The Regents of the University of Michigan C.S. Mott Children's Hospital Archives

2019

Young Investigator

Daniel Peltier

Anne Arbor, MI

Executive Summary: Hematopoietic stem cell transplantation (HSCT) is required to cure many childhood cancers; however, it is often complicated by severe side effects. The new immune system that children receive after HSCT is responsible for these severe side effects as well as the curative cancer-fighting effect. Unfortunately, we do not know how to precisely fine tune this new immune system to make HSCT safer and more effective. Our work seeks to further understand how a component of this new immune system is controlled by a recently identified class of genes called long non-coding RNA’s (lncRNA). These lncRNA genes do not make proteins like classic genes, but instead regulate the production and function of proteins made by classical genes. Previous work from our lab identified a novel lncRNA, Linc00402, that is turned on in patients and lab models of HSCT. Linc00402 is unique to a specific component of the immune system, which may make it a promising and specific target for improving HSCT. However, it is not known if or how Linc00402 influences the new immune system after HSCT. Therefore, I seek to further understand how Linc0042 affects the new immune system following HSCT. Specifically, I propose to: 1) investigate the effect of Linc00402 on both the undesirable side effects and desirable anti-cancer effect of the new immune system after HSCT in animal models, and 2) determine the influence of Linc00402 on precise immune functions important for immune-system related effects after HSCT. The results of these studies may suggest ways of developing medicines to improve HSCT for pediatric patients with high-risk cancers.

Goals:
• Determine if Linc00402 impacts undesirable side effects and/or the desirable anti-cancer effect of the new immune system after experimental HSCT.
• Determine the effect of Linc00402 on precise features of immune function, which will clarify how Linc00402 regulates the immune system.