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Lawrence David and collaborator Anthony Sung (Department of Medicine, Division of Hematologic Malignancies and Cellular Therapy) have been awarded a Stage 2 Damon Runyon-Rachleff Innovation Award. Their project, “Personalized prebiotics to optimize microbiota metabolism and improve transplant outcomes,” aims to tailor strategies to manipulate the microbiota through prebiotics patients take.

Patients being treated for leukemias, lymphomas and other blood cancers commonly receive bone marrow transplants as part of their treatment. However, about half of patients who receive a bone marrow transplant also contract graft vs. host disease and become very ill; a third of patients with graft-vs-host disease will die. Graft-vs-host disease happens when donor immune cells (graft) recognize patient cells (host) as foreign, leading to inflammation and tissue damage, and there’s reason to believe the microbiome may be a factor in contracting this disease.

When the microbiome gets altered after a transplant, it may send feedback that something is wrong in the body, which contributes to the inflammation. “If you can improve the microbiome after the transplant,” David said, “then you can potentially reduce the incidences of graft-vs-host disease.”

Prebiotics may be able to help. They are dietary ingredients that can stimulate the growth and maintenance of various beneficial bacteria that can help mitigate treatment complications associated with stem cell transplants used to treat blood cancers.

“Unlike probiotics, which are live bacteria that can translocate into the bloodstream and cause sepsis, prebiotics are likely safe for transplant patients,” Sung said. “At the same time, because prebiotics act on existing bacteria in the gut, their effects may vary depending on the composition of the patient’s microbiota.”

Since everyone has a unique microbiota, each patient may respond differently, so David and Sung are developing approaches to personalize prebiotic treatments for hematopoietic stem cell transplant patients based on their individual gut microbiota. They believe that by using this novel system, they will be able to predict the best prebiotic for a given patient, thereby manipulating their microbiota and improving cancer outcomes. Their project will test this strategy using patient samples in their artificial gut “bioreactor” as well as in mouse models. If successful, the next step will be clinical trials of personalized prebiotics.

The Damon Runyon-Rachleff Innovation Award funds cancer research by exceptionally creative thinkers with “high-risk/high-reward” ideas who lack sufficient preliminary data to obtain traditional funding. The awardees are selected through a highly competitive and rigorous process by a scientific committee comprised of leading cancer researchers who are innovators themselves.

David and Sung were two of five awardees to receive Stage 2 funding, which was granted to researchers who have shown significant progress during the first two years of the award. Their initial award was in January 2018.  

Story originally published January 28, 2020

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