Sarah W. Harcum of Clemson University is leading a team that has received $6 million for research that could help lower the cost of several drugs that run into the thousands of dollars per treatment and fight some of the world's most debilitating ailments.
The team brings together researchers from three states to seek better ways of engineering Chinese hamster ovary cells, which are used to manufacture more than half of biopharmaceuticals.
The potential impact is immense. Products from these cells represent more than $70 billion in sales each year and include drugs for Crohn's disease, severe anemia, breast cancer and multiple sclerosis.
The focus for Harcum and her team will be on the Chinese hamster ovary "cell line."
A cell line is developed from a single cell culture and starts with uniform genetic composition that would ideally remain unchanged. But that genetic composition drifts as the cells reproduce, and they become less effective at creating the drug they have been engineered to create.
As a result, manufacturing becomes more expensive, said Harcum, a professor of bioengineering.
"We expect by the end of the study we will have identified some genes that cause the instability," she said. "What would be even better is if we can prove by modifying those genes we can make a genome that is more stable. With success, the Chinese hamster ovary cell line will stay more stable during the manufacturing. We hope to get that drift to be reduced– that's the ultimate goal."
The four-year grant was among eight awards totaling $41.7 million announced Wednesday by the National Science Foundation's Established Program to Stimulate Competitive Research, or EPSCoR.
The Harcum-led research strikes at the heart of one of the toughest challenges in manufacturing biopharmaceuticals.
Biopharmaceuticals are different from more conventional drugs, such as ibuprofen and acetaminophen, which are based on what researchers call "small molecules" and are relatively easy to manufacture.
Biopharmaceuticals, however, are 1,000 times larger than the small molecules and have structures that are more complicated.
While biopharmaceuticals can treat disease that small-molecule drugs cannot, manufacturing these large-molecule drugs are more difficult. They require more monitoring, control and analysis throughout the manufacturing process.
Harcum and her team are aiming to improve the process not for a single drug, but for a wide range of biopharmaceuticals.
The project is expected to increase patient access to expensive medicines, while helping educate the professionals headed for the advanced biomanufacturing workforce.
As part of the project, researchers are planning to promote diversity on the research team by including several undergraduate and graduate students who are from groups underrepresented in engineering. Also, three tenure-track faculty members from underrepresented groups will be mentored by more senior researchers.
Harcum is the principal investigator on the grant, and she is collaborating with researchers from the University of Delaware, Tulane University and Delaware State University. They are calling the project "Advanced Biomanufacturing: Catalyzing Improved Host Development and High Quality Medicines through Genome to Phenome Predictions."
Co-principal investigators are Kelvin H. Lee, the Gore Professor of Chemical Engineering at the University of Delaware, and Anne S. Robinson, chair of the Department of Chemical and Biomolecular Engineering at Tulane University.
Robert Jones, executive vice president for academic affairs and provost at Clemson, said the project underscores the value of collaboration.
"The grant is helping build a sustainable research infrastructure in three EPSCoR-eligible states, enabling each of the four institutions involved to build on each other's strengths," he said. "Further, the grant helps prepare a diverse talent pool for the biomanufacturing industry. We are well positioned for lasting impact."
Each project in the latest round of EPSCoR awards is focused on understanding the genome-to-phenome relationship. The projects are under EPSCoR's Track-2, which promotes collaboration across jurisdictions.
Chinese hamster ovary, or CHO, cells are used to manufacture biopharmaceuticals because these cells are highly adaptable to growth in different environments, bear no human viruses and are capable of high-level production, Harcum said.
"However, the ability to continually adapt is also a negative attribute because clones may lose the desirable cellular and product phenotype even during during short-term culture," she said. "This is known as cell line instability and is rooted in a relatively unstable genome. Here, we will develop approaches to relate CHO cell genome stability to the phenome and apply this knowledge to improve control over instability of the CHO genome."
Martine LaBerge, chair of the Department of Bioengineering at Clemson, said Harcum's extensive work with CHO cells uniquely qualifies her to lead the project.
"Dr. Harcum has 20 years' experience working with CHO cells and has used genomic approaches to study CHO cells for quite some time," LaBerge said. "She is very well aware of the industrial issues that affect CHO cells."
Anand Gramopadhye, dean of the College of Engineering, Computing and Applied Sciences, said the project addresses some of the nation's most critical needs, while building research infrastructure in three states, with Clemson taking the lead for South Carolina.
"By seeking to engineering better medicines, Dr. Harcum and her team are focused on one of the 21st century's grand challenges," he said. "They are also using this project to enhance diversity in the talent pipeline. The size of the award attests to its crucial importance."
Lee said the grant will help accelerate biopharmaceutical manufacturing in the United States.
"This project will help us address the challenges we face in making these medicines more widely available, which could prove transformational for thousands of patients," he said. "This is a natural extension of the work we are doing as part of NIIMBL."
Lee leads NIIMBL, which is short for the National Institute for Innovation in Manufacturing Biopharmaceuticals. The institute was established in March with a $70-million grant from the National Institute of Standards and Technology in the U.S. Department of Commerce and with support from more than 150 collaborators, including Clemson, Tulane and Delaware State.
Robinson said the EPSCoR project will help create a more diverse workforce in biopharmaceutical manufacturing.
"This team has deep experience in supporting underrepresented groups and is well-suited to mentor diverse junior faculty members and students," she said. "The grant will help support programs that deepen our commitment to creating a more diverse workforce."
Douglas Hirt, associate dean for research and graduate studies in the College of Engineering, Computing and Applied Sciences, said the project helps lay the foundation for a sustainable research enterprise.
"This project strengthens existing collaborations among academics and provides mentoring and development for students and tenure-track faculty at four institutions in South Carolina, Delaware and Louisiana," he said. "The work that Dr. Harcum and her team have initiated has set the stage for success and is to be commended."
Tanju Karanfil, the vice president for research at Clemson, said the grant helps build Clemson's reputation as a world-class research university.
"This EPSCoR grant underscores that the University's researchers continue their pursuit of bold ideas and innovative answers, while affirming Clemson's role as a leader in health innovation," he said. "I congratulate Dr. Harcum and her team on a job well done."