There is no shortage of research taking place at Kean’s New Jersey Center for Science, Technology and Mathematics (NJCSTM). This week, the investigators of one such study, “Repurposing Old Drugs for New Uses: Targeting Multidrug Resistance in Cancer,” took a trip to Washington, D.C., as part of Posters on the Hill, the Council on Undergraduate Research’s (CUR) 16th annual undergraduate poster session.
“Repurposing Old Drugs for New Uses” is a student-faculty initiative led by Dr. Sonia Arora, assistant professor for NJCSTM and the project's principal investigator, and includes senior biomedicine students Christine Chen of Iselin, N.J. and Khushbu Solanki of South Brunswick, N.J., and Ramanpreet Kaur, a junior molecular biology major of Hillside, N.J.
The study was one of only 75 accepted to present at this prestigious national event for which approximately 850 proposals were submitted from colleges and universities around the country. The project was chosen on the basis of its intellectual and scientific merit, as well as its overall significance to the general community. Posters on the Hill seeks to demonstrate the value of undergraduate research by way of the words and stories of students themselves while ensuring that those in the U.S. Congress who provide funding for research and education have a clear understanding of the programs they fund and why these programs are important.
“It was an honor to be able to attend this event and to meet the nation's leaders,” said Kaur, who, along with Dr. Arora, represented the research team at the poster session. “It is not very often that students have the opportunity to meet with their senators and congressman who fund research and discuss the importance of the research they do. That, and knowing that our discussions with members of Congress will impact the future of undergraduate research funding and education, is very exciting." New Jersey Congressmen Rush Holt and a legislative correspondent of Senator Robert Menendez were among those with whom they spoke.
According to the research team, “Repurposing Old Drugs for New Uses” identifies new uses for drugs already approved by the FDA (Food and Drug Administration). The target under investigation is P-glycoprotein (P-gp), a protein pump that transports drugs out of a cell, causing multidrug resistance in cancer cells. The primary objective of the study is to identify a new modulator of P-gp that binds and inhibits its activity, thereby reversing multidrug resistance and causing successful destruction of cancer cells.
“It’s incredible to imagine that a drug which already exists on the market to treat an ailment as simple as a runny nose, for example, can potentially target and help treat cancer cells,” said Kaur, who is studying to become a pharmacist.
The approaches used involve the integration of computational chemistry, structural bioinformatics and cell biology. Using computational chemistry tools, a virtual database of 1,600 FDA-approved compounds was constructed from the Johns Hopkins Clinical Compound Library. The database was then screened for binding to P-gp using structural bioinformatics techniques. The docked orientation of each compound was then analyzed to predict the binding affinity and interactions with the P-gp binding pocket. Finally, cell culture and in vitro techniques were applied to verify the in silico results.
“I enjoy the unique approach of the research, since it comprises both a computational and a cell culture aspect using the wet laboratory,” said Chen, who will attend medical school this fall in pursuit of a degree in internal medicine. “This research particularly interests me because it deals with oncology research – a topic relevant to today's healthcare field – and one that reminds me that I am capable of making a difference through my research.”
Dr. Arora agrees. “The major scope of the project lies in its likely impact on the society by providing a newer treatment option for drug-resistant cancers,” she said, noting that the development of multidrug resistance to chemotherapeutic agents is a major problem for successful cancer treatment. “Multidrug resistance is typified by the broad cross-resistance to structurally dissimilar cytotoxic agents—in other words, the development of resistance by a cell to one drug produces similar resistance to other drugs. This project thus addresses the urgent need to discover new therapeutic agents that reverse multi-drug resistance in tumors, thereby increasing therapeutic potential of anti-cancer drugs,” she said.
A constant source of insight and support for the project, Dr. Jeffrey Toney, vice president for academic affairs, said the possibilities of this research are endless. “Could an antibiotic be used for cancer? Could a psychiatric drug be used to treat obesity, diabetes?,” he said, noting that Dr. Arora's project is “a great example of collaborative research, with emphasis on teaching undergraduate students about the process of scientific discovery.”
Funding for “Repurposing Old Drugs for New Uses” is provided by a Presidential Challenge Grant from Kean University, Ronald E. McNair Program and Merck-AAAS Undergraduate Science Research Program.
Pictured (left to right) are Khushbu Solanki, Christine Chen, Dr. Sonia Arora and Ramanpreet Kaur.