Maximum effectiveness, minimal side effects, least-possible damage to healthy tissue. Scientists have long pursued cancer treatment offering one or more of these benefits, and a researcher at the University of Tennessee at Chattanooga is now among them.
Michael Danquah is researching a highly precise form of treatment delivery—at the nanoscale, molecular level—to fight leukemia.
Danquah researched vaccine production as a chemical engineering doctoral student and today is director of the chemical engineering program at UTC. He is working with pediatric oncologist Dr. Manoo Bhakta of Erlanger Health System to lead a team of researchers funded by the inaugural $25,000 award of the Collaborative Research Grant initiative, a partnership between UTC, the UT College of Medicine and Erlanger.
They are investigating the use of aptamers—small RNA or DNA molecules that can bind to cellular targets and sometimes called the chemical equivalent of antibodies. Aptamers target “receptors” on the surface of cancer cells. In acute lymphoblastic leukemia (ALL) the type responsible for about 20 percent of all cancer in children and people younger than 20, a unique receptor is found, and Danquah is working on an aptamer to uniquely target that receptor.
“CD19 is a unique receptor, or biomarker, for B-cell acute lymphoblastic leukemia,” Danquah says. “So, after identifying such a unique receptor, the next stage is: Can you molecularly engineer a DNA aptamer? Can you design a DNA aptamer that can specifically target the CD19 on the tumor? It’s all about understanding the features of the target receptor and how to develop or design that aptamer to recognize it.”
A successful aptamer design, in which the molecule binds to the targeted receptor, results in something called a “ligand,” a general term for a molecule that binds specifically to another molecule. “When you have a ligand that can target that specific receptor on the tumor, that’ll be a significant breakthrough because you’ll have something that can actually identify a particular receptor on the tumor,” Danquah says.
Since receiving the $25,000 funding at the end of 2018. Danquah says great progress has already been made. The work has yielded two aptamer designs—one a DNA molecule, the other an RNA molecule—that can target the CD19 receptor. “The next stage is to synthesize these two aptamers and then test the binding mechanism,” Danquah says. “Once that is done, we can incorporate the aptamer into drugs in a process called ‘molecular coupling’ or ‘conjugation.’ You couple the aptamers onto the drug so that the drug is delivered, the aptamer will navigate the drug to the receptor site.”
“The collaboration with Erlanger is fantastic,” Danquah says, “and using the UTC SimCenter we’ve managed to develop the initial models of the aptamer for CD19 that we will study. When we reach the phase of (laboratory studies) and then move to clinical phases, our collaboration with Erlanger will make that happen much more easily because clinical research is what they do.”
In anticipation of the years of work ahead for this project, Danquah will be working with two doctoral students with a similar research focus. “Both students started this fall, and once they’re done with their courses, they will be actively involved, and I’m excited about that,” Danquah says. “The long-term strategy that I have for this project is to be able to build some form of Biomedical Center of Excellence that will be looking into developing new diagnostics and targeted treatment strategies for cancer and advanced pathogen detection systems. When I came to interview to join UTC last year, one of the things that excited me to come here was the opportunity to work with Erlanger.”
Recently, Danquah began collaborating with UTC’s Henry Spratt, a professor and microbiologist, and David Levine, a professor of physical therapy. Spratt and Levine are researching the presence of pathogens in healthcare treatment environments. These microscopic bacteria live on surfaces or may be airborne and cause infection in people exposed to them. With Danquah, Spratt and Levine are examining the possibility of incorporating aptamers in detection of those pathogens.
Meanwhile, Danquah is staying busy looking for funding sources for his research. He has a list of cancer research and prevention funders, including the National Science Foundation, National Institutes of Health and Prevent Cancer Foundation, that he plans to pursue aggressively to support his research. “Since I came here, I’ve been excited about the possibility of building the biomedical research capabilities of UTC so that we can become like a hub, whereby these hospitals and health-care facilities around us can be collaborators and research partners with us to develop emerging biomedical technologies,” Danquah says. “That’s my long-term strategy.”