Can you tell us about yourself?

My name is Judith and I started working at Cergentis four and a half years ago. At the time, I had just moved back from the US where I had worked for three and a half years as a postdoc at Harvard Medical School and Massachusetts General Hospital, in Boston. But my husband and I wanted to come back at some point. So as soon as he had found a job in the Netherlands, we came back. Then, I had to start looking for a position and, in the end, found one here. It was exciting to be able to join Cergentis!

What piqued your interest in science?

In high school, I really liked all the science-related subjects. So, it was kind of an automatic choice to go to university and go for something beta-oriented. Actually, I didn’t expect that I would like biology that much. It was during one of those [university] Open Days where I got introduced, by two super enthusiastic students, to mitochondria. At that point, I thought: “well, you’re not going to study those tiny tiny things in the cells for years, right?” And now, I’m working on even smaller things! [laughs]

After my first master’s internship, in organic chemistry and pharmacology, I was convinced that I would not do a PhD. But during my second internship, at the department of genetics at University of Nijmegen, I had an amazing supervisor, who was really good at science but also really good at guiding people. That’s when I knew I wanted to do a PhD!

During my second internship, I was involved in the research group of Hannie Kremer that studied Usher syndrome. It’s a syndrome where people get both deaf and blind. It’s very severe and it’s actually a monogenic and a progressive disease. I got the chance to work with different technologies and to answer a lot of different questions thanks to my supervisor. He was a very good mentor!

What was your PhD research about?

I did my PhD in genetics at the department of dermatology. I studied psoriasis which is a multifactorial disease. For four years, I studied a group of genes known as LCE-3 which are expressed in the skin. I liked it a lot but also realized that even if I could do a lot of things with them, I was kind of done with the subject. I think some PhD students know they would like to study a certain topic forever, while others would rather start something new. I was in the second group.

How did your love for zebrafish come about?

I got the chance to write a grant proposal - which turned out to be granted - to work on something completely different. Namely, zebrafish. Again, studying genetic disease and ciliopathies but using zebrafish as a model system. That was also a great time because I had the chance to learn a lot of new things again! For instance, making my own model organism by genetically modifying those fishes. But also here, after a couple of years, it was just time for something new. Which is why I switched again and decided to come to a private company and work at Cergentis. Still in genetics but with a different angle.

We actually have a lot of customers based in Boston! Do you get the chance to travel back often?

Yes, I am very pleased that we have a lot of customers in Boston! With COVID, everything is of course a bit “shifted”. But prior to corona, I would go to Boston at least once a year to visit some of our customers and then stay a couple of days longer to see all of my friends that are still living there. And that’s such a nice benefit to be able to combine both. I really like Boston so it’s always nice to be back there!

A lot of things have changed for Cergentis since you first joined. Can you tell us a bit about its evolution?

Right after I joined Cergentis, in December of 2016, the company moved to a different building and grew a lot. When I started, we were twelve or so I think. At first, I was purely focusing on data analysis. And now I’m actually heading the Service team of nine people (including myself). The Service team includes everyone that is working with our customers’ samples (i.e., from the moment we receive them, we process them in the lab, we analyze the results until we share the TLA results and present them to our customers). So, for me personally, it means that I have also been growing professionally and that’s super nice! But we also have the R&D, the Bioinformatics, the Sales, Marketing & Business Development teams as well as all the supporting people from the Finance & Accounting department. So there has been quite some professional steps taken by the company since.

Can you tell us how we try to support our customers to the best of our abilities?

I remember a call we had with one of our customers. We were discussing the data and interpreting the results, but it was a bit unclear. And I had, let’s say, an idea of what the data was suggesting based on my experience and knowledge. So, I suggested some follow-up studies, to which they agreed. And good thing, it all panned out as expected. I think from that moment on, not only were they very convinced about the power of TLA but they also realized that the expertise that we have can also be very beneficial. Indeed, we have such a large database of knowledge at Cergentis, and our customers are definitely making use of it. For instance, they want to know if we see certain events more often or not and whether they are problematic. They also ask for advice and suggestions, as to what people usually do in such cases. Of course, we cannot provide any specific insights on the other projects we have done. But we do see general trends. I think that is quite valuable for our clients, because we are truly experts in genetic analyses and we analyze thousands of samples every year. That helps us understand what is going on in their own specific samples. Because most likely, we have already seen it. So we know when and/or how exceptional certain findings really are!

Given the burgeoning field of Cell & Gene Therapy (CGT), what would you say are some of the biggest challenges?

