A researcher at the University of Colorado at Boulder and the University of Colorado Cancer Center competed against more than 400 U.S. scientists to win one of 13 highly sought after Stand Up to Cancer Innovative Research Grants.
Hang "Hubert" Yin, assistant professor of chemistry and biochemistry at CU-Boulder, will receive $750,000 over three years for his "high-risk, high-reward" research project -- high-risk because it challenges the way cancer science is currently being done, and high-reward because of its potential for saving lives.
"We asked our best and brightest young researchers to step outside their comfort zones and strive to make big differences with bold initiatives," said Dr. Richard D. Kolodner, chairman of the Stand Up to Cancer grants review committee. "If these projects come to fruition, some of the ideas could be game-changers in cancer research."
Yin's project will focus on the Epstein-Barr virus, which benignly infects about 90 percent of all humans, but is also at play in various types of lymphomas -- post-transplant or AIDS-related lymphoma, Burkitt's lymphoma and Hodgkin's lymphoma.
"EBV hijacks certain white blood cells called B cells and makes them cancerous, but little is known about how the process happens because we have no way of probing the protein that regulates EBV's activities," Yin said.
Proteins, Yin explained, are agents of action in human systems. About a quarter to a third of human's half-million proteins are associated with cellular membranes, the thin layers of phospholipids that act as barriers of our cells. These membrane proteins play pivotal roles in many biological processes, including cancer development, making them excellent targets for drugs.
"Walk into any drugstore and about 60 to 70 percent of the drugs you can buy work against membrane proteins because scientists know how they work and therefore are more readily targeted," he said. "For isolated proteins like LMP-1, the protein that activates EBV, we do not have tools for accessing parts that are embedded in the membrane, so we don't know how they work and can't develop targeting drugs."
Protein-targeting drugs such as Avastin, a VEGF inhibitor, or Iressa, an EGFR inhibitor, for non-small cell lung cancer, or Herceptin for breast cancer, are one of the hottest trends in cancer treatment. They act as very specific keys to trigger cells to die or make them more susceptible to traditional treatments with few of the side effects cancer treatments are known for.
Yin, a biochemist and chemical biologist, is a member of the Colorado Initiative in Molecular Biotechnology directed by Nobel laureate Thomas Cech at CU-Boulder and the developmental therapeutics team led by Dr. Gail Eckhardt at the University of Colorado Cancer Center. His project combines chemistry, biotechnology development and computer science to build a new tool to probe the inaccessible proteins for information.
"To design a probe to target a protein, you have to understand how the protein interacts with its environment," he said. "The computer allows us to simulate the membrane environment, which is hard to study using other conventional methods. The integration of different technologies hopefully will render a viable design for a probe of membrane proteins."
There is a risk that Yin will fail in making the probe -- after all, few before him have tried because of the sheer difficulty -- but he is confident he can do it, and that when he does, the tool will unlock a critical door for scientists studying all types of human disease, not just cancer.
"If we are successful, we are going to have a very powerful tool that researchers could use to study the 25 to 30 percent of human proteins that are not accessible currently, where you could name any protein, and we can provide a specific tool with which you can study it." he said. "We can then think about new methods of treatment and prevention for lymphoma and other diseases. That's the high reward. Science can move slowly, then take giant leaps ahead. This tool could be the giant leap ahead."
When the probe is designed, Yin said, he will collaborate with other scientists at the University of Colorado Cancer Center to test it in cell and animal models, and eventually bring it to market, either as a tool to develop a drug that targets the EBV-initiated lymphomas or a treatment in itself.
"I am privileged to be part of the University of Colorado system with its robust Cancer Center and the CIMB at Boulder," Yin said. "My senior colleagues, in particular Tom Cech and CIMB co-director Leslie Leinwand, encourage young people like me to think outside of the box in a funding system where being a risk-taker sometimes isn't very favored."
It would be challenging for Yin to receive major funding for an early-stage project like this outside of the Stand Up to Cancer Innovative Research Grants program. Traditional science funding requires what Kolodner calls "a demonstrable expectation of success, which means that some of the research has to be done before an investigator can submit a proposal. There are not many opportunities to receive funding for cancer research where young scientists are freed from the requirement of having 'proof of concept' data in order to receive grants, and certainly not such large grants."
Yin and the other 12 young researchers -- from renowned cancer research institutions such as the Dana-Farber Cancer Institute, Stanford University and Fred Hutchinson Cancer Center -- received funding for projects that represent new approaches to the most important and challenging problems facing cancer researchers today. Each funded project has potential to significantly advance the identification of the complex mechanisms that cause cancers to occur and spread; to lead to the development of a new generation of targeted treatments; and to improve the methods of diagnosing cancers and monitoring the effects of treatment, according to Stand Up to Cancer officials.
The Innovative Research Grants Program's funding comes from Stand Up to Cancer, a collaboration between the American Association for Cancer Research and the Entertainment Industry Foundation that raises money to hasten the pace of groundbreaking translational research that can get new therapies to patients quickly and save lives. The 45-member Stand Up to Cancer grants review committee considered 412 projects in an intense, multistep evaluation process that narrowed the group to 73 semifinalists, then to 19 finalists who made in-person presentations. From that group, the committee selected the 13 recipients. Learn more about the Stand Up to Cancer initiative at www.su2c.org.
The University of Colorado Cancer Center is the Rocky Mountain region's only National Cancer Institute-designated comprehensive cancer center. Headquartered on the University of Colorado Denver Anschutz Medical Campus, UCCC is a consortium of three state universities (Colorado State University, University of Colorado at Boulder and University of Colorado Denver) and five institutions (The Children's Hospital, Denver Health, Denver VA Medical Center, National Jewish Health and University of Colorado Hospital). Learn more at http://www.uccc.info.
The Colorado Initiative in Molecular Biotechnology has a mission to foster new research, teaching, and technology development at the interface of life sciences, physical sciences, mathematics, computational sciences, and engineering. The focus of this initiative is to understand and manipulate living cells and control cellular behavior through a global analysis of molecular events using methods that span a continuum from basic to applied research.