Biomedical Research is Making a Difference in Patient Outcomes
by Cassie Montgomery
Researchers in Auburn University’s Samuel Ginn College of Engineering are delving into some of the world’s most challenging health issues with the goal of improving patient outcomes by understanding underlying health disparities, improving personalized medicine and expanding access to medical advances to the developing world. Auburn College of Engineering faculty are advancing fundamental knowledge and technology in the fields of biomedical engineering and health systems, and they are backed by some of the biggest agencies in the industry, including the National Institutes of Health and the National Institutes of General Medical Sciences.
As one of the college’s five research focus areas, research in biomedical engineering and health sciences accounted for nearly $3.5 million in extramural research awards in 2021, and the potential for growth in this arena is exponential.
“The work our faculty have undertaken in the biomedical engineering and health science fields will undoubtedly change the world and make an immeasurable difference in people’s daily lives,” said Interim Dean of Engineering Steve Taylor. “Our researchers across the Samuel Ginn College of Engineering are developing new technologies and taking novel approaches to solve health care’s most pressing problems, leading to more cost-effective treatment options, faster diagnostic results and, ultimately, better patient outcomes.”
Understanding Underlying Health Disparities
Colorectal cancer is the third most common non-skin-related cancer and the third leading cause of cancer-related mortality in the United States. Obesity is directly linked to an increased risk of death from colorectal cancer. Although overall colorectal cancer incidence rates declined from 1991 to 2011, they have risen recently in younger age groups and remain high in states with a high incidence of obesity.
Researchers and doctors acknowledge there is an established link between colorectal cancer diagnosis and obesity, but understanding why that link is present and how best to treat such a dual diagnosis is still not fully understood. Thanks to a nearly $2.5 million R01 research award from the National Institutes of Health, an interdisciplinary team from three universities led by Elizabeth Lipke, the Mary and John H. Sanders Professor in Auburn Engineering’s Department of Chemical Engineering, and Michael Greene, associate professor in Auburn’s Department of Nutritional Sciences in the College of Human Sciences, will examine this link and aim to understand how best to treat these patients to improve clinical outcomes.
Lipke, whose expertise lies in tissue engineering, and Greene, whose research focuses on metabolic diseases, are co-principal investigators on the project and have enlisted the partnership of collaborators Xu Wang, assistant professor of pathology at Auburn’s College of Veterinary Medicine; Amit Mitra, assistant professor of drug discovery and development in Auburn’s Harrison College of Pharmacy; Dr. Drew Gunnels (Department of Surgery), Robert Oster (Department of Medicine) and Jim Mobley (Division of Molecular and Translational Biomedicine) of the University of Alabama at Birmingham; and Dr. Marty Heslin, executive director of the Mitchell Cancer Center at the University of South Alabama.
Further collaboration and support for the work was provided by the Auburn University Research Initiative in Cancer, prior NIH funding and the University of Alabama at Birmingham Center for Clinical and Translational Science, of which Auburn University is a member. Additionally, graduate and undergraduate students in chemical engineering and nutrition have been and will continue to be engaged at all levels of the project.
Through their combined expertise, the team aims to develop a toolset for explaining a pathological link between obesity and colorectal cancer tumor progression.
While the research behind this work has been ongoing for several years, for this new stage of the project, the research team is expanding their data collection through hospital partnerships to include actual patient data. Combined with information gleaned from studying how the tumors behave in laboratory settings in animals and in 3D engineered tissues in petri dishes, this expanded approach has the potential to provide a better understanding of the role of obesity-associated factors in modulating the tumor microenvironment in colorectal cancer disease progression.
“We have a hypothesis that it’s not simply obesity and colorectal cancer, but there are different types of colorectal cancer. So it could be that obesity is driving different types of colorectal cancer in different ways,” Greene said. “One possible outcome of this work is personalizing treatment. Understanding the disease better for personalized treatment would definitely be a big picture outcome of this work from a physiological point of view.”
Lipke agreed and expanded on the potential impact on how patients are treated in the future.
