UF receives $9 million renewal for chronic critical illness research

The University of Florida’s Sepsis and Critical Illness Research Center has received a renewed National Institutes of Health grant worth about $9 million over six years, research.med.ufl.edu reports. The funding will support the next stage of a long-term effort to understand why some patients recover from life-threatening illness while others remain sick for months or longer.

The award comes from the NIH’s National Institute of General Medical Sciences through its RM1 Collaborative Program Grant for Multidisciplinary Teams. It supports the second phase of a planned 10-year research programme examining chronic critical illness, a condition in which survivors of sepsis, major trauma or severe burns experience an extended decline in physical and biological function.

The centre’s work is aimed at developing precision medicine approaches that could help doctors identify patients’ individual patterns of immune dysfunction and match them with more suitable treatments.

Why recovery can remain out of reach

Improved hospital care has helped reduce the number of people who die during the acute phase of sepsis. But surviving the initial crisis does not always mean returning to health. Some patients develop chronic critical illness, which may bring lasting disability and raise the risk of death during the year after leaving hospital.

SCIRC researchers are studying whether a damaging form of immune memory helps explain this prolonged illness. Their central theory focuses on maladaptive trained immunity, or mTRIM. The process involves myeloid cells, a large category of white blood cells that responds early to infection and tissue damage.

Immune memory usually helps the body react efficiently when it encounters a threat again. In mTRIM, however, the cells may remain in an abnormal condition after the original illness has passed. That state can sustain inflammation while impairing other parts of the immune response. The researchers say these changes include lasting alterations in gene activity and in the way cells use their mitochondria, the structures responsible for producing cellular energy.

The centre is also examining myeloid-derived suppressor cells, known as MDSCs. These cells were first identified in people with cancer. SCIRC investigators later found that they can build up in some survivors of sepsis, particularly those who go on to have poor outcomes.

Four strands of the renewed programme

The new grant builds on four years of work supported by the centre’s first RM1 award, which began in 2021. That earlier research showed that immune abnormalities and MDSC behaviour were not uniform: they varied between patients and according to the infection involved.

The renewed programme has four main areas of investigation. Researchers will study how immune-cell genes are regulated, how the cells produce and use energy, and how the relevant cell populations develop from stem cells in bone marrow. The team will also work on tools that could assess patients’ condition in real time and investigate treatments designed for particular immune profiles.

The treatment effort will include immunotherapeutics and the use of artificial intelligence to help identify potential medicines. The aim is to move beyond treating critically ill patients as a single group and instead establish quicker ways to recognise distinct biological patterns.

The project brings together researchers from five UF colleges. Its four principal investigators are Philip A. Efron, director of SCIRC and the grant’s contact principal investigator; Michael Kladde, director of the Center for Epigenetics; Robert Maile, associate professor of surgery and SCIRC co-director; and Clayton Mathews, chair of infectious diseases and immunology in UF’s College of Veterinary Medicine.

A possible route towards clinical trials

The centre hopes the renewed research will produce both clearer patient classifications and practical ideas for targeted therapy. Its longer-term ambition is to discuss precision-medicine clinical trials in a future programme-grant application.

That prospect depends on translating laboratory findings into methods that can be used during or soon after intensive care. Identifying which immune pathways are disrupted, how severely they are affected and which treatment might help could give clinicians a more detailed basis for decisions after a patient survives the initial emergency.

SCIRC is also using September to encourage public awareness of sepsis. The centre plans campus and community events at UF Health during the month and is urging people to learn the condition’s warning signs. Its researchers emphasise that sepsis can affect families as readily as other major medical emergencies, including stroke and heart attack.

The NIH support is formally awarded under RM1GM139690. The grant notice states that the work is funded by the National Institute of General Medical Sciences and that responsibility for the research rests with its authors, rather than representing the official position of the NIH.