Fighting Cancer, Learning Engineering
Dr. Sachin Patil (standing) and senior Cassidy Kerezsi studied computational models of two proteins. They hypothesized that a drug molecule can bind to one of the proteins to help the body fight cancer.
By Jennifer Kitchen '11
When Cassidy Kerezsi finished her freshman year at Widener, she wanted to jump start her plans for a career in biomedical engineering. Although the Chichester, Pennsylvania, resident didn’t land an internship as she hoped, she found a promising opportunity on campus. She volunteered to help Dr. Sachin Patil, assistant professor of chemical engineering, research cancer-fighting drugs.
Patil, a Widener faculty member since 2010, established a NanoBio Laboratory, a place in Kirkbride Hall where students interested in discovery and design of targeted delivery of groundbreaking drugs could gain hands-on research experience. “I hoped that students with enough discipline could take their in-class experience to the next level by applying their knowledge to research projects like this,” Patil said.
Kerezsi spent the summer of 2013 working with Patil. She studied computational research software and analyzed potential molecules in support of his hypothesis on an inventive approach to fighting cancer known in the biomedical field as novel molecule discovery.
The result? It was far beyond what one would normally expect from a summer project involving a rising sophomore. Patil and Kerezsi discovered that a high-blood pressure drug helped a natural protein in the body kill cancer cells. They ultimately published their findings in a paper in a peer-reviewed, international biomedical journal, and their work has the potential to make huge impacts on the fight against cancer. “This discovery could serve as a novel lead molecule for the development of more potential inhibitors against a variety of cancers,” Patil said.
Dr. Fred Akl, dean of the School of Engineering, said this accomplishment achieves two of the key goals in Widener’s long-range plan. “Cassidy’s involvement in research with Dr. Patil exemplifies Widener’s commitment to experiential learning and rigorous academics,” he said.
The fight against cancer that Patil and Kerezsi joined is an ancient battle. Cancer is one of the oldest and largest public health challenges in the world, dating back to 3,000 B.C. In the United States, it accounts for approximately 25 percent of deaths annually and costs the economy more than two hundred billion dollars every year. It will develop in one in two men and one in three women over their lifetimes.
Patil and Kerezsi said the current available treatments for cancer are limited to toxic drugs that have serious side effects leading to secondary cancers at times. “While these treatments exist to fight cancer, none have the ability to be completely successful all of the time,” Kerezsi said.
So, why hasn’t the human body begun fighting back? Patil’s research explains that it has been—it just hasn’t been successful.
“Our bodies have found something to fight cancer,” Kerezsi said. “It is a protein (p53), known to cause cancer cell death. However, cancer also has a protein (MDM2) that binds with this cancer-fighting protein, preventing it from doing its job—killing the cancer cells. This happens because of its unique shape, which creates a lock and key formation with the cancer-fighting protein.”
Armed with this information, Patil and Kerezsi set out to identify novel molecules with the potential to be developed into selective, non-genotoxic cancer drugs. “Specifically, we planned to discover novel compounds that will effectively bind and inactivate the bad protein that is produced by almost all of the cancers,” he said.
Patil’s research hypothesis was to find a molecule that would “trick” the MDM2 protein into binding with it, leaving the p53 protein free to kill the cancer cells.
As part of this project, FDA-approved drugs from the Drug Bank database were screened using ultrafast shape recognition (USR), a virtual screening technique, with the help of a researcher in England, Dr. Pedro Ballester of the University of Cambridge. “These computational methods helped us query molecules to identify a drug that could inhibit the MDM2 cancer protein based on molecular shape and binding ability,” Kerezsi said. “This would allow the p53 protein to do its job: fight cancer.”
They found six compounds that matched the criteria. “We then tested on real, human colon cancer cells,” she said. “We found a drug—Telmisartan, an anti-hypertension drug—that inhibited colon cancer growth by 50 percent over a two-day period.”
Patil said Telmisartan has a long history of safe human use and thus may present an immediate clinical potential as a cancer therapeutic. After the Widener research, The National Cancer Institute tested the drug on 60 different types of cancer and found results similar to the effect on colon cancer.
Kerezsi and Patil, along with Ballester, wrote a paper on their findings titled “Prospective Virtual Screening for Novel p–53–MDM2 Inhibitors Using Ultrafast Shape Recognition” that was published in the Journal of Computer-Aided Molecular Design, a journal which reports new and original research and applications, in February 2014.
Kerezsi was amazed to learn how significant the findings were. She never considered that her work would be anything more than volunteering in a lab. “Working with Dr. Patil has been a once in a lifetime experience,” she said. “He puts his students first and wants to see us succeed.”
Kerezsi is not the only student Patil has mentored at Widener. There are currently ten students who serve as volunteers in the NanoBio lab. He has also advised two senior project groups that have explored similar protein interaction within cancer cells, one of which has submitted a manuscript to the Journal of Computer-Aided Molecular Design for their work with Fluspirilene, an approved anti-psychotic drug, which emerged as a potential p53-MDM2 inhibitor.
Patil and Akl hope that showcasing these students’ rigorous academic skills in getting published throughout their careers at Widener will help fund additional research opportunities, as well as highlight what the School of Engineering aspires to for its students. “Undergraduate research allows students to reach their best potential and to broaden their horizons beyond what they learn in the classroom,” Akl said. “Students such as Cassidy are inspired by working with faculty on pioneering research and often continue their quest for innovation and discovery following their graduation from Widener.”
Outside of the lab, Kerezsi, who in addition to majoring in biomedical engineering is earning minors in chemical and mechanical engineering, is a math tutor. She is also a member of the Widener Honors program, Engineers Without Borders, Society of Women Engineers, and the biomedical engineering organization.
In the fall, she can be found on the volleyball court. She has played for Widener since her freshman year. It was one of the reasons she chose Widener—that and the four-year co-op program that allows students to work in a co-op job and graduate in four years.
“I knew I wanted to study biomedical engineering,” she said. “It is the perfect combination of math, science, and medicine—everything I wanted to study. I never thought that I would have opportunities like this research project during my time in college, and I never imagined that I’d have a chance to support the fight against cancer in such a significant way.”
Patil believes that this project is only just the beginning for Kerezsi. “It was wonderful to have a student like Cassidy participate in research of this caliber as a sophomore,” he said. “She has set herself up for success in the field of biomedical engineering early on. She is a quick learner. I envision her taking the cancer research work she is currently carrying out to a whole new level.”
For additional information on Patil’s NanoBio Laboratory, visit: http://www.sachinpatil.org.