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Applied Biosystems and Dr. Leendert Looijenga

A partnership for the advancement of science

Dr. Leendert Looijenga

Professor in Translational Patho-Oncology, Department of Pathology

Erasmus MC-University Medical Center Rotterdam

Dr. Leendert Looijenga is an expert in the pathobiology of germ cell tumors. Heading up one of the leading research groups in his field, Dr. Looijenga is credited with multiple successful lines of research as well as clinical applications, including a modification of the WHO classification for testicular germ cell tumors.

We recently spoke with Dr. Looijenga about his current work at the Erasmus MC-University Medical Center Rotterdam, and how his collaboration with Applied Biosystems is helping his group rapidly advance their science.

First off, tell us a little about your area of expertise.

I am a medical cell biologist who provides an interface between fundamental research and clinical research. My group at the Erasmus Medical Center is currently studying the development of normal and abnormal germ cells—the stem cells of spermatogenesis in males and oƶgenesis in females. Based on different abnormalities, these cells can be disturbed and give rise to different kinds of cancers. Those cancers are my main field of interest.

What studies are currently underway in your lab?

We are working on the development of tools for early diagnosis of presumed patients, including those with infertility and patients with abnormal development of the gonads. Specifically, we are focusing on the identification of pathways—the genes and proteins—related to these kinds of diseases. We're also investigating why some people respond very well to treatment while others do not, and eventually die of their disease. And we are always active in the development of different animal and culture dish model systems.

How is Applied Biosystems contributing to your work, and how did that collaborative relationship come about?

Applied Biosystems is involved in the analysis of the role of specific microRNAs in the malignant transformation of germ cells. We are working together using high-throughput expression profiling to identify which microRNAs are expressed at different points during normal development and in the various stages of cancer.

As far as how our collaboration came about, it was quite a coincidence. Applied Biosystems delivered a presentation at our institute that covered the high-throughput analysis of microRNAs and messenger RNAs. I knew that Applied Biosystems put very well developed methods and technologies on the market that could be easily leveraged in laboratory activities, so I spoke to the presenter afterwards about initiating a collaborative relationship—they had the technique and we had the samples and the ideas. I was very happy that he agreed and was able to activate this collaboration very quickly. Since then, Applied Biosystems has supported the project wonderfully by bringing the equipment and the know-how into our group, which enables us to work with an excellent set of data in our research.

And are you seeing promising results from that data so far?

Yes. We have found that germ cell tumors can look like tissues that you would see during normal embryonic development in the uterus. So fundamental processes like growth and differentiation are involved, and they are regulated by specific microRNAs that determine whether a protein will be formed.

We have already identified a number of specific microRNAs that are most likely related to the development of this disease. And we have identified one specific microRNA that leads to tumor cells by overriding the mechanism that tells the cell to die if it becomes abnormal due to environmental conditions.

Which Applied Biosystems tools are you using to analyze the microRNAs?

We started with the early access 157 set of mircroRNAs in the high-throughput quantitative PCR approach, which was very informative. We analyzed quite a number of cancers in that setup and identified a number of relevant mircroRNAs. Based on that work, we collaborated further with AB to test the 8x48 pools of microRNAs, so more than 300 microRNAs. Those are as informative as the early access set of data and we are following those new microRNAs in the studies we are doing now. In addition, we tested the normalization set of microRNAs, or small nuclear RNAs, to allow the best analysis of the data from expression profiling.

How quickly are you able to do the analysis?

That's a very important issue. We are able to analyze microRNAs very, very quickly. Using a quantitative approach we can have data available on multiple sets within a week. The analysis is very good because of support by Applied Biosystems for bioinformatics and the availability of normalization tools.

What new collaborations do you see in the future between your lab and Applied Biosystems?

We are currently going through the biological studies and the validation of the role of these microRNAs in the development of cancer, and we are planning our follow-up studies with Applied Biosystems.

Beyond that, I am very interested to know more about the technical progress Applied Biosystems is making in the area of high-throughput expression profiling and the amplification capabilities that will allow us to identify more targets based on a very limited amount of samples. This way we will have a highly efficient way to work on a biological question and optimize a technique on our own. I'm sure that other new developments will arise as well, and that we will incorporate them in the way we do science here.

You certainly have your hands full with all of your current areas of research. Is there a new question you would like to tackle in the coming years?

An important issue for the future is the correlation between copy number of DNA, messenger RNA, microRNA, and protein. I think this is an underdeveloped area of study in every organization, and putting effort into combining those sets of data to derive information about the biological system as a whole will be a wonderful development for the future of cancer research.

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