Charting paths to combat disease

We are constantly bombarded by stimulation in the form of light, sound, heat, pressure and other environmental factors. These stimuli come and go with varied frequencies and durations, but they can induce lasting genetic changes to the cells in our bodies.

“They are called epigenetic changes, and they can lead to the production of specific proteins that can be helpful or harmful to us,” says Abhinav Acharya, an assistant professor of chemical engineering in the Ira A. Fulton Schools of Engineering at Arizona State University.

Acharya is also an immunoengineer who applies the perspectives and skills of engineering to expand scientific understanding of the human immune system. Specifically, he explores how metabolic pathways affect our immune cells.

Metabolic pathways are biochemical reactions that deliver the energy necessary to keep us alive. The process happens through the action of metabolites, which are small molecules that support the generation of energy in each cell of our bodies. Additionally, they can emit signals and modify cell function.

“However, it is very difficult to study how metabolites induce epigenetic changes that alter protein production,” Acharya says. “One of the biggest challenges in this field is to learn how to visualize and quantify these metabolite-protein complexes.”

Doing so could enable the development of vaccines to treat diseases such as cancer and rheumatoid arthritis. So Acharya is leading a new research project to develop techniques that will make these outcomes possible.

His novel approach is supported by a 2022 National Science Foundation Faculty Early Career Development Program (CAREER) award. CAREER award recognition is reserved for young researchers who show the potential to be academic role models and advance the missions of their organizations. Awardees each receive approximately $500,000 distributed across five years to further their work.

Acharya and his laboratory team, including doctoral students Joslyn Mangal and Sahil Inamdar, are focused on developing new techniques to engineer metabolites into nanoparticles made of polymers they are producing from polyester chemistries and ionic bond chemistries. These metabolite nanoparticles will then be delivered for consumption by specialized immune cells called dendritic cells.

“We are working with dendritic cells because they form the bridge between innate and adaptive immunity,” Acharya says. “This means they are directly responsible for generating a response against pathogens such as bacteria and viruses, but they also educate the immune system so that future bacterial and viral attacks are thwarted.”

After the dendritic cells feed on these nanoparticles, Acharya and his team will study three aspects of the metabolites — glycolysis, the pentose phosphate pathway and the Krebs cycle — to determine how they are connected to epigenetic changes in the cells.

“This work will significantly advance scientific understanding of energy metabolite-mediated changes in immune cells,” Acharya says. “And what we learn can then be leveraged to help generate robust immune responses against a variety of infections and inflammatory diseases.”

Acharya says he appreciates the encouraging environment and the culture of innovation surrounding his work at the Fulton Schools.

“There is an active exchange of project strategies between faculties of vastly different areas of research here,” he says. “And this interdisciplinary focus has guided me to come up with some novel ideas.”

For example, his team has created a computer game to engage and inform undergraduate and graduate students about various aspects of metabolism and the immune system. Players of "Immunity Rage" choose different metabolites, inhibitors and enzymes to guide a vehicle along different metabolic pathways while learning about amino acid synthesis, fatty acid oxidation and more. They also tackle challenges like glycolysis hijacking by cancer cells that hinder the immune cell function.

Acharya also says he is grateful for the recognition of his work and financial support from the National Science Foundation.

“It truly helps me to do my part in advancing the mission of the Fulton Schools, and ASU in general, to integrate research and education in ways that yield meaningful societal benefit,” he says.