Introducing Gerlinde Wernig: Apfelstrudel Meets Microscope

bridges vol. 22, July 2009 / News from the Network: Austrian Researchers Abroad

By Linda Krempl



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Dr. Gerlinde Wernig

Time is very limited in Gerlinde Wernig's life, but she and her husband still don't want to miss the pleasure of homemade Apfelstrudel, so she got herself an apple "peeling-and-cutting" machine with which she proudly claims to make an Apfelstrudel with 6 kg of apples in half an hour! It is enjoyable to hear this energetic woman, who currently works at the Institute of Stem Cell Biology and Regenerative Medicine at Stanford University, while finishing her surgical pathology medical training, talking as enthusiastically about her apple peeler-corer as she does about her work. Grasping things instead of quarreling about them seems to have given Gerlinde Wernig a competitive edge throughout her career and in her daily routine.

Coming from a strong family background in the humanities, Gerlinde decided to study law and moved to Vienna after high school. Having come from Braunau, a small town in Upper Austria, she enjoyed her academic years in the city and it was in Vienna that she met her future husband, Marius Wernig. However, after her first year of studies, she was not happy to continue learning laws and regulations. She realized that, given her fascination with biology and her preference for literally taking things into her own hands, studying medicine would be much more in line with her aptitudes. Marius, who had already been enrolled at the medical university in Vienna for a year, was a bit bewildered at first by Gerlinde's change of plans, but the following years demonstrated the benefits of exchanging and sharing their medical knowledge in different but often overlapping fields.

In their relationship Gerlinde was the one who, from the onset, focused on receiving training in internal medicine, while Marius felt more attracted to doing laboratory research (click here to read the introduction of Austrian Scientist Dr. Marius Wernig, Associate Professor of Pathology at the Institute of Stem Cell Biology and Regenerative Medicine at Stanford University).

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Gerlinde and Marius Wernig

When Marius, encouraged by superior research opportunities, decided to go to Munich, Germany, Gerlinde tried to move with him. But changing universities from Austria to Germany was a difficult matter, so the two medical students had a commuter relationship for three years and Gerlinde ended up finishig her degree in Vienna before she was offered a place in Germany. To gain experience in the lab, she opted to do a master's thesis for which she received a scholarship from the Medical University, Vienna.

Both having earned their M.D. degrees,  the couple tried to apply for jobs in Europe in the same city.  Once again, after Marius had accepted a postdoctoral offer in Bonn, it was a delicate matter for Gerlinde to come along, this time in search of a medical training program position. With a smirking tone, Gerlinde recalls that people in Germany were very suspicious about her reasons for moving and working in Germany. But once she managed to get a position for internal medical training in Bonn, she appreciated working at the university clinic; most of the time they had to treat patients with highly specialized problems and it was at this point that she fell for hematology.

Hematology: the science encompassing the medical study of the blood and blood-producing organs.

 

While completing a summer internship in New York at the end of her studies in Vienna, Gerlinde had encountered the American approach to scientific training and truly relished it. Impressed by the positive interactions between professors and their students, and the US emphasis on excellent teaching, after four years in Bonn the couple decided to leave Europe and try to continue their careers across the pond.  But once more, moving to another country and trying to find a position to continue her medical training was a real hurdle for Gerlinde. Unlike Marius, who received a scholarship as he had published persuasive papers in Bonn, there was no financial support for Gerlinde to complete her medical training.

But she made best of her situation, and while studying for the USMLE (United States Medical Licensing Examination) in order to qualify to continue her clinical training, she worked as a fellow in the Hematology Department at the Brigham and Women's Hospital . Along with training first-year medical students in the lab, Gerlinde managed, together with her research team, to publish in top-notch journals in the following years.



Outstanding scientific work - from Harvard to Stanford

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Blood smear from a patient with Chronic Myeloid Leukemia (CML).


Trying to cure or avoid the outbreak of cancer, new approaches called "molecularly targeted therapy" have recently been attempted. Instead of fighting cancer cells by administering conventional chemotherapies, which often lead to severe systemic side effects, scientists target the genetic defects by blocking the disease-triggering mutations with "small molecule inhibitors" in order to uproot the cancer at its source. This kind of treatment has been first established for treatment of chronic myeloid leukemia (CML) therapy with imatinib (Gleevec ) only a couple of years ago and has become the gold standard in treatment of disorders involving tyrosine kinases given as an oral therapy.

Leukemia: any of various acute or chronic neoplastic diseases of the bone marrow in which unrestrained proliferation of white blood cells occurs, usually accompanied by anemia, impaired blood clotting, and enlargement of the lymph nodes, liver, and spleen.  
PV (Polycythemia Vera): a form of myelofibrosis, a rare disease of the bone marrow in which collagen builds up fibrous scar tissue inside the marrow cavity. This is caused by the uncontrolled growth of a blood cell precursor, which results in accumulation of scar tissue in the bone marrow, characterized by an overproduction of blood cells leading to leukemia. 


