Cracking Cancer’s Code
Student research projects build on the College’s legacy in unraveling the mysteries of cancer and treating the disease around the globe
It’s a chilly late-winter evening in Lancaster, and classes are over for the day at Franklin & Marshall College. But the lights are still on in a laboratory on the third floor of the Barshinger Life Sciences & Philosophy Building. Working with the fluorescent microscope, flow cytometer and other sophisticated laboratory equipment, Heather Croy ’13 and Andrew Foley ’13 are enthusiastically looking in the smallest of places for some big answers.
Biochemistry and molecular biology majors at F&M, Croy and Foley are part of a team of student researchers under the guidance of Assistant Professor of Biology David Roberts. Together, they are attempting to advance the understanding of how colon cancer cells originate. Their work will result in posters for the College’s Spring Research Fair, where students from the full spectrum of the liberal arts showcase work they’ve completed in collaboration with faculty members. It could also serve as a springboard for medical research years from now.
The students’ experiences in the lab mirror those of numerous F&M alumni who have embarked on careers in cancer research across the United States. And while their research specialties may differ, a common thread is clear: their accounts of how the rigor of F&M’s curriculum and the mentorship of supportive professors served as a powerful combination to launch their careers. It’s a story that alumni across generations know well.
More than half a century before Croy and Foley enrolled at F&M, James Hoeschele, Ph.D., ’59 took his own first steps in a career of research. A pioneering research chemist in the use, role and fate of metal ions and metal complexes in biological and biomedical systems, today his name appears on a dozen U.S. patents and more than 60 publications.
After graduating from F&M in 1959, Hoeschele studied under fellow Fummer Carl Brubaker ’49 as a graduate student at Michigan State University in the 1960s. Brubaker, winner of F&M’s Williamson Medal upon his graduation—the College’s highest award to a graduating senior—helped Hoeschele land a position in a research lab that developed the widely used chemotherapy drug cisplatin. Oncologists use the drug, marketed under the name Platinol, to treat cancer of the bladder, ovaries, testicles and other types of cancer.
Hoeschele later co-invented carboplatin, a chemical analog of cisplatin but equally effective against solid tumors, and less toxic. He says his individualized academic experience at F&M launched his career in research.
“F&M was the perfect place for me in many ways,” Hoeschele says. “I think of the 60 credit hours of chemistry that imbued a deep knowledge and passion for the subject, the significant value the liberal arts education provided in helping me understand what it means to learn, and the influence of people such as Dr. [Fred] Snavely and Professor Ruth Van Horn. When you put them all together, it's one powerful influence.”
Today Hoeschele is emeritus assistant professor of chemistry at Michigan State and adjunct professor of chemistry at Eastern Michigan University. He remains strongly engaged with his alma mater as a member of the John Marshall Society, which includes individuals who have provided significant support to the College’s endowment and annual fund. He created an endowed scholarship for F&M chemistry majors and provides additional support for another need-based scholarship to support and encourage current students in undergraduate work.
Hoeschele is part of a long line of F&M alumni—Amanda Toland, Ph.D., ’90, John Toso, M.D., ’86, and Stacy Murray ’97 among them—who nurtured a passion for science to contribute to cancer research.
Sleuthing for Elusive Answers
Back in the Barshinger Life Sciences & Philosophy Building, Roberts and his students are studying the basic science behind cancer research. Their focus is on one particular gene, adenomatous polyposis coli (APC), which the professor says is mutated in more than 80 percent of all colon cancer cases. “Research suggests it is the first mutation that happens along the path of a cell changing from its normal function in a tissue to ultimately becoming cancerous,” Roberts says.
Their research is conducted with two major systems—human colon cancer cell lines grown in the lab, and the fruit fly Drosophila melanogaster, which provides the only which provides the only current system that can be made completely deficient for APC.
“APC appears to work exactly the same in fruit flies as in humans, so we use them as surrogates for human APC to try and understand how it works,” says Roberts. “We then take the information we learn from the fruit flies and test its applicability to human biology.”
The lab’s results have suggested that some of the prevailing models of APC function are probably not correct, Roberts says. This has opened the door for the students and their mentor to develop their own new models in an effort to understand why colon cancer cells originate.
Croy, who’s from the New York City area, met Roberts when she was a sophomore and looking for an experience to add to her schedule. Roberts suggested she volunteer in his lab, and she’s been there ever since. Like a sleuth attempting to solve a crime, Croy has pursued the identity of an unknown protein thought to be integral to APC’s function. From the moment she first learned of “Protein X,” it has captivated her.
“I remember listening to Dr. Roberts’ presentation in class when he first mentioned that he was looking for this unknown protein,” Croy says. “Oh my gosh, I thought, discovering an unknown protein? That is what I want to do. It’s been so exciting.”
During the summer of 2012, Croy participated in F&M’s Hackman Scholars program in which students conduct challenging, high-level projects to support research by faculty members. She has continued to work in the lab throughout her senior year, and plans to attend medical school next fall.
“My research experience has been incredible,” she says. “It’s a great way to coalesce what you learn in the classroom, read in primary research papers and discover in the lab.”
It’s an experience with which Amanda Toland, who graduated more than two decades ago, is quite familiar. An associate professor in Ohio State University’s Department of Molecular Virology, Immunology and Medical Genetics, Toland oversees research that attempts to better understand genetic susceptibility to cancer. A biology major at F&M, Toland earned her Ph.D. at the University of Utah in human genetics before post-doctoral training in medical genetics and a three-year clinical fellowship at the University of California, San Francisco.
