Chordoma Foundation

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Physician-scientist choses career path in chordoma research

Youssef_YakkiouiYoussef Yakkioui is fascinated by neurosurgery, and by the biology of tumors. The Dutch medical doctor and PhD candidate is planning a career as a physician-scientist – but he is already contributing to our understanding of the molecular underpinnings of chordoma and helping to lay the groundwork to develop new therapeutic approaches.

Yakkioui first learned about chordoma while studying medicine and biomedical research at the University of Maastricht in his native Netherlands. “I asked the chief of neurosurgery if I could shadow him for a day in his clinic and in the operating room. As it happened, one of the patients we saw that day had a chordoma and the chief’s main interest in neurosurgery was operating on skull base chordomas. One of the main problems we face, the chief told me, is that we understand too little about the clinical behavior of these patients after their treatment.”

Intrigued, Yakkioui started researching chordoma and his curiosity quickly grew. “I was fascinated by the idea that the embryonic notochord just goes haywire and starts to make tumor cells, and I was surprised how little research had been done at that point. The more I read, the more fundamental and clinical scientific questions came to me. I decided to try to find answers.”

In March 2013, as his interest in chordoma was growing, Yakkioui attended the Chordoma Foundation’s Fourth International Chordoma Research Workshop in Boston. “It was incredibly valuable to connect with other scientists from across the world and exchange information and ideas. It made me even more enthusiastic about chordoma research and raised a lot of new questions for me.”

One of the questions Yakkioui would like to answer is: What proteins are involved in the development of chordoma tumors?

“A lot of chordoma research to date has focused on the genetics: Which genes drive notochordal cells to become cancerous; which genes are turned on or off,” explains Yakkioui. “That has yielded some very important results, including the discovery of the brachyury gene’s involvement in chordoma development. But little is known yet about how those genetic changes affect the pattern of protein expression in chordoma cells.”

Most genes are blueprints for proteins that are produced by the cell; it is the protein that is largely able to affect the cell’s behavior, and that can be targeted by drugs. “Understanding which proteins are switched on or off in chordoma will hopefully give us new targets for therapies,” says Yakkioui.

To answer this question, Yakkioui is guided by Professor Dr. Yasin Temel at the University of Maastricht, as well as collaborating investigators at the University Bordeaux in France. In 2014, the Chordoma Foundation awarded a grant to enable the international team to compare cells from chordoma tumors with healthy notochord cells to see which proteins are altered in chordoma and which might be involved in the malignant transformation of healthy cells into chordoma.

Their results show clear differences in protein expression between chordoma and notochord, pointing the team to several potential therapeutic targets. Yakkioui and colleagues are now preparing a manuscript describing their findings, and, this summer, Yakkioui will be back at the 2016 International Chordoma Research Workshop to share his data with the worldwide research community.

Ultimately, Yakkioui intends to pursue a career that combines research with the surgical treatment of patients with skull base chordoma. In the mean time, as he finishes his PhD program, he is always trying, as he put it, “to get all of the questions in my head answered.”