At the webinar of 27 May, the chair of the Medicinal Chemistry & Chemical Biology section announced the winner of the MCCB PhD Thesis Award: Dr Natalia Ortiz-Zacarias. The jury found her research to be original, multidisciplinary and ground-breaking.

Natalia Ortiz-Zacarias

Natalia Ortiz-Zacarias (right)

Were you surprised to win the prize?

‘Yes! I must admit that I was very surprised, since I didn’t even know I was nominated. So when I heard that I won, I was very happy to hear it.’

What was so special or interesting about your thesis that you received a prize for it?

‘During my PhD, we studied novel concepts to target chemokine receptors (CCRs), you could call that the main topic of my thesis. The main concept was insurmountable antagonism. It’s quite a mouthful! But basically we wanted to create antagonists that could inhibit CCRs, even though there’s a high concentration of active chemokines. The antagonists could then counteract the effects of chemokines during a disease.

To reach insurmountable antagonism, we developed intracellular antagonists, which are unique in the GPCR-field. These intracellular antagonists should not interact with the chemokines because of their intracellular binding site. Also, we discovered that some of our compounds inhibit both CCR2 and CCR1, or CCR2 and CCR5, and thus were multitarget antagonists. In a lot of diseases, multiple receptors are active, so if we can inhibit those with a single antagonist, that would be very relevant.

The collaborations we had are also pretty important to me. With the group of Prof. Tracy Handel from the University of California San Diego we managed to solve the crystal structure of CCR2 and thus confirmed the intracellular binding site we were targeting. In another collaboration ­­– within the Leiden Academic Centre for Drug Research – we found that one CCR2 antagonist, an orthosteric compound, also inhibits atherosclerosis in mice.

Finally, I want to thank my promotors, Prof. Ad IJzerman and Prof. Laura Heitman. They were really instrumental for my work and life as a PhD student.’

What will you do with the prize money?

‘I hadn’t really thought about it yet, since I still need to receive the prize. But I really like paintings, so maybe I’ll buy one for home, or maybe a small one for my office.’

What are your future plans?

‘Right now, I’m doing a postdoc at the LACDR in the group of professor Heitman and at the ONCODE institute, where I focus on GPCRs in cancer. I am still working on chemokine receptors, but now with an oncology perspective. That’s ultimately my plan, to steer my career towards oncology focused or disease-focused research.’

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