New Insights into Immune Health

This article first appeared on UO's Phil and Penny Knight Campus for Accelerating Scientific Research website on July 11.

With funding from the Department of Defense, Knight Campus researchers are using data-enabled biotechnologies to identify at-risk patients and deliver life-changing precision therapies.

Recent advances in high-throughput biochemical assays — technologies that can measure thousands of compounds in a biological specimen — have enabled unprecedented insight into a patient’s immune health. Now, researchers believe these tools could help orthopaedic surgeons provide better treatment to victims of traumatic limb injury — a leading cause of permanent disability in both military service members and civilians. That’s the goal of trauma immunology research funded by a recent $2 million U.S. Department of Defense grant, involving researchers in the Guldberg Lab at the Phil and Penny Knight Campus for Accelerating Scientific Impact.

The focus of the research is nonhealing bone fractures, known as bone nonunions, which affect hundreds of thousands of Americans each year. It can take months to diagnose a nonunion by current methods, which is often too late to save the patient’s limb, resulting in amputation or permanent loss of mobility.

Scientists and clinicians have known for decades that trauma can cause an imbalance in the patient’s immune system. Enabled by new technologies — such as high-throughput proteomics, which can simultaneously measure thousands of proteins, and flow cytometry, which can analyze multiple types of cells in the blood — researchers at the University of Oregon and collaborators are studying the immune response to traumatic injuries in greater detail than previously possible. They are accumulating evidence that immune status may influence bone healing and developing tools to predict nonunion far earlier than current methods like x-ray allow.

“We have integrated these technological advancements with machine learning data analytics to show in preclinical models that we can predict trauma outcomes,” said Robert Guldberg, a principal investigator on the grant and vice president and Robert and Leona DeArmond Executive Director of the Knight Campus. “We are thrilled to now have DOD support to test whether these results can be translated to human trauma patients.”

The team now aims to extend their previous research into the clinic to study patients with severe tibia fractures. They hope to develop a powerful new diagnostic tool that can identify at-risk patients early in the treatment course and allow clinicians to provide more customized care. Further, the same biomarkers that predict nonunion may serve as targets for new drugs that seek to correct an imbalance in the immune system before it is too late.

“By the time a patient receives a diagnosis of nonunion, they have already endured months of pain, and will need revision procedures that cause additional suffering and are often unsuccessful,” said Kelly Leguineche, research engineer in the Guldberg Lab. “Our hope is this project will both enable earlier intervention and lead to new targets for future therapies, increasing the chances that patients will regain use of their limbs and have a higher quality of life.”

Sen. Jeff Merkley was instrumental in advancing appropriations funding for trauma immunology research. Prior to 2022, no such program existed to fund efforts to enhance survivability of patients and return them to function following severe injury. With support from now-retired U.S. Rep. Peter DeFazio, Merkley led the push to fund research in this area. In FY2022, Congress added $5 million in funding to address trauma immunology, specifically, and that number was increased to $10 million in FY2023. The Trauma Immunology Research Award (TIRA) now supports basic and applied research and early-stage development of material and knowledge products to address critical gaps in the understanding of immune system, immune response, immune function, and other associated host responses in combat injuries.

“Groundbreaking innovation today — including what’s happening at the University of Oregon’s Knight Campus — holds the potential to transform the way patients survive and heal after traumatic injuries,” said Sen. Merkley, who helped fund this initiative as a member of the Senate Appropriations Committee. “Not only will this federal funding I helped secure expand the understanding of traumatic injuries and treatments, but it will also better support the University of Oregon’s Knight Campus faculty’s excellent work to advance trauma research and develop treatments for helping Oregonians recovering from traumatic injuries. I’ll keep fighting to invest in important research initiatives like this, which improve the health and lives of Oregonians across the state.”

Sen. Ron Wyden, a longtime advocate for federal research funding, joined with Merkley in asking colleagues to support the research.

“This federal investment in world-class research at the University of Oregon’s Knight Campus will open up new areas of inquiry that generate solutions to help patients enjoy a better quality of life,” Wyden said. “Biosciences play a huge role in Oregon’s economy. And I’m gratified my alma mater once again is delivering on its promise for innovation that accelerates the benefits top-notch science can provide in our state and nationwide.”

Additional investigators on the grant include Drs. Todd McKinley and Roman Natoli, both professors at Indiana University School of Medicine, and Dr. Philipp Leucht, associate professor of orthopaedic surgery and cell biology at the New York University Grossman School of Medicine.

The UO is continuing to advocate for additional trauma immunology research with support from the Oregon delegation and the Coalition for the Advancement of Research and Innovation in Trauma (CARIT). Along with ongoing leadership from Senator Merkley, U.S. Rep. Val Hoyle submitted a dear colleague letter, signed by a half-dozen members of Congress, to the Defense Subcommittee of the U.S. House Committee on Appropriations requesting $20 million in funding for trauma immunology research in FY2024.

“By directing funding towards this vital field of research, we can tangibly support innovative treatments that will lead to better care, and better outcomes from traumatic injury,” said Rep Hoyle. “That’s why I am leading the effort in the U.S. House to support the University of Oregon’s promising research. I’m proud to help carry the torch to advance and sustain funding for this important initiative happening in our home state.”

Guldberg expressed gratitude to members of the Oregon congressional delegation, along with CARIT and UO’s Government and Community Relations team for their support helping to convince the DOD to identify trauma immunology research as a funding priority.

“The opportunity to conduct this multi-site clinical study after several years of lab work is very exciting and was only made possible by a real collaborative effort,” Guldberg said.

Guldberg says data-enabled biotechnologies like those to be used for the study are revolutionizing the ability to identify at-risk patients and deliver precision therapies. Several Knight Campus research labs are using similar approaches with the potential to have impact on a broad range of clinical applications. For more information, visit the Knight Campus website.