“Being able to understand if we can create models that replicate the patient tumor microenvironment closely enough to inform treatment decision making is important,” Lipke said. “Every patient wishes that there was an answer to the question, ‘What’s going to be the outcome of this treatment for me?’ Up until now, most of the model systems for trying to predict individual outcomes haven’t been very helpful. We have to be really careful in model design and characterization to see how far we can get in making that a possibility. By using engineered tissues, we can refine the environment that the cells are experiencing in the dish, making it more like what they experienced in the human body.”
Improving patient outcomes is a primary goal of their work, but the two also aim to address health disparities associated with both colon cancer and obesity based on geographic populations in the future.
Improving Patient Outcomes Through Personalized Medicine
Personalizing medicine and therapeutics to an individual patient has the potential to address many health issues, from cancer and cardiovascular disease to fighting antibiotic resistant bacteria. Through the work of chemical engineering assistant professors Robert Pantazes and Panagiotis Mistriotis—both supported through R35 National Institutes of General Medical Sciences Maximizing Investigators’ Research Awards of $1.75 million and $1.89 million, respectively—advances in personalized medicine are on the horizon.
“There are a lot of different ways this research could be applied, and one of them is cancer. We could do DNA sequencing of the cancer and then design treatments specifically to target whatever genetic variation a patient has,” Pantazes said. “Another application could be for antibiotic resistant bacteria—things like MRSA. Antibiotic-resistant bacteria work through what are known as escape mutations, where the bacteria acquire some change that helps it escape the treatment. That shows up in the DNA. If we can sequence the DNA and apply the technology we’re working on, you could design a treatment in response to the mutating antibiotic-resistant bacteria.”
Pantazes’s research focuses on developing and experimentally testing computational methods to design therapeutic proteins. In his lab, he and his graduate students are examining how to design antibodies better and faster than traditional approaches. They will then expand beyond antibodies to other types of proteins that have the potential to allow physicians to treat diseases more quickly than with established strategies.
“Over the next 10 years, what I would like to do is get to a point where we can reliably and consistently design a protein to bind to whatever we want it to bind to,” Pantazes said. “The goal of my career is to develop an effective computational method to design proteins for whatever purpose someone might want to use them for.”
Mistriotis’s approach lies in the field of mechanobiology and will further examine fundamental cellular processes to develop novel therapeutic interventions against the initiation and progression of pathophysiological phenomena, including cardiovascular disease, aging and cancer. As a field of study, mechanobiology is concerned with the mechanisms by which cells sense and respond to mechanical signals. Mistriotis noted that cells in the human body are constantly subjected to these signals, but researchers aim to learn more about how these signals impact cell behavior.
“The widely held view is that cells can sense and respond to these cues, but our understanding of the underlying mechanisms remains very limited,” he said. “Our lab explores how physical forces convert into biochemical signals to influence cell behavior.”
Expanding Access to the Developing World
The future of vaccine development is going to be faster, cheaper and more geared toward the needs of the developing world. The technology behind the vaccines of the future will be impacted by the work of Chris Kieslich, assistant professor of chemical engineering.
Kieslich is the Department of Chemical Engineering’s latest recipient of the R35 Maximizing Investigators’ Research Award (MIRA) from the National Institute of General Medical Sciences.
Kieslich’s five-year, $1.87 million award for his work titled “Development of computational tools for accounting for host variability in predicting T-cell epitopes” marks the department’s third MIRA in two years, alongside Mistriotis and Pantazes.
“What we’re working on through computation is making tools that would be useful for designing new vaccines with a variety of applications that could be developed faster or cheaper because they’re easier to produce and store,” Kieslich said. “In very basic terms, we are developing tools that understand the interactions between a pathogen, such as a virus or bacteria, and the receptors in the immune system.”
The MIRA funding will allow his research team stability and flexibility to enhance scientific productivity and the chances for important research breakthroughs.
“Take COVID for example. So much of the data we have is from the Western world and because of that, the models perform very well for people of those genetic backgrounds, but not so much with other parts of the world,” Kieslich said. “Part of what we’re trying to do is develop our models in a way that will allow us to make it accessible for larger parts of the population.
“Having a platform or a way of developing vaccines that can be tailored for a specific population or individual is a huge possible outcome of our research but we’re really starting at the basic science,” Kieslich added.