by Christoph Plass, Ph.D.
Volume 1/Number 2
| I’ve been spending the past several weeks thinking about my father. He was a hearty and generous man, a man of conviction and integrity. He was born in Germany in 1926, studied agriculture, and with my mother raised three children there. I’ve been thinking of him so much because he died recently of lymphoma, the very disease I study so closely. The irony is not lost upon me: This, the very year I receive a scholarship from the Leukemia and Lymphoma Society and the V Foundation Translational Research Award, I lose something so dear to my heart. We work so hard, and then things like this happen. Life can sometimes feel quite chaotic.
So, unlike many others, while I cannot say the loss of someone close to me originally inspired my decision to study cancer genetics, I can surely say my father’s death has given me a sense of urgency I hadn’t quite felt before – at least not so intimately.
Someone once asked me why I like genetics so much, and I suppose it’s because of its inherent logic. There is something very appealing about its clear and orderly presentation of life. On one hand, if genes perform as they are supposed to, all is well. On the other, if certain genes mutate or change – if they don’t follow the rules – things go wrong, setting the stage for cancer or other diseases. There are many aspects of genetics that are predictable; understanding it is a matter of focus and study. Don’t get me wrong, I have always liked mystery, and I know there are many things we cannot explain – at least not yet. But I am convinced, at least at this point, that even though cancer is extraordinarily complex, it is a problem that can be solved, and it is clear that support from organizations like The V Foundation can help us do it.
We have to start small. When I was younger, I worked with yeast, the fruit fly and the mouse. Animal models are very helpful in helping us understand cancer. When I was young, I wanted to be a farmer, but by the time I was studying at the Medical University of Lübeck, I had already dedicated myself to genetics. In 1997, I was thrilled to accept an invitation to join a group of human cancer geneticists at The Ohio State University. It finally became possible to apply the knowledge I had gained in animal models to humans!
I am interested in all aspects of carcinogenesis, but increasingly, I am spending my time studying a process called methylation. In cancer research, it is well accepted that genetic defects lead to tumorigenesis.  | | Dr. Christoff Plass and fellow OSU research team members, who were awarded V Foundation Translational Grant earlier this year. (L-R): Dr. Gregory Otterson, Dr. Christoph Plass, and Dr. Ming You. | Yet we also know that cancer can arise through epigenetic defects as well. Epigenetic alterations are those that do not change the genetic code, but do have an effect on the expression of genes. Methylation, the addition of a methyl group to cytosine, is an epigenetic event. DNA methylation, for example, can silence tumor suppressor genes. In my earlier research, my laboratory developed a technique called Restriction Landmark Genomic Scanning that allowed us to search for DNA methylation defects across the entire mouse genome. The move to Ohio enabled me to use the same technique to study aberrant DNA methylation patterns in human cancers. In doing so, we made a remarkable discovery - that different cancers yield distinct methylation patterns, a mthylation “fingerprint,” if you will. And the majority of cancers we have studied that show changes in DNA methylation also reveal changes in the expression of the nearby genes.
Our findings have important implications for clinical work. Epigenetic defects in cancer are reversible. This is not the case for genetic defects that change the DNA code. If it is possible to reverse methylation, it should be possible to reactivate the adjacent tumor suppressor gene – and this should subsequently slow down the tumor growth. We are now testing this strategy in the clinic, and we are quite excited to think this may pave the way to a novel approach to cancer treatment.
My research is currently focused in three areas. First, we are trying to understand the molecular defects that lead to changes in DNA methylation in cancer. For this project, we are planning to study known genes involved in the DNA methylation pathway, including DNA methylases and demethylases. Second, we are evaluating DNA methylation as a tag for the identification of novel candidate tumor suppressor genes in lung cancer and leukemia. Sites of DNA methylation will be located on the chromosomes and these data correlated with data of other genetic lesions. Third, it is now well established that DNA methylation plays a key role during tumor progression. Since DNA methylation is involved in gene regulation, we hypothesize that tumor type specific methylation of promoter sequences can be used as a molecular marker for the classification of tumors.
When I go to my lab every day, I’m aware that cancer is a problem – a very big, extraordinarily complex problem. But I feel we are slowly making progress in solving it. It cannot come too soon; I feel my father’s presence, and many others’, with me. | ..............................................................................................................................
Editor's Note: | | Dr. Plass is an assistant professor in the Division of Human Cancer Genetics at The Ohio State University. Born in Bremen, he grew up in Emsdetten, served briefly in the German army, and then pursued studies in biology and genetics at the Free University in Berlin and the Medical University of Lübeck before pursuing a postdoctoral fellowship at the Roswell Park Cancer Institute in New York. He joined the faculty at Ohio State in 1997, and, when not writing or in the laboratory, enjoys biking and traveling with his wife Ute. |
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