Introducing Claudia Petritsch – Gaining Ground in Glioma Research 

bridges, vol. 31, October 2011 / News from the Network: Austrian Researchers Abroad

By Martina Stadlbauer

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Dr. Claudia Petritsch

“There is no cure for glioma, yet. This type of brain tumor can be so aggressive that it kills patients within a year,” says Claudia Petritsch, an assistant professor in the Department of Neurological Surgery at the University of California, San Francisco (UCSF). With her team, Petritsch investigates the cellular origins of brain tumors and how these cells turn from normal brain cells into brain tumor cells. Just a few weeks ago, in September, Petrisch published her most recent research findings in an article titled “Asymmetry-Defective Oligodendrocyte Progenitors Are Glioma Precursors” in the journal Cancer Cell.

Her research was made possible by the collaborative culture at UCSF, as Petritsch points out. Her lab is situated at the Helen Diller Cancer Research Center but also is affiliated with the Brain Tumor Research Center and Department of Neurological Surgery and the Eli and Edythe Broad Center of Regeneration Medicine. These affiliations, where doctors and scientists are in contact with each other on a daily basis, allow for great collaborative work, she says. “The neuro-oncologists work really well together with basic researchers. This creates an interplay of translational and basic research – I don’t see patients but I see their doctors,” says Petritsch. “There is always an open door; I can go to tumor board and hear the neuro-oncologists discussing their patients and they come to our basic research seminars. Moreover, we get surgical tissue from brain tumor patients on the day of the operation for our analyses. Seeing the frustration of the doctors about lacking efficient treatment motivates us lab researchers to work towards a better understanding of this terrible disease. My lab does its share by helping to understand the role that stem and progenitor cells play in gliomas.”

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The challenge of treating brain tumors

There are many reasons why certain kinds of brain tumors are particularly difficult to treat. Some tumors are simply inoperable due to their size or location in the brain. One of the biggest challenges is to reach all the malignant tumor cells either with surgery or radiation and to find a way to avoid or fight drug resistance of the cells when using chemotherapy. This is why research on the origin of the mutated cells that cause these tumors is crucial, in order to gain greater insight into tumor genesis.

Claudia Petritsch and her group are studying the dark side of stem and progenitor cells, which is their contribution to the genesis of brain tumors. The lab is addressing the questions: Which type of cells are the origin of glioma and how do these cells turn from normal brain cells to brain tumor cells?

In the brain, as in most tissues, adult or tissue stem cells can be found which are responsible for regeneration or remodeling of these tissues. So-called progenitor cells are similar to stem cells but are already more specific and can only develop into a limited number and type of cells. Stem cells and – as the Petritsch lab recently showed – glial progenitor cells, can divide either symmetrically or asymmetrically. A symmetric division generates two identical daughter cells. When stem cells divide asymmetrically, they produce one daughter cell that remains a stem cell and the other becomes a more differentiated progenitor cell.

An oligodendrocyte, a type of cell in the central nervous system, visualized by green fluorescent protein (GFP).

The Petritsch lab recently discovered that oligodendrocyte progenitor cells taken from human brain surgical samples undergo mostly asymmetric divisions when there is no pathology. By contrast, when oligodendrocyte progenitors are taken from patients’ brain tumor tissue, these tumor cells switch gears and undergo more symmetric cell division. The purpose of asymmetric cell divisions in the normal brain and symmetric cell divisions in brain tumors is difficult to study in human brain samples because they are scarce.

Therefore, Petritsch and her group turned to murine brain cells and glioma models to follow the cell division modes of progenitor cells and their functional significance at distinct steps of tumor development. They could prove that normal oligodendrocyte progenitors indeed undergo asymmetric cell division to generate a balanced number of proliferative and differentiating cells. They then documented that oligodendrocyte progenitor cells divide more symmetrically and expand rather than differentiate in brains that will later develop tumors, compared to healthy brains. Since these cells are also present in large numbers in the tumors themselves, the researchers concluded that these symmetrically dividing cells must be the cellular origin of the glioma.

To summarize: In the healthy brain, oligodendrocyte progenitors divide asymmetrically to self-renew and differentiate into oligodendrocytes, the support of nerve cells, with a one-to-one ratio. This is important to replace aging brain cells. The large proliferative potential of oligodendrocyte progenitors is, however, dangerous. When the cells lose asymmetry and shift towards symmetric divisions, these cells expand too much, probably acquire additional mutations, and turn into tumor cells. Thus, as presented in the Cancer Cell article mentioned above, Petritsch and her group identified this change as a novel switch by which mammalian brain cells turn into brain tumor cells. The lab now uses basic research to identify important regulators of the switch and evaluates them as molecular targets to which potent anti-glioma therapies can be targeted.

