Why do some people get sick while others feel fine?

June 3, 2021

Why do some people get sick while others feel fine?

Laura-Isobel McCall

NORMAN, OKLA. – The answer is something infectious disease experts are working to uncover. As COVID-19 revealed, the same pathogen can have widely varying outcomes in different people.

Laura-Isobel McCall, an assistant professor in the Department of Chemistry and Biochemistry in the University of Oklahoma’s College of Arts and Sciences, was selected as one of the 2021 Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Disease. This highly competitive PATH award provides $500,000 over a period of five years to facilitate multidisciplinary approaches to the study of human infectious diseases.

“OU is proud to have its faculty recognized by prestigious research awards such as the one given to Dr. McCall by the Burroughs Wellcome Fund,” said OU vice president for research and partnerships Tomás Díaz de la Rubia. “Her fundamental research is at the frontiers of her field and is helping advance our understanding of some of the most vexing questions in the field of infectious disease. Even at this early stage in her career, Dr. McCall is already having a significant impact on a very important field.”

McCall’s lab uses liquid chromatography mass spectrometry, 3-D metabolomics and data science tools to better understand why pathogens affect different parts of the body differently and why those differences also vary from person to person.

The PATH award is particularly exciting, McCall said, because it is a more holistic way to approach infectious disease research. Rather than focusing more specifically on the source of an infection, this award enables researchers to focus on the larger experience.

“One of the key rules that determine how bad a disease can be is the body part that is affected,” McCall said. “What we’re getting at is uncovering the fundamental rules that govern location of disease. The unique way we’re doing this is that rather than looking at the pathogen side of things, we’re looking at how each different organ in your body responds to infection on a chemical level.”

A plot of how the esophagus stays perturbed even after Trypanosoma cruzi parasite levels decrease

“I think it’s a new idea to focus on how the body responds to a pathogen, rather than focusing more directly on a pathogen itself,” she added. “That’s not saying that the pathogen doesn’t matter. It really matters what agent causes the infection, but then we need to bring all the parts together.”

McCall said this approach looks at the source of the problem – which parasite – then at the body’s immune response and how that contributes to damage in one part (or another) of the body, then drug treatment and recovery, and whether some body parts are naturally going to respond better to the infection – if they are going to go back to normal while others stay damaged even after treatment. In short, this research allows for a broader picture of infectious disease that makes room for the many variables that could influence outcomes and, spatially, how organs recover.

“For example, does the whole heart go back to normal? Does the tip of the heart stay perturbed? The spatiality and the focus on small chemicals, rather than proteins, is new and exciting” she said.

The PATH award is “game changing,” McCall said. “You need the resources from this award to make a big impact. This is something I strongly believe in, so even without the resources I would have kept trying toward this in small pieces over 15, 20 years that maybe would have assembled into the big picture. This award lets us do it all in the way it should be done to give us a comprehensive view.”

“It’s a monumental honor,” she added. “It’s a testament to the hard work the whole lab has put in for us to get the point to develop the idea and the preliminary data that helped conceptualize this bigger project.”

McCall, who also holds a position in OU’s Department of Biology and Microbiology in the College of Arts and Sciences, says her expertise blends chemistry/biochemistry and biology/microbiology, while also integrating experience in drug development, metabolomics and analytical chemistry. Likewise, the members of her lab cross multiple disciplines, including biochemistry, analytical chemistry, microbiology, anthropology and data science.