Robert Tower
University of Texas Southwestern Medical Center, TX·Microbiology & Immunology
After a severe injury to an arm or leg, inflammation at the wound is only part of the story. The body also changes how it makes blood and immune cells in the bone marrow, far from the wound.
- Fields
Microbiology & Immunology
Physiology
Medicine & Clinical Research
- Topics
itaconate
neutrophils
Acod1
- Grants
- 1 known grant, through Apr 2029
What they work on
- Identify the transcriptional and metabolic signals that switch on Acod1, the gene whose enzyme makes itaconate, specifically in mature neutrophils at the injury site, including the role of the damage sensor TLR9.
- Determine how shifts in glucose and glutamine use through glycolysis and oxidative phosphorylation enable injury-site neutrophils to produce the anti-inflammatory metabolite itaconate, using metabolomics and single-cell RNA sequencing.
- Map the trafficking of itaconate-laden neutrophils from the injured limb back to the bone marrow in a mouse polytrauma model of heterotopic ossification, abnormal bone formation in soft tissue.
- Test whether macrophages that engulf itaconate-laden neutrophils in the marrow lower their Il1b expression and thereby skew hematopoiesis, the production of blood and immune cells from stem cells.
More about the research
How the injury site sends that message has been unclear. The standard explanation is that signaling proteins called cytokines leak into the blood until enough accumulate for blood stem cells in the marrow to notice, a slow and insensitive mechanism. This project proposes a different route: neutrophils, short-lived first-responder immune cells, carry a chemical message out of the wound and deliver it back to the marrow.
Why it matters
Severe limb trauma triggers body-wide immune changes that affect healing and complications such as heterotopic ossification, abnormal bone growth in injured soft tissue. Showing that neutrophils ferry the anti-inflammatory metabolite itaconate from wound to bone marrow would identify a controllable link between a local injury and the systemic immune response, which could eventually point to ways to tune inflammation and blood cell production in trauma patients.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Benjamin Levi
University of Texas Southwestern Medical Center, TX·Medicine & Clinical Research
Map lymphatic vessels around skeletal and heterotopic bone after injury in mice, and test whether blocking VEGFR3-driven lymphatic growth worsens heterotopic ossification.
Laura Calvi
University of Rochester, NY·Medicine & Clinical Research
Test whether pre-leukemic mutant blood cells form clones and progress to myelodysplastic syndromes more readily in an aged marrow environment, by transplanting mouse models of clonal hematopoiesis into young versus aged recipient mice.
Katrin I. Andreasson
Stanford University, CA·Neuroscience
Test whether reprogramming energy metabolism in aging microglia and blood macrophages, by blocking inflammatory PGE2 signaling, can prevent or reverse cognitive decline in aging and Alzheimer's model mice.
The school
University of Texas Southwestern Medical Center: 40 labs on PI Pages, $869M a year on research, 86 research doctorates a year.
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