NC rivals bond over their kindergarten-bound daughters and end up transforming the field of respiratory disease biology

Like a certain rivalry familiar to most everyone on campus, the competition between Duke University and the University of North Carolina runs deep. Though a work partnership – let alone a friendship – seemed unlikely when they met in 2017, former North Carolinians Michael Johnson and Julie Ledford found common ground through their daughters and their love for science.

Both members of the BIO5 Institute, Johnson, assistant professor of immunobiology, and Ledford, associate professor of cellular and molecular medicine, teamed up to determine the mechanistic role for a biomarker of obstructive lung diseases. The collaboration between Johnson – who earned a Bachelor of Arts in music from Duke – and Ledford – who received her doctorate in genetics and molecular biology from UNC – has led to a $2.5 million grant from the National Institutes of Health, and the team recently published field-shifting findings in the American Journal of Respiratory and Critical Care Medicine.

Mentorship, kindergarten and collaboration

The pair met through the College of Medicine's Faculty Fellows Mentoring Program. Spearheaded by the college's Office of Diversity, Equity and Inclusion. The initiative supports new faculty members from  underrepresented backgrounds and assigns them to mentors, who offer guidance on topics including promotion and tenure, laboratory leadership and managing conflict.

During a group outing to a local pizzeria, the two realized their daughters would be attending the same kindergarten later that year. Since they'd likely be seeing a lot of each other in the future, the Tar Heel and Blue Devil decided to put their institutional rivalry aside and meet for coffee.

"We didn't immediately know we were going to work together because we were from rival institutions. The Duke-UNC basketball rivalry is a very big deal, so we immediately thought there could be friction," joked Ledford, who is also an associate professor of clinical translational sciences and medicine.

While sipping coffee and talking about their children, the conversation shifted to their research. Ledford, a respiratory disease scientist who joined the University in 2015, told Johnson about a problem she was having with a project.

Based on the work of Fernando Martinez, director of the Asthma and Airway Disease Research Center, and Stefano Guerra, professor of medicine, Ledford knew that a protein produced in the lung – CC16 – served as a critical biomarker for obstructive lung diseases like asthma and chronic obstructive pulmonary disease. Higher levels of CC16 in the blood have been associated with protection from both the inception and progression of these respiratory diseases, but it was unknown exactly how the presence of a lung protein in the blood mediated disease.

Ledford wanted to push the field in a new direction by determining the mechanism behind this biomarker. But she needed outside expertise to determine with which proteins the biomarker might be interacting.

Johnson, who is trained in protein biochemistry and began at the University in 2016, asked Ledford to email him more details about the project.

"I really like understanding how proteins work," Johnson said. "CC16 was the perfect bite of a protein to be able to look at and say, ‘I wonder what this thing does.'"

As a testament to his collaborative spirit and enthusiasm about the project, Johnson called Ledford within an hour of receiving her email.

"I almost fell off my chair," Ledford recalled.

In that moment, their scientific partnership was born.

It takes a village

Since there were countless potential partners for CC16, both in the lung and blood, Johnson knew traditional techniques were out of the question. After examining the sequence of amino acids – the basic building blocks of protein, Johnson was amazed to find that a particular three-amino acid sequence he studied in graduate school was conserved in CC16 across several species.

This clustering of protein building blocks was known to be an integrin binding motif. More simply, just those three amino acids enable CC16 to bind to special receptors (integrins) that enable cells to attach to each other and to the foundation (extracellular matrix) upon which they sit in our tissues.

To better investigate the relationship between CC16 and integrins, Johnson and Ledford recruited several other BIO5 members to help: Francesca Polverino, associate professor of medicine and COPD physician-scientist; Casey Romanoski, assistant professor of cellular and molecular medicine and vasculature biology specialist; Monica Kraft, deputy director of the Asthma and Airway Disease Research Center and an expert in the role of infection in asthma; and Anne Cress, senior associate dean of academic faculty and basic science research in the College of Medicine – Tucson and integrin expert.

Through their teamwork, the group's members learned the conserved sequence of amino acids facilitated cell binding to VLA-4, an integrin involved in the recruitment of white blood cells. By modifying the sequence of CC16 using recombinant DNA technology, Johnson produced a mutant protein unable to bind the integrin.

After more investigation, Johnson and Ledford found that loss of the binding site impaired the function of CC16 in lung infection and inflammation.

Since paving this new direction for the field of obstructive respiratory disease research, the team is hopeful the work will lay the foundation for therapeutics to help prevent and mediate lung diseases.

An alliance for years to come

The former North Carolina rivals don't plan to end their collaboration anytime soon. By combining their expertise and techniques, they aspire to determine the precise location or locations of CC16-VLA-4 interactions, as well as how the protein can mediate the clearance of bacteria from the lung.

At the end of the day, Johnson and Ledford aren't just grateful for their scientific partnership – they are thankful for their unlikely friendship, which extends to their families.

"A lot of people are involved in scientific collaborations; you get to choose who you do collaborations with. But I'm very excited when I get to do collaborations with my friends," Johnson said.

"It's really nice to have these types of relationships with people because it illustrates why we do science and who the science impacts. If we're not having fun doing it, if we're not forming relationships and fellowship, then it would be a really boring and awful field," he added.

"The fact that we can sit down, be able to break bread together, and then also talk about science," he said, "it's just a really good feeling, and I'm lucky that I have the opportunity to have that."

A version of this article first appeared on the BIO5 website.