Musings from The Power List: Michal Holčapek

What are your main research aims?
 

Lipidomic analysis of biological samples using a combination of advanced mass spectrometric and chromatographic techniques with applications in the discovery and translation of cancer biomarkers for clinical screening.

Which analytical frontier in human health and disease are you most excited about?
 

My answer is related to our own research. In our spinoff company, Lipidica, we are working on the clinical translation of a patented methodology for the early detection of pancreatic cancer based on lipidomic analysis of human blood. We use UHPSFC/MS for high-throughput quantitation of about 150 lipid species, and then multidimensional statistical analysis can differentiate patients with pancreatic cancer or other types of cancer from healthy volunteers with accuracy over 90 percent. Next is to begin clinical validation, and then we plan to use this method for early cancer detection for high-risk people. My dream is to launch a national pancreatic cancer screening in the Czech Republic and then expand to other countries. We are able to detect early stage cancer and precancerous states, which could be a real game changer in the early detection of pancreatic cancer as one of the most lethal diseases, caused mainly by the absence of any screening program. 

How would you spend a $1 billion research grant?
 

I would spend it on the establishment of a multiomics laboratory, which will be equipped with cutting-edge instrumentation for individual omics layers, such as lipidomics, metabolomics, glycomics, proteomics, and transcriptomics. Of course, a strong emphasis must be placed on the bioinformatic part of such multiomics integration so that the research group can investigate the biological mechanisms of observed dysregulation in human diseases. Mostly, research groups are doing observational research, which means that they observe some dysregulations of metabolites or proteins for some diseases, but they do not understand the reasons behind such dysregulations. This research is worthy of potential clinical translation, but it still lacks the biological mechanism. If we can integrate multiomics data together with suitable animal or cell line models with the final verification on human data, then we may pave the way towards the development of new drugs targeting dysregulated metabolic pathways. Many researchers dream of this direction, but the complexity of such multidisciplinary integration and the high costs seriously limit the range of laboratories that can afford it. The research groups should have two major goals: 1/ investigate the biological mechanisms of observed dysregulations in selected human diseases, and 2/ translate methodologies for screening and progress monitoring into real clinical practice.

How will analytical science transform how we diagnose and treat over the next 20 years?
 

I hope for improvements in high-throughput quantification of many biomolecules (lipids, metabolites, proteins, etc.), which will be correlated with the prediction and diagnosis of serious human diseases. The highest possible quality of analytical measurements and subsequent statistical evaluation of the data are prerequisites for such transformation because the mediocre quality of analytical data does not lead to the goal. I believe that physiological ranges of concentrations will be defined for particular subgroups (gender, age, BMI, ethnicity, etc.), so the outlying values will be used for the prediction, diagnosis, and treatment monitoring of many diseases using advanced statistical algorithms in combination with machine learning approaches and AI. However, the basis will always be the quality of the analytical measurements.

What is the most exciting development or emerging trend in analytical science today?
 

In the field of mass spectrometry and its coupling with chromatography, the speed of innovation is very fast because there is a great competition due to the number of leading manufacturers which come with technical innovations annually. A lot of interest has been paid to ion mobility technology, where the resolution provided by leading vendors increased quite significantly, but I still see some limitations in terms of the combination of sensitivity, ion mobility resolution, and the possibility to analyze a broad range of analytes. The cutting-edge configurations of high-resolution tandem mass analyzers offer the ultimate analytical power, which would have been a dream one decade ago. In liquid chromatography, I really appreciate the trend of bioinert systems with surfaces, which significantly reduce the unwanted interactions of ionic biomolecules (e.g., triphosphates) with metal surfaces. This allows for a remarkable improvement of peak shapes for such analytes and the reliable quantitation of ionic biomolecules, which could not be realized before.

What’s missing from the analytical toolbox?
 

We can generate enormous data sets with huge complexity, but then the data processing is starting to be a bottleneck. We have the instrumentation capable of generating such data sets, but we may have difficulties with the speed and quality of data processing. While reviewing manuscripts or reading articles already published in my field of lipidomics, I have observed frequent problems with identification, quantification, and data reporting. Some people are overwhelmed with the amount of data, which may result in a low quality of published papers even in the leading multidisciplinary journals. I recommend paying more attention to data processing and bioinformatics, which is far behind instrumental developments.

Michal Holcapek is Professor of Analytical Chemistry, Department of Analytical Chemistry, Faculty of Chemical Technology, University of Pardubice, Czech Republic