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Gautam Kok

What was your PhD about? 

"My PhD followed my research internship with Sabine Fuchs, where I have been working on developing new therapeutic strategies for metabolic diseases.

I started to work on a newly discovered disease caused by genetic defects in the IARS1 gene, encoding isoleucyl-tRNA synthetase deficiency. The research started following the death of a 4 month old child in the Wilhelmina Children’s Hospital, who turned out to have mutations in IARS1. IARS1 belongs to a group of enzymes, the ARS1 enzymes. These are responsible for an important step in protein synthesis: coupling the building blocks of proteins, amino acids, to a carrier, called transfer (t)RNA. Over the years, I have investigated the disease mechanism on a cellular level. I discovered that patient-derived fibroblasts were more sensitive to the ARS1 specific amino acid deprivation in terms of protein synthesis and cellular proliferation. I then tested amino acid supplementation in four children with various ARS1 deficiencies with spectacular effects. Next, I unraveled new physiological functions of the ARS1 enzymes.

At the same time our group is involved in genetic editing as a treatment strategy for metabolic diseases. In the perspective of liver organoid/stem cell transplantations, I have investigated the need to match for HLA by performing a large retrospective cohort study of all patients with liver transplantations in the Erasmus MC. Furthermore, I meta-analyzed the current literate that uses genetic HLA matching.

Towards the end of my PhD, in vivo genetic editing has become a more realistic option. Therefore, a friend and I thought of a plan to develop an in vivo treatment strategy for genetic epilepsy syndromes. We got good first results of editing POLG-deficient fibroblasts from a patient with Alpers Huttenlocher Syndrome. This is a severe pediatric genetic disease of the brain, liver and muscles, with sudden onset that often leads to death. We are currently acquiring funding to continue this line of research after defending my PhD. 

All three parts were based on clinical cases from our own hospital. I wish to continue to perform translational research as part of my clinical career."

What is your fondest memory of your time at RMU?  

"I have always admired the mix of people working there – different cultural and educational backgrounds, different levels (from students to professors) and different fields. This makes it very easy to approach people, and helps start scientific collaborations. Above that, the atmosphere is great and I’ve made good friends. And we’ve had some great parties with the PhD programme ;)"  

What are you going to do next?  

"Having studied SUMMA, I look forward to a combined clinical and scientific career. In the coming year, I am going to figure out if would like to continue in pediatrics or (pediatric) surgery. I am currently working as a junior doctor in the department of surgery in the Sint Antonius Hospital (in Utrecht and Nieuwegein)."