The making of a scientist

Petritsch started her scientific career in Vienna where, after studying molecular biology and biochemistry at the Vienna BioCenter, she received a diploma fellowship as well as a Ph.D. fellowship at the Institute of Molecular Pathology (IMP).

As a diploma student, she was working at the IMP in the field of signal transduction (a process by which a signal molecule causes one or many responses inside a cell) where they discovered that the molecules they were working with play a very important role in cancer. After spending some time in the lab of Hartmut Beug, who was focusing on progenitor cells at a time when stem cell research was far less popular than it is today, Petritsch came across an article on asymmetric cell division by Yuh Nung Jan that sparked her curiosity. She wanted to work on this and so applied to his lab at UCSF, where she started working on neural stem cells in 1997. Petritsch describes the following years as a very important and formative time in her life, where she enjoyed and benefited from the collaboration with many bright and productive scientists.

Proposition 71 of 2004: $3 billion was guaranteed over the next decade to support stem cell research in the state of California.

When Petritsch left Austria, she had planned to stay away for only two to three years, but she stayed at UCSF for six years – first as a postdoctoral fellow and then as a postdoctoral researcher. In 2002 when she started looking for something new, her attention was drawn to the Gene Center and Department of Biochemistry at the Ludwig Maximilian University in Munich, Germany. At that time, the Gene Center seemed like a perfect fit for her, with her interest in developmental and stem cell biology. At the Gene Center she was working on asymmetric cell division and, after about two years, they made some discoveries suggesting that the genes they were working on really had a connection to cancer. That was when she got interested in cancer research again and made the decision to return to California; there, in 2004, the California Stem Cell Research and Cures Act (Proposition 71) was passed, guaranteeing funding of $3 billion over the next decade to support stem cell research. “When Proposition 71 was passed in California, a large chunk of taxpayers’ money was committed to do the type of stem cell research that had then been previously prohibited by the Bush administration. I thought being part of this larger pioneering stem cell group and combining my research with something more translational was really attractive, so I decided to go back to California.”

This decision to return to the US was not without challenges for her. In Munich she already had a lab and a team, and at first when she returned to the US she didn’t have either of them. “It was a very difficult decision giving up a fully functioning lab in Germany, but in hindsight it was a very rewarding experience,” says Petritsch.

When she returned to the US, she applied successfully for funds from private foundations like the National Brain Tumor Foundation or the American Brain Tumor Association, and the Neurosurgery Department at UCSF matched those grants with start-up funding. With these funds, she was able to build her lab. Petritsch gathered enough data to apply to the National Cancer Institute and was awarded an RO1 grant as a Principal Investigator. Her team is currently searching for postdocs and students to join the lab and has already hired students from the Vienna BioCenter. More recently, they were also able to attract funding from a biotech start-up, Targenics, which is interested in targeting malignant stem cells with novel immunotherapies.

Claudia Petritsch is not only a successful scientist, but also a great example of a woman who manages to have both a career and a family life. She has a husband, two children, and a dog; and despite her time-consuming job, she manages to spend time cooking or helping her children with their homework. “It was said 12 years ago, at an alumni meeting of an important European scientific organization, that women have to make a decision between a career in science or having children. It seems to me that nowadays having a family is not such a question of principle any more, where you have to make a decision between family and career. It is rather a question of resources and support to manage childcare and having the determination and energy to do it all. As every scientist knows, it’s not a job you can turn off at night. It needs a lot of energy and time to write a really significant and competitive grant proposal or manuscript, and when you get sucked into it there is not time for much else.”

Thanks to the dedication and great collaboration of doctors and scientists, the prognosis for brain tumor patients can be improved. As Petrisch says: “I think that we are really at a very important time where many resources go into brain tumor research and they will turn out to be fruitful. Once all that is currently cooking in brain tumor labs, including ours, comes to the clinic, this will increase tumor patients’ life spans.”


This article is based on an interview conducted by the author, Martina Stadlbauer, with Claudia Petritsch, associate professor in the Department Neurological Surgery at the University of California, San Francisco (UCSF). {/access}