“I experienced high-quality science at F&M that was relevant, and enjoyed many good interactions with faculty,” she says. “I worked on my honors thesis with Professor Nancy Bachman, who showed me what being a scientist is all about. Learning how to read protocols, testing hypotheses and accepting that disappointment is a nearly constant companion were all foundational for success in graduate school and beyond.
Learning How to Learn
Across the lab from Croy, research has been a rewarding challenge for Foley, a highly accomplished student from Hershey, Pa. Foley is a recipient of F&M’s prestigious Rouse Scholarship, which is awarded to Franklin & Marshall students who have demonstrated unusual leadership while achieving academic excellence. His fascination with molecular biology began in Roberts’ “Cell Biology” class, but it was his participation in a “Cancer Biology” seminar with Roberts that focused his curiosity on understanding the signaling pathway and APC’s role in it. Like Croy, Foley’s lab work tackles one of APC’s mysteries.
“At the end of the signaling pathway, there’s an important protein called beta catenin that has to be regulated,” says Foley, who plans to pursue an M.D./Ph.D. degree after college. “In the normal process, it appears that APC plays a role in beta catenin regulation because when APC is mutated, beta catenin levels rise and cancer often results. We’re trying to understand whether APC recruits other proteins to aid in beta catenin regulation. Mutant APC may not be able to recruit these important partners. This would tell us a lot about APC’s role in cancer.”
While Croy and Foley have learned plenty of science along the way, they also realize they’ve learned much more from Roberts and other professors at F&M.
“In the classroom, Dr. Roberts has been inviting and clearly interested in being a good teacher,” Foley says. “In the lab I get to see his passion, and how he makes learning fun. It’s much easier to come into the lab after classes are over for the day and do the hard work because you are watching somebody who enjoys it so much himself.”
Croy agrees. “The enthusiasm and encouragement I’ve gotten from the entire biology department has really enhanced my learning here at F&M,” she says. “I’ve never met someone who has as much patience as Dr. Roberts. He’s always so positive and focused. I’ve gotten comfortable working in the lab and taking the next step on my own, and now I have to [graduate].”
Alumni ‘Passionate About Science’
While Hoeschele helped develop an anti-cancer drug, alumni counterparts Toland, Toso and Murray help meet the needs of those suffering from cancer. These F&M alumni work at the confluence of the laboratory and actual patient care. And just as Croy and Foley are learning, they know that a passion for science is a key to a successful career.
John Toso, director of biopharmaceutical translational medicine at GlaxoSmithKline in Philadelphia, credits a candid conversation with an F&M professor for clarifying his career goals. The professor was Richard Fluck, the College’s Dr. E. Paul and Frances H. Reiff Professor of Biology Emeritus, who challenged Toso to explain why medicine was his career goal.
“At that point I really wasn’t sure,” Toso says. “Dr. Fluck really pushed me to re-evaluate and expand my vision on what I wanted from med school and what I hoped to achieve in medicine. He made me understand that it’s not just a process, that it’s about being passionate about the science and wanting to contribute to that in a significant way.”
Inspired by his introduction to cell biology and microbiology at F&M, Toso attended the University of Pittsburgh’s School of Public Health, where he received a master’s degree in infectious diseases and microbiology before entering Pitt’s medical school. After his residency in pathology and three years working in tumor immunology at the National Cancer Institute, Toso went to GlaxoSmithKline.
Today he is attempting to develop an immunotherapeutic treatment for cancer that will enhance the immune system to have it fight the cancer and eventually cause a tumor to regress. “I’ve followed Dr. Fluck’s advice through each step of my career,” Toso says. “He’s a big reason behind my success.”
For Stacy Murray, a career in cancer research began with an F&M alumni connection. Murray has been building a successful career in the Department of Cancer Prevention, Detection and Control at the Duke University Cancer Center for the past 15 years. A biology major and art minor at F&M, she secured a job in cancer research after reaching out to F&M alumnus Jeremy Sugarman ’88, who put her in touch with a researcher at Duke. For most of her career, Murray has been involved in a variety of epidemiology studies and genetic research, but in December 2012 she transitioned into the regulatory and compliance team overseeing the nearly 100 drug trials currently under way at Duke.
“We have a large and growing research community and ensuring compliance with the Code of U.S. Federal Regulations is increasingly complex,” Murray says. “Ensuring patient rights and following all the proper protocols is different from what I’d been doing before, but it keeps me connected with the patients we’re trying to help, and I like that.”
Murray credits F&M for giving her the tools to succeed in cancer research.
“It’s been a fascinating learning experience, and I am grateful for my F&M biology major to fall back on when delving into the intricacies of leukemia and lymphoma cancer research,” Murray says. “Getting a well-rounded knowledge base from across the liberal arts has enabled me to do what I’ve wanted to do. I learned the ability to analyze, think through an issue and deduce answers.”
In Barshinger, Croy and Foley are learning exactly what Murray means. As they prepare to graduate from F&M, the students reflect on the lessons they’ve learned in the lab—lessons that connect them to many alumni who have proceeded them, and ones that build on Franklin & Marshall’s powerful legacy of learning.
“The most important thing we get out of this research experience, the whole point, really, of the college experience, is learning how to learn,” Foley says. “When you’re presented with something you’ve never seen before, can you figure out what you’re going to do with it, or determine how it functions? Through this research experience, we’ve confronted so many questions and been part of an important conversation. It’s the perfect application of learning how to learn.”
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