The renewed RM1 grant will focus on chronic critical illness in survivors of sepsis, trauma and severe burns.
By Manny Rea
The UF Sepsis and Critical Illness Research Center (SCIRC) grant to investigate chronic critical illness has been renewed by the National Institutes of Health (NIH), totaling about $9 million over six years. The renewal will aid investigations into why some critically ill patients recover — and why others don’t.
The award, issued through the NIH’s National Institute of General Medical Sciences under the RM1 Collaborative Program Grant for Multidisciplinary Teams mechanism, will fund the second phase of a planned decade-long research program focused on chronic critical illness (CCI), prolonged physiological decline affecting survivors of sepsis, trauma and severe burns.
“The intent of the grant is to delineate precision medicine,” Philip A. Efron, M.D., said, the Cracchiolo Family Professor of Surgery, director of SCIRC and the grant’s contact principal investigator.
While advances in sepsis care have reduced acute hospital mortality, many survivors go on to develop chronic critical illness (CCI), which can lead to prolonged disability and an increased risk of death within a year of hospital discharge.
Central to the team’s hypothesis is maladaptive trained immunity, or mTRIM, a dysfunctional form of immune memory that can persist after a patient survives a severe illness. mTRIM involves myeloid cells, a broad group of white blood cells that serves as an early line of defense against infection and injury.
Normally, these cells retain a kind of memory of past threats, allowing them to respond differently to future challenges. But in mTRIM, that memory may become harmful: myeloid cells remain locked in an abnormal state that contributes to persistent inflammation while also weakening other immune responses long after the initial illness.
“Myeloid cells also have memory,” Efron said. “You can get stuck because of mTRIM. The cell is stuck in a maladaptive state. It doesn’t get better, and it has these long-term changes that occur in its gene expression as well as its mitochondrial response.”
Also, key are myeloid-derived suppressor cells (MDSCs) first identified in cancer patients and found by SCIRC researchers to accumulate in sepsis survivors with poor outcomes.
Building on four years of findings from the center’s first RM1 award, funded in 2021, which revealed that immune dysfunction and MDSCs in critically ill patients differed depending on the individual and infection involved. The renewed grant pursues four specific aims: investigating immune-cell gene regulation, energy use, origins in bone marrow stem cells, and real-time clinical tools as well as patient-focused Immunotherapeutics, including AI-assisted drug discovery.
The project draws expertise from five UF colleges and is led by four principal investigators: Efron; Michael Kladde, Ph.D., professor and director of the Center for Epigenetics; Robert Maile, Ph.D., associate professor of surgery and co-director of SCIRC; and Clayton Mathews, Ph.D., chair of infectious diseases and immunology in the College of Veterinary Medicine. “This work is possible because of the extraordinary expertise and commitment of our principal investigators, co-investigators, collaborators, and the dedicated SCIRC staff who bring this highly collaborative research program to life,” Efron said.
“I think we can make enough progress to not only better define patients rapidly, but to have some ideas on how to treat them specifically,” Efron said. “It’s my hope that when we go for our next program grant, we will be able to start talking about clinical trials that involve precision medicine for these ICU patients.”
September is Sepsis Awareness Month
SCIRC is urging the public to learn the signs of sepsis this September. “Sepsis is just as frequent and just as likely to hurt people’s relatives as stroke or heart attacks,” Efron said. “There are a lot of researchers who really want to make a dent in sepsis and help their loved ones come home and get back to normal.”
SCIRC will host campus and community events throughout the month at UF Health. For more information, visit https://scirc.med.ufl.edu/2026/09/03/september-is-sepsis-awareness-month-join-scirc-in-raising-awareness/
“Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under Award Number RM1GM139690. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”