Pelotonia Fellowships Fund Young Cancer Researchers
BY BOB HECKER
In today’s economy, students with bright ideas for cancer research have virtually no hope of obtaining government grants to support their work.
OSUCCC Director and James CEO Michael A. Caligiuri, MD, says this could discourage the next generation of great scientists from pursuing careers in cancer research that could lead to cures.
But the Pelotonia Fellowship Program gives Ohio State students at all levels of scholarship a chance to start their projects in the labs of faculty mentors.
Administrative Director Jeff Mason says $5 million in Pelotonia funds has been committed to date to the program, which has awarded 173 grants to 74 undergrads, 44 graduate students and three medical students, as well as 10 international scholars and 42 postdoctoral fellows from around the world.
The grants go to students in any discipline who want to conduct cancer research under the guidance of an Ohio State faculty mentor.
Grants are awarded by a faculty committee chaired by Gustavo Leone, PhD, associate director for basic research at the OSUCCC – James. Awards are based on each applicant’s strengths and research potential, the mentor’s qualifications and training record, and the potential impact of the project.
Leone is impressed by the program’s track record. “I’m particularly inspired by how many accomplishments our Pelotonia Fellows have had in such a short time,” he says. “They are making discoveries, publishing their work, receiving larger awards and movingon to productive careers in research. It’s amazing how much they can accomplish at such a young age when given the right tools.”
Here are profiles of three Pelotonia fellowship recipients – an undergraduate, a graduate and a postdoctoral fellow.
Earning a Pelotonia fellowship enabled Taylor Brooks, a senior in Molecular Genetics, to leave his part-time job and devote that time to research that may translate to immunological therapeutic strategies for pancreatic cancer.
“My experiments focus on pancreatic cancer due to its poor prognosis, with less than five percent of patients surviving longer than five years,” says Brooks, who works in the lab of William Carson III, MD, associate director for clinical research at the OSUCCC – James.
Brooks says one possible cause of poor outcomes is the inhibition of the body’s natural immune response by an overabundance of myeloid-derived suppressor cells (MDSCs).
“MDSCs constitute less than five percent of circulating cells in healthy individuals but are increased in blood, lymph nodes and tumors of patients with pancreatic cancer,” he says, explaining that these cells promote cancer spread by inhibiting other cells that would normally destroy tumors.
“Dr. Carson’s team is studying ways to inhibit MDSCs, but it is difficult to obtain enough of these cells to conduct even the most basic experiments,” Brooks says.
Since starting his fellowship, Brooks has employed a cell culture system capable of generating a continuously dividing population of MDSCs. “We are generating these suppressive cells and immortalzing them. Immortalizing MDSCs allows us to study them and understand their role in pancreatic cancer. This may enable researchers to develop drugs that deplete these cells or inhibit their function.”
Brooks, who rode in Pelotonia 12 and plans to ride this year, aspires to attend medical school and pursue a career in oncology and translational research.
He describes his fellowship opportunity as transformative. “I spend time in a lab doing real science that may one day go toward helping a person.”
Some 30 percent of cancer patients in the United States experience cachexia, a severe wasting of body fat and muscle that indicates poor tolerance to treatment and a higher risk of death.
Kara Kliewer, a graduate student in Ohio State’s Nutrition PhD program, is using her Pelotonia fellowship to study how body fat is lost in cancer and to understand changes in metabolism that occur with this disease. Her mentor is Martha Belury, PhD, of the Molecular Carcinogenesis and Chemoprevention Program at the OSUCCC – James.
“Many researchers studying cachexia focus on mechanisms of wasting within muscle tissue,” Kliewer says. “However, a recent study of cachexia using genetically altered mice showed that inhibiting the breakdown of fat preserved muscle mass.
“This suggested to me that cachexia may originate in fat tissue, that cross-talk between fat and muscle tissue is important to maintaining body mass, and that pharmacological inhibition of fat breakdown may be a therapeutic strategy to ameliorate wasting in some cases of cachexia.”
Kliewer is using an animal model of cancer-induced cachexia to characterize mechanisms of fat loss. She hopes her findings will lead to therapies for treating cachexia and extending survival.
After she earns her PhD, she wants to continue studying fat metabolism as a postdoctoral researcher and later in a government lab or industry.
“I am grateful to have received a Pelotonia fellowship,” says Kliewer, who has ridden in the past two Pelotonias and plans to ride this year. “Studies like mine are often poorly funded by government agencies. But decades of research have shown that weight loss affects survival and tolerance to cancer treatments, so studies like this can help improve patients’ lives.”
Yuh-Ying Yeh, PhD
Although promising therapies are arising for chronic lymphocytic leukemia (CLL), the disease remains incurable as patients eventually develop drug resistance and have no good treatment options.
Yuh-Ying Yeh, PhD, a postdoctoral researcher in the lab of John C. Byrd, MD, director of the Division of Hematology, is using her Pelotonia fellowship to understand a natural process called autophagy as a mechanism of drug resistance in CLL.
Autophagy literally means “to eat the self.” It is a process that cells use during periods of starvation to derive energy by breaking down unneeded or dysfunctional components. It also plays an important role in cell growth and development and helps cells maintain a balanced life.
But Yeh says evidence has shown a link between autophagy and multiple human diseases, including cancer. One of her projects involves studying drug action and resistance of flavopiridol, which is under phase I/II clinical trial development for treating CLL.
“Our data showed that flavopiridol induced autophagy in CLL B cells and that inhibition of autophagy can enhance flavopiridol cytotoxicity in CLL,” Yeh says. “I’m investigating the molecular mechanisms of flavopiridol-activated autophagy to develop therapeutic agents for better clinical outcomes.”
Her work is making an impact. “Combined with microarray data and molecular biology validation, we have found that an autophagy protein could provide us with a therapeutic target to specific autophagy inhibitors,” Yeh explains. “We also have generated flavopiridol-resistant cell lines to assist our in vitro studies in understanding drug resistance.”
Yeh, a native of Taiwan, says her goal is to become an independent translational researcher either in academia or industrial settings.
She has become more passionate about her research while participating in Pelotonia events, from fundraising to the bike ride itself. “I have met so many people who devote themselves to fighting cancer in different ways, and we all share one goal: to end cancer.