The role of brain-bone marrow-GUT interaction following major trauma
Active Project Grant Awarded Last action
- Award ID
- R35GM152216
- Recipient
-
University Of Florida UEI NNFQH1JAPEP3
- Awarding agency
-
National Institute of General Medical Sciences
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,830,000
Award facts
- Assistance listing
- 93.859 Biomedical Research and Research Training
- Completion date 43% complete
- Place of performance
- Gainesville, FL 32611, USA
Award details come from USAspending.gov.
Description
- Abstract
- Trauma remains the leading cause of death among people younger than 46 years of age and is the leading cause of years of potential life lost among those younger than 65. With more lives saved, trauma morbidity has increased, which has consequently revealed a lack of understanding of the impact of trauma survivorship on the patients' quality of life and long-term recovery. Severe injury when followed by chronic critical illness leads to persistent anemia, and the use of blood transfusions is associated with a linear increase in infectious complications. These conditions are due to prolonged bone marrow dysfunction associated with an exaggerated catecholamine response, chronic stress, and systemic inflammation. The principal investigator (PI) has demonstrated significant productivity over the last decade, especially in the last five years, in this research field. The PI's laboratory has conducted human and rodent research to establish that there are unique bone marrow transcriptomic differences related to inflammation, the innate immune response, and known inhibitors of erythropoiesis following trauma. The laboratory has also discovered that chronic stress after trauma contributes to persistent anemia with impaired iron and erythropoietin function along with the prolonged loss of hematopoietic stem progenitor cells (hspc) from the bone marrow. Chronic stress after trauma also induces an altered microbiome with decreased alpha and beta diversity and changes in microbial composition leading to a persistent 'pathobiome'. All of these factors influence outcomes. We hypothesize that there is a unifying interaction between stress, inflammation, and the microbiome and this has an overall role in the regulation of hspc and erythroid progenitor cell fate and function following trauma and critical illness. Therefore, the overarching goal for this application is to build upon this foundation and expand our understanding of hspc fate and function following trauma, including examining interventions aimed at reducing stress/inflammation and restoring the microbiome, thus, improving long-term outcomes. Severely injured patients with chronic critical illness at risk of long-term morbidity as well as our novel preclinical rodent model of multicompartmental trauma and chronic stress will be employed. We intend: (1) to directly link changes in hspc and erythroid progenitor cell fate and function with changes in the microbiota by examining specific mechanisms, including how stress-induced changes following trauma create a pathobiome that maintains altered erythroid progenitor function. With these studies, we will (2) explore the unique interplay of the microbiome, the stress response, and hspcs and erythroid progenitor cell fate in different cohorts of trauma, evaluating both age and SEX; and (3) consider possible interventions that restore the microbiome and/or reduce chronic stress/inflammation which reestablishes hspc homeostasis to improve bone marrow function and long-term outcomes. Focusing on longitudinal interactions between the dysregulated stress response, the pathobiome, and hspc fate is a novel, under-explored area of research that could improve the long-term management of severe trauma.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $457,500 | |
| Amendment | $457,500 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $457,500 | |
| Original award | $457,500 |
Quick answers
Who received award R35GM152216?
R35GM152216 was awarded to University Of Florida by National Institute of General Medical Sciences (National Institutes of Health) on September 10, 2024.
How much is award R35GM152216 worth?
$1,830,000 has been obligated on R35GM152216.
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