Focused on the genetics of leukemia, Gerlinde's team in Boston succeeded in finding a JAK2 protein kinase mutation, which occurs in a high proportion of patients suffering from myeloproliferative disorders such as polycythemia vera (PV)(95%), essential thrombocytosis and myelofibrosis.

 
Subsequently, they managed to implement this mutation in a so-called mouse model and recapitulate features of the disease. And it was Gerlinde and her colleagues who evaluated 11 different "small molecule inhibitors" provided through a non-profit platform with major pharmaceutical companies suitable to "target" this specific mutation not only in vitro but also in vivo . Within a remarkably short period of time, it took only 3 years from discovery of the genetic defect to the implementation of the phase I clinical trials, her team was able to prove the relevance of this mutation to the disease, soon followed by demonstrating the therapeutic efficacy of one out of many inhibitor molecule in a murine model of PV. Promising clinical drug trials in humans currently in phase II in 3 centers in the US (Dana Faber , Mayo Clinics and Stanford ) have already been initiated.  Gerlinde Wernig recalled that it was a very time-consuming venture, especially because rodents have a comparatively long life cycle of their erythrocytes and many inhibitors with suitable properties in vitro did not have any major effect in vivo. Also they needed to treat the mice orally, as this is the gold standard of care in analogy to imatinib/CML. "But finally we ended up with a compound with some good properties," said Gerlinde about her selective small-molecule inhibitor.

Her findings were published in Cancer Cell (2008; click here to access the article).  Soon afterwards, she received a tempting offer from Dr. Irving Weissman , director of the Institute of Stem Cells and Regenerative Medicine at Stanford who works within the same field, to continue her training in surgical pathology and join his lab. Even though both Marius and Gerlinde had already accepted another position in Boston, they reconsidered their situation and finally moved to the West Coast.  Comparing the eastern to the western side of the US, Harvard versus Stanford, Gerlinde (who considers herself a city person) misses Boston as a city but enjoys Stanford (a 40-minute drive from San Francisco) for its collaborative scientific exchange. She has found that, at Stanford, people from all different scientific fields constantly run into each other, not only exchanging their thoughts and ideas in the lab, but also sharing private activities. Thus, Gerlinde and Marius have recently joined a road cycling group with some Stanford colleagues and, in case they have a free Saturday morning, enjoy cycling along the magnificent coastline.

Speaking of the constant pressure experienced while working in a hot field, Gerlinde grinned and stated: "Well, you have to be good, you have to be fast, you have to be innovative - but at least there is research money available for such promising fields and it is more fun to make things happening and moving along!" During the last few years she has become accustomed to the constant challenge of unstable working positions and fellowship applications for salary support (she got awarded a special fellow from the leukemia and lymphoma society), but Gerlinde also looks at the bright side of this issue: "Every year you have to rethink if you still like what you are currently doing." She added, "I will move backward or forward - wherever we will find the best research and living conditions. And, if this happens to be in Austria, of course I will go back, but last time I tried, it did not work out!" A slight regret sounds in her voice, remembering how people from a department at the medical university of Vienna were unable to offer her an adequate position when she and Marius tried to return to Austria last year.


Unconventional ways to make things work

As the question arose, as to whether she would recommend that other women choose the rather expensive option of cryopreserving stem cells from their baby's cord blood, Gerlinde revealed that she would definitely invest the money and mentioned en passant that Marius and she are expecting - a little boy due in one month.
Cryopreservation: a process by which cells or whole tissues are preserved by cooling to low temperatures, such as (typically) 77 K or -196°C (the boiling point of liquid nitrogen). At these low temperatures, any biological activity, including the biochemical reactions that would lead to cell death, is effectively stopped. Unlike in the past, when the umbilical cord was discarded following birth, today’s parents have the option of freezing the stem cells from the umbilical cord blood at their own expense for their own children; or they can also donate them. Umbilical cord stem cells retain the ability to differentiate or change into other types of cells in the body, and are promising for curing or at least improving some diseases.)

 

When Gerlinde was asked how she plans to continue her demanding training with a baby - taking a longer break is not an option as she would drop out of her program - she hesitated briefly. But after a moment she continued, habitually optimistic, planning that with the support of Marius and a nanny they will be able to meet this challenge. And Gerlinde, seemingly never tired of finding a way to make things work, has already arranged for a microscope so she will be able to work at night from home...


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The author, Linda Krempl, is a food science and biotechnology scientist and former intern at the Office of Science & Technology at the Embassy of Austria in Washington, DC.




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