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Holger Kirsten: Genotyping for the Clinic

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Title: Graduate Research Associate, University of Leipzig

Education: PhD candidate, University of Leipzig (since 2003)

Recommended by: Peter Ahnert

When Holger Kirsten evaluates technology, such as the mass spec-based genotyping tools used in his lab, he doesn't just think about how well it works in the lab — he's also looking at how robust the instrumentation is and asking whether it will fit in a clinical setting.

Kirsten knows that the final goal for even the basic research going into association studies and SNP tracking is to hit the clinic and have a real impact on the medical treatment people receive. A member of Peter Ahnert's molecular diagnostics lab at the University of Leipzig, Holger and his colleagues are working to uncover the genetic mechanisms behind common but complex diseases, such as rheumatoid arthritis and systematic sclerosis. They use various technologies, including what Kirsten calls “mid-throughput MALDI-TOF” and tandem mass spectrometry, to evaluate genotypes and carry out association studies.

Kirsten says the lab currently doesn't have the power to do whole-genome association studies, so he and his teammates are using the candidate gene approach. In one project, he's studying about 30 candidate genes in a population of about 500 samples. Kirsten notes that complexity increases in bridging genetic characteristics with phenotypic ones, and that's an area he'd like to see become more tractable in the field. A disease like rheumatoid arthritis, for instance, is likely to be detectable as several different genetic subtypes which are confusingly presenting in patients as a single phenotype. Treatment options and efficacy stand to improve by leaps and bounds if scientistists and clinicians can clear that hurdle.

It's that very view of disease as a complex connection between genotype and phenotype that lured Kirsten into this scientific path, he says. As his work — and the research going on in the rest of the community — progresses, he hopes to see a continued emphasis being placed on the integration of “genomic data with the mRNA and expression data and with network construction” to really get a comprehensive and clear view of how diseases function. “That's a very exciting and also demanding aspect of getting new knowledge,” he says.

Kirsten credits Ahnert, his lab head, with providing an environment that encourages innovation and scientific exploration. “If you've got an idea, you get a certain amount of resources to follow [that] idea” — even if it's not really related to the focus of the rest of the lab's work, he says.

Looking ahead

This community places a high priority on both collaboration and open access, two values that Kirsten has taken to heart. He believes that the pharmacogenomics field will succeed only if “different groups really pool their resources together … to understand or be able to detect complex disease,” he says. But he also knows that collaborations are only as good as the data they have access to, so he encourages all researchers to make their data as openly available as possible. He notes that his group publishes data from its experiments — “even the primary data from the first experiment,” he says.

Publications of note

Kirsten is first author on a paper titled “Robustness of single-base extension against mismatches,” currently in press at the Journal of Molecular Medicine. Earlier this year, he was first author on another paper, this one in BioTechniques. Entitled “CalcDalton: a tool for multiplex genotyping primer design for single-base extension reactions using cleavable primers,” that paper came out in February 2006.

And the Nobel goes to…

Kirsten skips right past the Nobel for scientific or medical achievement. If he wins the Nobel, he'd like it to be the peace prize, he says.

— MWS

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