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Crossing New Horizons in Immune Research

By Randolph Fillmore

When Martin Trapecar, Ph.D., an assistant professor in the Division of Endocrinology, Diabetes and Metabolism at the Johns Hopkins University School of Medicine, established The Laboratory of Human Biomimetics at Johns Hopkins All Children’s Hospital in 2021, his first task was to build a dedicated research team to explore the fundamental origins of immune-metabolic diseases.  

Now in place, that team is focused on unraveling the causes behind inflammatory bowel disease (IBD), a term used to describe disorders that involve chronic inflammation of the digestive tract and include ulcerative colitis and Crohn's disease, both of which are characterized by inflammation of the lining of the digestive tract and its deeper layers. 

Because IBD is increasingly affecting children and adolescents, Trapecar said there is a strong motivation at Johns Hopkins All Children’s for solving some of the biological mysteries behind IBD and its influence on overall health beyond the intestine.  

“Many patients develop IBD in childhood or early adolescence, which also significantly affects their well-being into adulthood.  There is a strong and urgent motivation to discover why this is happening and, hopefully, find better ways to treat or prevent it,” Trapecar explains.  

A $2 million NIH Grant has ‘Opened Doors’ 

Help in reaching these goals recently arrived when Trapecar and his colleagues received a competitive “Maximizing Investigator’s Research Award” (MIRA) to help facilitate their research. The five-year, $2 million federal grant came from the National Institutes of Health’s (NIH) National Institute of General Medical Sciences (NIGMS), which offers grants to promising early-stage investigators (ESI) conducting research on basic biological processes.  

While the full title of the grant — NIH NIGMS ESI MIRA Grant — may sound like “alphabet soup,” the important funding will help them continue to build advanced models of human multi-organ physiology and organ-to-organ “cross-talk.” 

Organ ‘Cross-talk’ and the ‘Human on a Chip’ Concept 

For some time, to look for possible pathways related to the development of IBD and other inflammatory diseases, Trapecar has been investigating the “gut-liver axis” as it interacts with the immune system under both disease and normal conditions.  

To aid in this effort, researchers in the Trapecar lab create models of diseases using a tool called a “human on a chip.” In more technical terms, the technology is called a “microphysiological system” (MPS). Trapecar says MPSs are built using donated human tissue and cells to recreate, in miniature, aspects of complex human biology that are influenced by inter-tissue communication. This technique allows the researchers to re-engineer and apply simplistic versions of disease under highly controlled conditions, then examine how tissues and cells react.  

“The MPS technology offers insight into how disruption in the cross-talk between tissues and the immune system can lead to the early emergence of autoimmune disease, such as inflammatory bowel disease and degenerative disorders,” Trapecar explains. “When we recreate disease conditions, we can better understand biology unique to humans as well as stresses and environmental conditions that also can affect tissues and cells.” 

MPSs have the potential to revolutionize preclinical research that historically has relied on studies conducted using animal models. 

Read more:  Read the full story by Randy Fillmore

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