Dr. Henrik Daub
An interview with Dr. Henrik Daub
Dr Henrik Daub serves as Senior Vice President Science & Technology at Evotec in Munich, Germany, where he oversees the development and application of proteomics technologies in drug and biomarker research.He received his PhD from the Max Planck Institute for Biochemistry in Martinsried, for the discovery of fundamental signal transduction mechanisms. As a group leader at the Max Planck Institute for Biochemistry, his research focused towards chemical proteomics and quantitative phosphoproteomics.Dr Daub was a founder of Kinaxo, a biotech company specializing in high-end proteomics services, later acquired by Evotec.
Can you tell us a bit about your research?
We’ve been carrying out protein biomarker research for a number of years. Starting with cell culture models, and xenograft tissue from mouse cancer models, we searched for proteins, combinations of proteins and phospho-sites that correlated with response to drug treatment or resistance to drug treatment.
In this way, we’ve managed to achieve preclinical validation of found protein biomarker candidates. But, still, a major hurdle is the translation into clinical context, combined with issues such as protein and protein modification stability. I think these are areas where heat stabilization technology could make a difference.
What are some of the challenges you face in your biomarker research?
In our current research we actually work with FFPE tissue samples in some studies. This works reasonable well, but obviously not for analyses of post translational modifications, due to their dynamic nature.
Our key challenge when working with tissue samples is to make sure the whole process is as standardized as possible. You need to control for ischemia times and you need more replicates compared to working with cell cultures.
Also, discovery type proteomics while being an extremely powerful approach to identify new protein biomarker candidates, is not the ideal approach to follow up on them. Instead, we use a different type of assay – targeted mass spectrometry – for confirmation and verification of initial candidates. This allows precise, robust quantification with higher throughput, and even hundreds of samples can be tested in one project.
With regard to the future, it’s still open whether or to which extent mass spectrometry can be used as routine technology in clinical practice, or whether it’s more straightforward to use established formats like ELISA and IHC.
There is a downside to using immunoassays for candidates from unbiased discovery efforts, as you might end up with proteins for which no suitable antibodies are available. Developing new antibody reagents can take quite some time and also come with significant costs. Here, targeted mass spectrometry can serve as a good bridge as such assays can be established within a couple of weeks.
How important is sampling?
Sample quality and sample preservation are essential. We can only work with the data we are able to acquire from the samples provided to us.
When we perform tissue proteomics, or phosphoproteomics, there is more variation compared to cell culture based experiments. You can compensate for this by increasing the number of samples, but it would be preferable to reduce variation by improving the sample preparation steps.
Does the scientific community focus enough on sample preparation?
There is certainly some awareness about the importance of sample prep, although there is often a question mark as to how well it is addressed. It’s part of the discussion, even though there is generally more focus on mass spectrometry analysis and the results that are obtained.