Project Grant R01HL181083

The National Heart, Lung, and Blood Institute awarded the University of Texas at Dallas $641,538 on August 15, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837, Assistance Listing R01HL181083) to investigate gut microbiome targets for sickle cell disease pain management.

The research addresses chronic pain in individuals with sickle cell disease, a leading complication that persists despite advances in disease-modifying and curative therapies and is often managed with opioids despite their long-term adverse effects and incomplete efficacy. Preliminary findings using the Townes transgenic mouse model of sickle cell disease demonstrated that the gut microbiota composition differs between sickle cell disease and healthy mice, and that fecal microbiota transplant from healthy control mice temporarily reversed chronic pain measures in sickle cell disease mice. Reciprocally, fecal microbiota transplant from sickle cell disease mice induced persistent pain in wildtype control animals. The award funds investigation of how standard-of-care penicillin prophylaxis—prescribed daily to infants diagnosed with sickle cell disease for the first six years of life—alters the gut microbiota and chronic pain development. Preliminary data indicate that early-life penicillin treatment exacerbates chronic pain-like behaviors in sickle cell disease mice. The project will examine mechanisms through which prophylactic penicillin treatment exacerbates chronic pain and test novel therapeutics targeting each identified mechanism.

Performance of work occurs in Richardson, Texas. The period of performance runs from August 15, 2026, through May 31, 2031.