The use of chemotherapy to fight various forms of cancer in the human body has been a successful method for decades, but what happens when it fails? This question strikes a personal note for Martin Pearce, a Ph.D. candidate in the Department of Environmental and Molecular Toxicology at Oregon state University. Prior to his graduate work, both of his grandmothers were diagnosed with breast cancer. One successfully went through treatment and although the other initially responded well to chemotherapy, years later the cancer cells reappeared and there was no other treatment available.
The academic system in the United Kingdom, from where Martin hails, encourages undergraduate students to take what is termed a “placement year” between their second and third years to gain practical experience. At the time of his grandmother’s returning prognosis, Martin was in the second year of his studies at University of the West of England Bristol which had a connection with East Carolina University in the States. Although deviating somewhat from his initial advanced level courses in business, the opportunity to work full time in a biomedical sciences lab at a university renowned for its medical research provided just the right place for Martin to spend the following year.
Martin’s time in North Carolina was not only practical but a reminder of his experience with biology in secondary school. His teacher was a doctor and she encouraged him to pursue a career in a biomedical field. While biology wasn’t his easiest subject, Martin was inspired by his mentor and enjoyed the challenge. Today, he is fully committed to this challenge as a key member in Dr. Siva Kolluri’s Cancer Biology lab group at Oregon State University researching new strategies to target the cancer cells that continue to grow after treatment with chemotherapeutic agents.
Their work involves screening tens of thousands of compounds against such resistant cancer cells that express a particular group of proteins called the Bcl-2 family of proteins. The lab has discovered a novel compound that binds specifically to the Bcl-2 family of proteins that are consistently expressed in therapy-resistant cancer cells and cause them to change shape. One of the fundamental principles of cell and molecular biology is the relationship between structure and function. Change the structure of a molecule and its function within a cell can completely transform. In the case of the Bcl-2 family of proteins, this literally means life or death for the cell.
Protected within the typical expression of a Bcl-2 protein is a region Martin describes as a “death domain”; if this domain is exposed, it induces cell death. Cell death or ‘apoptosis’ is a naturally occurring process in biology. Without apoptosis in the early stages of human development, we would all have webbed fingers! Martin and his team have discovered a compound capable of binding to a Bcl-2 protein, causing it to unfold and expose its death domain. Thus, the protein transforms from one that protects the resistant cancer cell into one that kills it.
Demonstrating the effectiveness of this pathway at the cellular level is remarkable, but Martin explains even the years it has taken to reach this stage are just the beginning of a very long process until it can be used to treat people with cancer. Beyond discovery, through the work of his Ph.D. Martin has realized other critical steps in developing effective cancer treatments that occur outside of the lab. For example, once a compound has been identified that successfully binds to a target protein, medical researchers must work with a patent attorney to protect their work and generate funding. Without patent protection, new drugs can’t be developed.
The dedication to ‘translational research’ or science that is specifically designed to be applied in improving health outcomes is what drew Martin to work with Dr. Kolluri in the first place and continues to inspire his plans for the future. Drawing back to his early interest in business, after finishing his Ph.D., Martin intends to explore a career as a patent attorney.
“This way I can be involved in the most exciting part of the process for me and be a part of people being at the edge of achieving what I was initially inspired in this career to achieve.“
To hear more about Martin’s graduate work and insights into translational research, tune in on Sunday, October 13th at 7 PM on KBVR 88.7 FM, live stream the show at http://www.orangemedianetwork.com/kbvr_fm/, or download our podcast on iTunes!