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April 2017 − Research Careers

 

The Spanish cancer researcher Óscar Fernández-Capetillo is in the business of tracking damage in the human DNA. His work is propelled forward by an insatiable drive for understanding. And once he did understand, he really turned up the stress, “replication stress”. An overdose of this, the biochemist found out, drives cancer cells to suicide.

 

Óscar Fernández-Capetillo almost became a stock market analyst. Computer Science was also an option, at a time when he was almost ready to leave science. Good thing, though, that men occasionally listen to their wives, as otherwise the 42 year old biochemist would not have gone on to become Spain’s leading cancer researcher. “My wife rescued me for the case, and I owe her what I am today”, the scientist says with a smile. In fact, he is the man of the hour when specialists around the world gather to discuss the influence of endogenous factors on the formation of cancer and the ageing process.

The focus of Capetillo’s scientific curiosity is a microscopic nucleus. Deep inside the human cell, it is the genome within, that not only dictates height, appearance, athletic prowess and artistic talents, but it also determines what makes us human. It plays its part in deciding whether a person is ailing or healthy, and whether they will die young or live to a ripe old age.

 

Insatiable curiosity

As far as Óscar Fernández-Capetillo is concerned, it is safe to assume that his genes may have equipped him with a predisposition: even as a child in northern Spain, he dissected prawns on the Atlantic coast, only to put them back together again like so many pieces of a puzzle. It was good practice! “I always wanted to be some sort of explorer“, says the Spaniard and adds, laughing, “I have an insatiable curiosity to understand things!”

It is therefore not surprising that Capetillo’s path led directly into research. After earning his doctorate in biochemistry at the University of the Basque Country in the Spanish city of Leioa, he completed a three year postdoc with André Nussenzweig at the National Cancer Institute in Bethesda, Maryland (USA). This is where he discovered his great passion for genetics research and DNA damage. “I was fascinated by understanding the key role that DNA damage plays in why we age or why we suffer cancer.”

Back in Spain, and still interested in DNA damage, Capetillo deepened his knowledge at the National Cancer Research Center (CNIO) in Madrid. As director of the “Genomic Instability Group”, he was looking for a new challenge, a niche in cancer research. He found it when he accidentally came across a journal article which hinted at the possibility of a connection between replicative stress and the development of cancer. Replicative stress? Capetillo’s curiosity was ignited. He was “burning” for the subject which, he found, had been ignored by the scientific community far too long. “Even though it is clear that DNA damage drives cancer and ageing, the sources of endogenous DNA damage in mammals are not as well understood”, regrets the biochemist.

Indeed, up to that point the focus of most cancer research had been directed towards exogenous factors, such as, for example, how toxic substances from the environment or UV and ionizing radiation lead our cells to mutate, thus triggering a variety of cancers.

Replicative stress, Capetillo's area of research, originates during cell division and is capable of damaging DNA. “We have discovered that a type of DNA damage accelerates ageing in mammals”. This is where the research comes in to develop new strategies against cancer. The basic premise: if stress during cell division will activate ageing, why not harness its destructive power and drive the mutated cells to an early death? Capetillo explains: “Regarding cancer, we have explored the idea of creating an ‘overdose’ of replication stress in cancer cells as a means to kill them.”

 

The drive comes from the heart

First successes verify the conclusions of the team, which has already moved beyond the basic research phase. “We have moved to the development of actual drugs that have already shown antitumoral efficacy in preclinical models”. The Spaniard is happy: a German pharmaceutical company has already licensed the therapy to bring the new agent to market. Capetillo is thus one big step closer to his goal of making a significant contribution to the fight against cancer. “In any case, it would feel great if I have contributed significantly to improve the treatment of some incurable desease”, he describes his researcher’s dream.

Capetillo is a cool analyst when he is in the laboratory, but the drive behind his achievements comes from the heart. This becomes evident when he talks about his Uncle Carlos who died young and who was his great inspiration. While he had completed his studies of Mathematics and graduated first in his class, he could not imagine spending his life with columns of numbers. So he pursued an additional degree in Psychology and went on to work with underprivileged children. A clear message for Capetillo: “One has to do what is right.”

And Capetillo must discover things. For him, that is the most important aspect of his profession. Despite fame and numerous awards, such as, for example, the Eppendorf Award, the EMBO Young Investigator Award, the ERC Starting Grant and many more, the scientist has remained modest.

 

An optimistic soul

Capetillo is a team player. He loves the scientific discussions with colleagues who drive him to new heights with constructive criticism and new ideas: “Creative, impulsive people, that is who moves the world!” Above all, Capetillo likes tolerant, generous people with a good sense of humor. “And humble and accessible people”, he adds. Asked about his greatest scientific successes, he answers modestly: “I do not see this business as a competition. There are several things that we have contributed that I find really exciting, for example, the discovery that embryonic stress can exert its influence later in adulthood, or the development of a new type of antitumor chemotherapy.” Even on the topic of failure he remains calm: “Just do many things. Hence, if one fails, well, you just move on to another!” He is not easily derailed – he is an “optimistic soul”.

 

Full of curiosity

That is true. In every respect: The father of four is happy to watch his children grow up, and when he is able to spend two weeks of vacation “at one stretch” with his wife and children. Despite the intensive research, Capetillo takes the time for a variety of hobbies: “To name a few: reading, fishing, mushroom picking, poker, stargazing – and a lot more. In addition, I am a very social person. I particularly enjoy being with my funniest friends!”

What does the future hold? It will definitely be filled with curiosity and scientific drive and the sensation of being just a little lost. Lost? Capetillo laughs: “Yes! If you feel a bit lost, and feel like you do not understand many things about your work, this means you are in the right place!”

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