Of course, it depends a bit on what you are doing in this field and what kind of system you are using. With that said, we have seen quite a lot already. From what we notice, one of the major challenges is QC. That is very important of course. In the end the goal of CGT is that it should be used in patients. So you definitely want make sure that you have QCed, whatever you are doing, to the best of your ability. Ethically that’s also very important. But this can be very challenging, because those samples are usually super heterogeneous. You’re potentially looking at all kinds of different integration events depending on what kind of system you are using. But you still definitely want to know that the thing that you were aiming for, actually happened. So if it’s random integration, that it is actually really random. Or if it is targeted integration, that nothing off-target happened. So there, TLA is actually super nice because it can do both.

From what we have seen, cells that are used in cell therapy are usually treated either by a virally- or a non-virally based system. Usually for the virally-based system, we have learned from TLA data that we can not only study the integration sites, but can also say something about the integrity of the integrated sequences. For example, there could be deviations in the virus. That a subset of the virus can contain certain mutations. This is usually clear from our TLA data but not from the viral sequencing data, which then makes TLA super relevant to have as one of the QC steps.

However, we cannot sequence the virus itself. But we can sequence the producer cells as long as you have a stable transfection line. And we can look at patient samples. Sometimes, unfortunately for our customers, there are mutations identified in those viruses. But I think that it’s good to know that, because you don’t want to use such a virus in a clinical setting. So you definitely want to have those QCed right.

This was also recently recognized by the Genetic Engineering Biotechnology News, where I was interviewed specifically on this topic. From their research, it was clear that Cergentis has a very specified role and a very unique position to help QC those samples. And that is super nice, to get such appreciation from the experts in the field!

Can you tell our readers about any recent offerings in our services that they might not know about yet?

What I like at Cergentis is that we talk a lot with our customers. We do our service projects for them, help them understand what our TLA results mean, and we also advise them on the genetics. Our customers also trust and share a lot with us. One thing that we found out, is that they are interested in vector sequencing. Therefore, this is now something we currently offer as part of our add-on services. The same thing holds for the clonality assessment. We know – and I’ve been publishing this together with Novartis – that you can, based on the TLA results, find MCB-specific breakpoints (i.e., the breakpoint spanning the integration site from your genome to your vector-specific sequences). Indeed, if you’re not sure that your MCB is clonal and/or if you need some additional proof for it, then you can use (several of) those identified breakpoints to evaluate [MCB-derived] subclones and scan for the presence of the breakpoints. This will then give you an assurance of clonality, which has proven to be beneficial for some of our customers who are interested in such endeavors. Actually, this [clonality assessment] is also very much in line with regulatory requirements, for filing purposes. Since this is an important topic, we are also currently developing a special and extended reporting that will completely match the regulatory authorities’ expectations. This doesn’t mean that our standard reports cannot do the job but let’s say, that meeting regulatory expectations will then be truly complete. It will also be according to what your own QC department would expect from a report.

The Dutch are known to have the best work-life quality balance. As the Head of Services, you naturally have a great amount of responsibilities but what do you enjoy doing most in your free time?

Oh yes! I like to hike! If I have the time [laughs] Actually at Cergentis, it’s quite nice because a lot of us like to work hard but we also like to enjoy our free time. Of course, depending on your family circumstances, you might not work full-time. And there are a lot of people with young kids in this company so if your kid is sick or something, then people will understand, and it’ll be very easy to reschedule things. For me, that is quite important because I have two kids. But in terms of hobbies, I like to go hiking, I do boxing, I try to get my garden going [laughs] It’s looking much better than last year so let’s see if I can get some vegetables out of it! I like reading. I run every week so that should be on the list! And I like to play board games! Which I hope to do again with my friends once COVID is over.

This year, I also joined the party committee at Cergentis! I think it’s very nice that we have one. So every year we have another group of two people who takes care of it. Irina is doing it with me this year which is super nice! Now we hope that we will be able to do our yearly outing soon, which I think is the highlight of the year for everyone. But, in the meantime, we have done some online things which were also quite nice. An online murder game, which was a success. We’re now doing the European football cup pool game. I think it’s important to have such activities because the company is growing. As I said, there were about twelve people when I first started and now we’re with thirty-six or so! And especially with many people working from home, I think it’s very relevant that we stay in touch, that we get to know each other and that everybody feels welcome and has a good time when working at Cergentis. I think work-pleasure is as important as liking your job. It’s important that you feel at “home”, since you spend so much time working with your colleagues on a daily basis. And I think that Cergentis is supporting this well.