OUR STORY

SUCCESS STORIES

Ludwig has a long history of pioneering cancer discoveries. Today, Ludwig scientists around the world are collaborating on new projects, and on ways to move breakthroughs toward the ultimate goal of patient benefit. These are some of the novel ways Ludwig researchers have teamed up to advance our understanding and control of cancer.

Role Model: Q&A with Karen Oegema, Member at Ludwig San Diego

How did you become interested in molecular cell biology?
I went to Caltech, where I majored in chemical engineering, but I had a crisis of conscience in my senior year when I saw the kind of research my friends were doing-watching bubbles rise through glycerol or collecting emissions from the top of fast food restaurants. It made me think back to working in my dad's lab when I was in high school-he is a proteoglycan biochemist who specializes in orthopedic surgery research-and I realized that I wanted to do basic research in a field related to biology.

So, I decided to go to graduate school at University of California, San Francisco (UCSF). During my first year at UCSF, I was influenced by the amazing group of cell biologists that were working on the cell cycle and the cytoskeleton there at that time, particularly Tim Mitchison, Bruce Alberts, Mark Kirschner, Ron Vale, Andrew Murray and David Morgan. This was the time when people were just beginning to develop methods to visualize the cytoskeleton and membrane trafficking in living cells, and the breathtaking beauty of cell structure got me hooked. I joined Bruce's lab because of the emphasis of his group on biochemistry and the attraction of being able to develop parallel means to study processes in vitro and in vivo. After Bruce left to become president of the National Academy of Sciences, I worked with Tim Mitchison, who became a major mentor and scientific role model for me.

Can you give a layperson's description of your research?
We focus on how cells structurally remodel themselves as they divide and how similar kinds of shape changes are involved in the formation of tissues during development. One of our main projects is aimed at understanding how the microtubule-based machine that segregates the chromosomes also directs the remodeling of the cell cortex to partition the contents of the mother cell into the two daughter cells during cytokinesis. We are also very interested in centrosomes, which are the major microtubule-organizing centers in animal cells. We want to understand how centrosomes duplicate precisely once per cell cycle, and how centrosomes contribute to cell physiology. A common feature of cancer cells is the presence of extra, or supernumerary, centrosomes, and we would like to know how this misregulation occurs and whether therapies targeting centrosome duplication could enable the selective killing of cancer cells.

What advances do you see in the coming decade as a result of the work you're doing?
One avenue that we are excited about is the result of a collaboration with the Small Molecule Discovery (SMD) group within Ludwig. Working with the SMD group has allowed us to develop an inhibitor of a key kinase that controls centrosome duplication, which we are calling centrinone. Treatment with centrinone depletes centrosomes from cells. This led to some surprising findings, because we found that cancer cells will continue to divide if you remove their centrosomes, whereas normal cells have a checkpoint that stops them from continuing to proliferate if centrosomes are removed. In ongoing work, we are trying to use this as the basis for a strategy to selectively target cancer cells by combining centrinone with other inhibitors that specifically kill cells dividing in the absence of centrosomes.

What keeps you motivated and excited about your research?
In science you're always trying to figure out how to go from where you are to someplace new. Doing research is essentially like solving a puzzle, and I love the process of trying to solve that puzzle­ because there's nothing more exciting to me than tackling a question and eventually getting an answer.

What advice would you give to a young scientist?
Science is a lot like playing in a jazz band or doing improvisational comedy. A lot depends on the interplay between you and the people around you. I would advise that before you accept a job you should meet the people you will be interacting with, and once you are there, get out and really use your environment to help develop the science that you want to do. The environment you're in is very important. Being at Ludwig has really shaped the type of research my lab is doing. The lab is engaged in curiosity-driven science, and even though it's very focused on solving fundamental cellular questions, the questions we address also have the potential to contribute to the development of cancer chemotherapeutics.

What has been the most exciting discovery of your career?
That's a tough one, but I think it might be the most recent one in which we found, using the inhibitor that we developed in collaboration with the Ludwig SMD group, that normal cells require centrosomes to maintain their commitment to proliferation. This finding was completely unexpected.

Prior to this, the only way to remove centrosomes was to destroy them with a laser or to remove them surgically. The problem with those methods is that the cells have pathways that can regenerate the centrosomes. Thus, you can only remove centrosomes for part of the cell cycle before they are regenerated. What the chemical inhibitor allowed us to do was to suppress the formation of centrosomes so that the cells were unable to form new centrosomes for multiple cell cycles, which revealed that they are essential to the division of normal cells.

Women are three times less likely than men to become scientists. Why is this?
I don't know to what extent women really are less likely to be scientists than men. Women have always been interested in science and have always contributed to the endeavor of expanding human knowledge. If you look back at historical images of labs, you will see that there were many women working at the bench and making important observations that drove things forward, and this is even more true today. However it is clear that women have been less likely to be the principal investigators that get credit and represent the science to the world.

With respect to why men have been more prominently at the forefront in presenting scientific findings, I think it results from the same societal issues that have led to the paucity of female CEOs and political leaders. As these societal barriers are reduced, there are other issues that prevent women from assuming leadership positions in science, including the fact that women are likely to be more heavily involved in the lives of their children and more likely to be the ones responsible for organizing family structure and carrying the cultural torch. Having a family and running a lab is wholly consuming and does not leave a lot of time for much else.

People who want to maintain a sense of balance in their life either need to find a way to work with their partner, family and friends to achieve this, or accept that they are not going to have the same sense of balance that many of the families around them have. Like most women principal investigators, I do a combination of these things. Ultimately, I am also okay with not having a balanced life. There are many things that I should do that I don't. With respect to my children, I think the most important thing is for them to see me pursuing and being successful in doing something that I'm passionate about, and for me to work to enable them to be able to develop and pursue their passions as well.

Does being married to another scientist make it easier to have both?
Definitely. Arshad and I are both very involved in the lives of our children and our careers. We also have an amazing nanny who is very central to our lives. Not only does she understand our personalities, but she's instrumental in pulling our lives together.And our kids love her. One advantage of being married to a scientist is that we can both appreciate the challenges of a career in science; it has also helped to drive our science forward. We both find it invaluable to have someone who provides honest strategic feedback on how we can improve the direction of a project.

What's your favorite paper of all the ones you've published?
That's like asking someone to pick their favorite child. I'm not sure you can really do that. For me, my favorite papers are always the ones I am working on now, because you're obsessed with thinking about the experiments that you've done, trying to put them into context, figuring out what they mean and how to tell the story-whereas the ones that you've already published, they're already behind you.