Kanaga Sabapathy

In the early 1990s, the first genetically modified mice were generated, and Kanaga was fascinated by the possibilities that this new method would open up. In particular, two NATURE-publications by Erwin Wagner, a Senior Scientist at the IMP, attracted his attention: the fos-knockout in 1992, and the jun-knockout in 1993. At about the same time, the first call for the IMP’s newly established International PhD Programme was advertised in NATURE – Kanaga thought this was calling and that something interesting was going on in Vienna.

He applied and joined Erwin Wagner’s group as a post-doc. “At that time, Singapore was totally unknown in the field of biology. And here is this this little, naive guy coming from Singapore. I was lucky to be accepted to the IMP.” When he became familiar with the lab, Kanaga was amazed at the diversity of topics covered. “Erwin gave his people complete freedom. He hired all these people and then let them do whatever they wanted, and they all turned out great papers. We always wondered how he did it. There were so many different projects going on: AP-1, c-Jun, c-Fos, EGFR, ADPRT... seemingly unrelated topics, but with a focus on cellular signalling and disease modelling.”

Kanaga spent most of his time working on JNKs, the c-Jun N-terminal kinases. Using the newest technologies, he knocked out JNK-1 and JNK-2, trying to understand their role in development and disease. He carried out some of the work in collaboration with Michael Karin from UCSD, a personal friend of Erwin Wagner. Meanwhile, in a side-project, Kanaga worked on p53, a transcription factor which is often mutated in cancers. Erwin had casually introduced him to the tumour suppressor gene, presenting him with some preliminary observations made in the lab by a short-term visiting scientist. “That opened up my eyes to p53, and eventually we published an EMBO paper on the role of p53 in embryonic stem cells.”

The wide spectrum of research topics that were undertaken in and across labs at the IMP made it an invigorating and intellectually stimulating environment to be in, and meeting colleagues from other labs over lunch added even more perspectives. Apart from the cafeteria, the best place for a casual exchange was that famous social-room/kitchenette, known to insiders as Joe’s Disco. He quipped, “I would go there every day, bringing my home-cooked food, and I would meet people from Hartmut Beug’s lab, Meinrad Busslinger’s lab, Kim Nasmyth’s lab - I knew pretty much everybody in the building. We would meet in the kitchen, eat our lunch and talk about our research. I remember vividly when Stephen Nutt left his pro-B cell cultures over Christmas, and he saw macrophages developing from the Pax5 knockout pro-B cells after his return, leading to the discovery of Pax5’s B-lineage commitment function. He wanted to talk to me about this because I had an immunology background... These are beautiful memories. Literally, it just felt like science was in the air, all the time.”

Looking back, Kanaga feels lucky to have come to Vienna. He adds, “IMP is one of the best places to do science”. What made it so special? “Obviously it's the people. Max Birnstiel (the founding director) hired amazing people as group leaders, and these amazing group leaders hired very good people in turn. It was a competitive and yet collegial environment, full of top-notch researchers. Even if they were junior when they came in, the environment that was created by all these very good people made everybody else become good as well. It was like a factory that moulded all these smart people.”

"What made the IMP different was the talent, and the resources that were provided to ensure that talent succeeds. Even in those days we had the sequencing service, the primer service, the imaging and the FACS facility…. at the IMP, they were always looking out for recent developments in technology to ensure that they are incorporated so that people can use them and succeed. I think two important ingredients for success are: talent and resources."

Meanwhile in Singapore, scientific research was still in its infancy. But in 1999, around the time when Kanaga’s term in Vienna was coming to an end, the National Cancer Centre Singapore opened and Kanaga became one of its first PIs. Rather than following up on his JNK-research, he felt he had to find a new focus. “I wanted to do something where I would be recognised for my own contributions, and since I was joining a centre with a focus on cancer, I decided to work on p53. It was a big and bold decision, and equally risky, as I had only published this one paper on p53 and the field was rather new to me, so it was a very big decision. However, on hindsight, that decision turned out well for me.”

With p53 being the most mutated gene in cancer, Kanaga set out to target p53 mutations in a way that could be of therapeutic benefit. Although his research was very focused on p53, he tried not to narrow down his view. That led him to the p73 gene, a homologue of p53 that is often overexpressed in cancers. Again, it was a totally new field. The gene had just been cloned recently and there were very few publications around. Kanaga and his lab have since investigated the key p53/p73 tumour-suppressor pathway in detail and focused on generating novel strategies to develop tumour- and mutation-specific therapeutic molecules. They now have two patented technologies to target mutant proteins – mutation-specific siRNAs and mutation-specific antibodies - and they hope to get them to the clinics soon.

In 2007, Kanaga became Professor at the Duke-NUS Graduate Medical School and since 2013, he has been the Research Director of the Academic Clinical Program in Oncology at Singhealth. Having held leading positions in research for many years, he is still drawing from one or two lessons picked up in Erwin Wagner’s group. “One is intellectual freedom. We were never told ‘don't do this’. Instead, it was ‘if you want to try it, go ahead.’ I really value the freedom to explore, since there are no boundaries in the exploration of science. Inspired by this work ethos, we are also trying many different things in my lab. For instance, even though we are a cancer-focused lab, we now have a novel story coming out on diabetes.”

And the second thing? “Erwin was an amazing collaborator, even in those days, before the internet. We used to go to his office around five o'clock in the evening, and he would call his collaborators in the US and have a chat. There was a famous phrase in our lab, ‘clone by phone.’ Sometimes, you didn’t need to clone a gene yourself. If someone had already done it, it was just a phone-call away.

We learned a lot about collaboration, because sometimes it’s just impossible to do everything yourself when you don't have the expertise. Knowing how to work together with people in different fields and sharing the fruits of the labour - that's something I learned at the IMP and which I dearly cherish.

To sum, my five years at the IMP and Vienna were one of the best years of my life and I am grateful for the experience and for the opportunities."

By Heidemarie Hurtl, published in 2022