MCCTR grantee Kutcher receives NIH K-award

Published on Wednesday, February 19, 2020

By: Karen Bascom

Dr. Matthew Kutcher, assistant professor of trauma and critical care surgery, received a five-year NIH award, “Mitochondrial DNA in the Pathogenesis of Post-injury Coagulopathy,” in 2020. The grant explores underlying mechanisms of - and some potential therapies for - patients who become hypercoagulable during their recovery from injury, which puts them at risk for certain complications like deep vein thrombosis or pulmonary embolism. 

According to Dr. Joey Granger, Kutcher’s grant exemplifies the early successes of the National Institute of General Medical Sciences IDEA Program-supported Mississippi Center for Clinical and Translational Research.

“This is a major accomplishment for Matt as he is one of a few clinician scientists with NIH funding at UMMC,” Granger said. “He also represents a success for the MCCTR since the center supported his development as a new investigator and provided funds and salary support until he received his own NIH funding.”

Kutcher said the study originated from his clinical experience of taking care of injured patients.

“There have been tremendous advances in the surgical and ICU care of patients who are injured in the last 10 years,” Kutcher said. “Despite these advances in strategies to control bleeding, I think most trauma surgeons carry around the memories of certain patients who had bleeding that they just couldn’t stop.

“In some cases, we just needed to be faster . . . but in many cases, the problem we needed to fix isn’t with physics, it’s a problem with biology. We just don’t have a complete biological understanding of what makes some patients’ blood fail to clot normally when it should, or to become too prone to clot formation when it shouldn’t.”

He began working on the project as a research fellow during his general surgery residency training at San Francisco General Hospital.

“Since coming to UMMC, with the support of early funding from MCCTR, I’ve been able to start building our own trauma-focused surgical research laboratory to continue and expand this research.”

The study aims to understand whether the release of small DNA fragments into the bloodstream after major traumatic injury leads to abnormalities in blood clotting. It includes three arms:

• Researchers collect blood samples and follow outcomes in injured patients in whom clotting abnormalities are identified and different types of circulating DNA are measured.
• Researchers collect blood samples and information from healthy volunteers. Platelets are isolated from the blood samples to test the effects of exposure to DNA.
• An animal model of orthopaedic injury is used to test potential treatments for DNA-related clotting abnormalities that may one day be developed for use in humans.

“Usually, DNA belongs safely inside of our cells,” Kutcher said, “but when it ends up in the bloodstream, it can directly trigger clot formation and can bind to and activate cells like platelets and neutrophils. Since this circulating DNA can float freely around the body, it can lead to blood clot formation that isn't located at the site of the actual injury.

“Early after injury, we think this can inappropriately use up necessary blood clotting factors required for clot formation where it's actually needed. Later after injury, we think this can lead to abnormal blood clot formation, for example, in the legs or in the lungs.”

Kutcher said the MCCTR’s Investigator Development Program played an instrumental role in his successful NIH grant application.

“None of my work here would have been possible without the support of the program,” he said. “The early funding and protected research time allowed me the resources to design and implement the three major arms of the study. As many young investigators can attest to, early support in this work is critical.

“Using preliminary data gathered as part of MCCTR-funded work, I was able to obtain two other pilot grants that allowed us to expand the scope of our coagulation studies to focus specifically on circulating DNA and on platelet function. MCCTR's Investigator Development Program provides longitudinal funding support and mentorship for young investigators for the several years that it takes to build the infrastructure, develop the collaborative networks, generate and analyze the data, and submit the additional grants needed to transition towards independent funding.”  

While this first NIH award will support the study through 2025 in the amount of $162,800 annually, Kutcher has his scientific sights set for the long haul.

“My honest hope is that we can continue to write grants and find other sources of financial support to fund this study for as long as injured patients come here to UMMC for their trauma care,” he said. “There is always something we can learn to do better.”