March 15, 2011

Peer Review: Roden ’12 Researches Testicular Cancer

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As a child, Jamie Roden ’12 loved learning by taking things apart. Whether it was a remote control or a toaster, Roden was fascinated with the way things work. Though her high school in Watervliet, NY, did not offer many advanced courses, Roden was fortunate to have the opportunity to participate in a program called New Visions Scientific Research and World Health at SUNY Albany during her senior year. Throughout the course of the program, Roden was introduced to various types of biomedical research, and became particularly interested in the mechanisms of cancer initiation and progression. After finishing her final project on cancer stem cell theory, Roden was hooked. At Cornell, Roden continued to pursue her interest in cancer research with the help of her mentor, biomedical sciences postdoctoral fellow Dr. Amy Lyndaker who mainly works on testicular germ cell tumors, or TGCTs, research. TGCT is a very curable form of testicular cancer that responds well to chemotherapeutics because its DNA damage response, or DDR, differs from the DNA damage response in other forms of tumors.“Testicular germ cell tumors are exquisitely sensitive to chemotherapy, and more than 90 percent of patients with newly diagnosed TGCTs are cured. Studies of human tumors suggest that the DDR in these germ cell-derived tumors differs from that of tumors of somatic cell origin and that this difference may be linked to their increased chemosensitivity,” Roden said.    Roden and Lyndaker hypothesize that an inactive DDR during early tumorigenesis eliminates selective pressure for mutations in DDR genes. They are currently testing their hypothesis by not only examining the DDR activation status in testicular teratoma samples from an existing “Ter” TGCT mouse model, but also by working to create a new mouse model that is more reflective of the most common types of human testicular malignancies, Roden said.According to Roden, the results obtained from analyzing the DNA damage response activation status in the existing mouse model (obtained from Duke University), have been largely inconclusive because of the nature of the tumors. “The tumors are teratomas –– “monster tumors” –– which have all different kinds of tissues in them. This characteristic makes it very difficult to visualize DDR activation with immunohistochemistry methods, so now we’re trying to look at activation status in a new way–with Western Blots [a widely used analytical technique used to detect specific proteins in the given sample of tissue homogenate or extract by using gel electrophoresis to separate native or denatured proteins by the length of the polypeptide],” Roden said.  Roden hopes that the new mouse model she and Lyndaker are working on will also help ensure more accurate results because the model is made to be similar to the most common types of human testicular tumors. “We knocked out a potent tumor suppressor gene and activated a potent oncogene specifically in the testes with the hopes of creating a mouse cancer model that’s more similar to the most common human tumors. We [actually] just got our first mouse with tumors. Analysis is under way to see what kind of tumors they are,” she said. Roden and Lyndaker’s ultimate goal for the project is to help develop new treatment pathways for deadlier cancers, as well as chemoresistant TGCTs. “In addition, because germ cells share many properties with pluripotent stem cells, these studies may reveal new strategies for eliminating the cancer risk associated with stem cell therapies,” Roden said. Much of her motivation, Roden explained, stems from Lyndaker, whose optimism and enthusiasm is inspirational.  “She’s always really excited and optimistic about her research and has been such a great role model.  Amy has the ability to explain complicated things in a way that makes sense. She [also] seems to do an amazing job balancing her work life and her home life, which is incredibly encouraging to see in a young professional,” she said. Over the last year, Roden has been contemplating what she would like to do after graduating from Cornell and was unsure of whether she wanted to pursue a Ph.D., M.D., or a M.D./Ph.D., but realized that her love of and dedication to research made her decision clear. “I love to interact with people, but could not spend my life solely treating patients, knowing that there could be better treatments to be discovered,” Roden said.  “For a while, the M.D. /Ph.D. degree seemed like the right choice for me, but I have a gut feeling that I’ll ultimately choose the research project over clinic hours any day.”Roden hopes to pursue a Ph.D. in either cancer bioloy or pathobiology and continue to work in an academic setting, such as a research hospital. Roden also wants to dedicate her time to educating others about the importance of science. “Ultimately,” Roden said, “I want to be able to teach, probably at the college level, and run an outreach program that shows middle [and] high school kids that science is awesome and cool and worth considering as a future direction of study.”

Original Author: Maria Minsker