New Funding Propels Research into Key Enzyme Involved in Inflammation
The study sets out to test a potential new pathway to treat osteoarthritis and other chronic inflammatory diseases
A newly funded study at the UC San Diego Department of Orthopaedic Surgery has set out to investigate a very important enzyme’s role in the human body’s inflammatory response.
Under Assistant Professor in Residence Elsa Sanchez-Lopez, PhD, and UC San Diego Assistant Professor of Pharmacology, Chemistry & Biochemistry Johannes Schöneberg, PhD, researchers are studying how the enzyme CMPK2 influences white blood cells’ energy demands in response to injury or infection, and how it helps trigger lasting inflammation.
The work, which will receive more than $3.4 million over five years through a major National Institutes of Health (NIH) grant, builds on previous research from the Sanchez-Lopez lab. Its findings could help inform the treatment of common chronic inflammatory conditions, including osteoarthritis.
Currently, researchers know that macrophages—a type of white blood cell—act as the body’s “first responders” following a tissue injury or infection. Once they arrive on site, these tiny defenders can change their own metabolism and energy demands to fit the crisis at hand.
In these early moments, macrophages often send out chemical “messengers” to attract other types of immune cells to fight the invader—usually bacteria or viruses—or repair damaged tissue after injury.
Previous collaborative research linked CMPK2 to macrophages’ ability to launch the body’s acute inflammatory response by activating key inflammatory mediators. Recent data from the Sanchez-Lopez lab suggest that CMPK2 also controls how macrophages shift their internal energy demand to sustain that response over time.
Now, the team’s goal is to identify the specific mechanisms and pathways CMPK2 controls to inform new clinical therapies for runaway inflammation.
“If we can therapeutically modulate the metabolic changes and the energy demands of macrophages, for instance by targeting CMPK2, then we can turn down the inflammatory response in the context of chronic inflammatory diseases,” said Sanchez-Lopez.
For many chronic inflammatory conditions, a discovery like this could shift the paradigm from easing a patient’s pain to treating their disease. The shift would allow healthcare professionals to focus on slowing or stopping a disease from destroying joints, as in the case of osteoarthritis, or preventing the body from rejecting joint replacements.
The researchers will collaborate with clinicians in the Department of Orthopaedic Surgery to collect human blood and tissue samples for study.
“Collaboration between clinicians and researchers is essential,” said Sanchez-Lopez. “The only way we answer human-relevant questions is when we work together to advance science and develop new treatments for patients.”
About the Grant
Research reported in this publication is supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R01AI192777. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.