the diseases from their parents. It is their metabolites that point the way towards the development of drugs.”

Brain on a chip

“These are the kind of moments when you think: this is too good to be true. For me, it happened at a meeting with Thomas Hankemeier and Rick Grobbee, from Utrecht, who is conducting research into cardiovascular diseases. Thomas was telling me about induced stem cells and his dream of converting them into cells that cover blood vessels. The idea is to create a ‘model organism on a chip’. This is how the idea of creating induced stem cells came about, converting them into brain cells and thereby creating a model of the brain on a chip. We now have various grants to translate the blood cells from ‘white ravens’ and ‘black ravens’ into a model of their brains on a chip. This will enable us to conduct large-scale research into what goes wrong in the brain of a black raven and what is so good about the metabolism in the brain of a white raven.”

Modelling complexity

“If you really want to tackle Alzheimer’s disease, you need to do it as early as possible, when the brain cells have not yet died off. We have secured various European grants and are now setting to work with the first prototypes, together with the industry. In particular, we are working on the interaction between the brain and the blood vessels. The ERGO study in Rotterdam suggests that this interaction is a key aspect in a large proportion of patients with Alzheimer’s disease in old age. There are still lots of improvements to be made. How effectively can you model the complexity of the brain and the blood-brain barrier? This is one of the first questions we intend to elaborate on in the Medical Delta.”