Titia de Lange, PhD :: Profile
Leon Hess Professor
The Rockefeller University
New York, NY
Q: How did you become interested in breast cancer research?
A: During my graduate training at the Dutch Cancer Institute and post-doctoral training in Harold Varmus's laboratory at UCSF, I was always working side by side with cancer biologists; I had a lot of exposure to cancer research early on. My own interest is in fundamental questions about how our cells reproduce, stabilize, and repair their DNA. This is an issue relevant to cancer because cancer is a disease caused by changes in our DNA. For instance, the breast cancer genes BRCA1 and BRCA2 are involved in homologous recombination, a kind of DNA repair during copying. We know that breast and ovarian cancers can get their start when either of these two mutated genes fail in their intended job. Later on in my own research, several projects that relate to breast cancer arose out of fundamental biological questions I was asking. For instance, one of our BCRF-funded projects allowed us to study the Rif1 gene, which, like BRCA1 and BRCA2 is involved in homologous recombination. We were able to create a detailed analysis of what this gene does in a cell during this process. If we understand the activities of the genes involved at these vulnerable moments of DNA-copying, we may contribute to new treatments for cells' predictable deficiencies.
Q: Could you describe your recent discovery that may have a positive impact on breast cancer?
A: Our current BCRF-funded project grew out of an interest in the Tel2 gene, which sits at the crossroads of the most important signaling pathways in cells. Now, we are testing whether we can use the Tel2 gene as an additional target to sensitize cancer cells to chemotherapy. We published our research results in the journal Cell in December 2007.
Q: You are known for your discovery and ongoing research on telomeres, the tips of chromosomes that protect our DNA. How is this discovery relevant to cancer?
A: Cancer cells have a way to prevent their telomeres from withering away, as they do in our normal cells. This provides cancer cells with their immortal growth properties and has raised the possibility that we can stop cancer growth by blocking their telomere synthesis. So, our work on telomeres provides a way of understanding how cancer cells survive and reproduce themselves.
Q: How close do you think we are to preventing or finding a cure for breast cancers?
A: I am more optimistic now than I was in the past because of the development of tools to get a full inventory of every genetic change in a cancerous tumor and the efforts to create screening modalities that can reveal the Achilles heel of each type of breast cancer. My hope is that the new information will identify the molecular pathways where interventions will be effective and cancer-specific so that better and less toxic treatments can be developed.
Q: How has BCRF been helpful to you?
A: The BCRF was key for our work on Tel2. Our research on Tel2 began as part of a project funded by a National Institutes of Health grant. We knew that Tel2 to be an important gene but our hypothesis about its functions turned out to be wrong (which is not unusual in my experience). Luckily, we learned something unexpected and important in the process: Tel2 affects a critical nutrient-sensing pathway called mTOR. mTOR is already being explored in the clinic as an important breast cancer target. But our NIH funding did not support this type of research and we would have stopped working on it if it hadn't been for the BCRF funding.
Q: What are the biggest challenges in cancer research today?
A: To mine the avalanche of new genetic information coming our way and use the new insights to make sense of the cancer cell and intervene in ways that help real people in their struggles withdisease.
Q: Did you ever consider another kind of career than that of the sciences?
A: I am not good at anything else, so I don't really have a choice. I don't recall ever choosing science as a "career." For me, science is not a career or work; it is a (well-paid!) hobby which I enjoy, every day. I consider myself extremely lucky because I don't have to work.
Q: What advice would you give to young researchers?
A:Do what you think is fun and interesting in science. Don't follow the herd. Focus on research that excites you and put the fundability concerns second.
Read more about Dr. de Lange's current research projects funded by BCRF.