ERC Starting Grant: Kai Kretzschmar's €1.77M award to study oral cancer

Approaching the 7-year post-PhD cut-off date for applications to the ERC Starting Grant, Dr. Kai Kretzschmar of the Mildred Scheel Early Career Centre for Cancer Research, a funding initiative of the German Cancer Aid at the University Hospital Würzburg, was awarded almost €1.77 million for his project, OralNiche. The project aims to dissect the impact of epithelial stem cell niches on oral cancer heterogeneity. We are proud to have supported Kai with a Review service towards his successful application to this prestigious program. Read our interview with Kai below as we learn more about the project and his experiences in applying to ERC StG with the support of Catalyze.

Demystifying the heterogenous landscape of oral cancer

While other cancers have seen great reductions in mortality over recent decades, survival in patients of oral squamous cell carcinoma (OSCC) – 90-95% of all oral cancers – has increased only very little over recent decades. This is not due to a lack of rigorous study, but because OSCC itself is a heterogeneous cancer type with varying and hard-to-predict treatment responses.

Moreover, OSCC arises from a tissue with a high degree of structural heterogeneity, the oral epithelium, which is maintained by site-specific proliferation and differentiation of oral epithelial stem cells (OESCs). Thus, it is possible that the differences between distinct OESC populations contribute in turn to the heterogenous nature of OSCC.

Kai highlights,“The big issue with this disease is it presents in a very heterogeneous fashion. And it’s difficult to determine if this is, for example, due to the heterogeneity of the tissue, or if is it something that is imprinted by the mutations present in the patient.”

Addressing 3 key objectives in the project

In the OralNiche project Kai will, for the first time, systematically and comprehensively characterise the OESC pools, dissect the key mechanisms that drive development of highly specific oral epithelial sites, and define their contribution to OSCC heterogeneity.

Kai underlines how his curiosity drove the creation of the project:

“Core to the project is understanding how the different oral sites all have their different functions and morphology. So how do these stem cells function? How do they orchestrate differentiation? In the end, the correct tissues are built and we want to understand how this is achieved.”

Kai continues, “We then want to understand if this affects oral cancer – some parts of the oral cavity are differently affected by primary or metastatic cancer than others. I am curious, from a biological perspective, what is actually allowing this to be?”

Applying to ERC Starting Grant                             

ERC Starting Grants are designed to support excellent Principal Investigators at the career stage in which they are starting their own independent research team or program. Applicant Principal Investigators must demonstrate the ground-breaking nature, ambition, and feasibility of their scientific proposal. Kai’s winning submission to the program came in his 7th year in research, post-PhD – the final year of eligibility for the ERC StG.

Kai says,“This was the first time I tried and the last chance I had, so I was really pleased to get it. This grant gives you the freedom to explore something a bit like a ‘blue sky’ idea – that is high risk, high gain.”

Continuing, he points out the value of having support from Catalyze:

“Catalyze was really helpful with, in particular, the formalization and structuring of the proposal, and in my case, keeping me to deadlines. Having their input also helped with finding a good balance between general and specific information. This was important, because the proposal also needed to be accessible to those who are not experts in this specific field.”

Aiming for improved patient survival in OSCC

In his project, Kai aims to make real impact for OSCC patients through two critical parts of the project that will focus on establishing early stage OSCC biomarkers to improve early diagnosis, and deploying 3D organoid cultures to model the malignant cells.

Kai explains, “I am interested in whether we can find biomarkers that allow us to determine, at an early stage, whether a tumour develops. Also, by using 3D organoids we will be able to immediately test our findings, for example by trying different treatment options.

“In the much longer term, ideally one could develop personalized precision medicine guidance. We are aiming to find biomarkers but also identify tools with which we can pre-select certain treatments for patients.”

Patients make the project possible

As Kai emphasizes, the OralNiche project and many others like it are only made possible by patients who allow their tissue to be used for research.

“This part of the project is really based on patients giving their samples for our research. I am very thankful to those that donate tissue for research, because patient tissue is essential for us to be able to validate anything that we see.”

Kai adds,“Without people giving tissue for research, many, many important research projects would not be possible – and this is one of them.”

Advice for other applicants to ERC Starting Grant

To finish, Kai shares his advice for other applicants to the ERC StG:

“Start early and define the ‘big picture’. You need to have an exciting, interesting question. You should develop a clear elevator pitch that you can explain to anyone – something Catalyze tried to get out of me – then build everything around this, and build experiments that fit this.

“Getting feedback from experts in your field is also important. I had a few friends and colleagues who gave me their grant applications, and I could look at those – they were all put together differently, which showed me there are many ways of writing the proposal. I also asked for really honest and thorough feedback on my proposal.”

Catalyze is proud to have supported Kai towards his successful application to the ERC Starting Grant.

Read more about Kai’s research