Establishing Biomarkers of Stem Cell Fitness to Improve HSC Transplants for Pediatric Cancer Patients
Hematopoietic stem cell (HSC) transplant is an essential component of cancer therapy for pediatric patients with aggressive leukemias that have relapsed or are at high risk of relapse. Donor HSCs regenerate blood and immune cells in the patient, and if the function of these donor cells is impaired, the recovery process after HSC transplant is delayed. The number of HSCs received from the donor is traditionally used to predict the success of the HSC transplant, but cell dose is not always the best predictor of transplant success. HSCs require careful regulation of their protein health and a disruption in this balance leads to accumulation of improperly made or misfolded proteins and impairment of HSC fitness and function. Through the proposed project, I aim to determine the biological factors that promote optimal function of HSCs during transplant and will investigate the use of proteostasis as a biomarker for identifying grafts with poor quality HSCs. By identifying HSCs with disrupted proteostasis, we could select and transplant more fit HSCs to significantly improve the recovery process and quality of life for children with leukemias who require HSC transplant.
Project Goal:
Through the proposed project, I aim to determine the biological factors that promote optimal function of HSCs during stem cell transplant. I will investigate the use of stem cell protein health as a biomarker for identifying donor stem cells with poor quality HSCs. By identifying HSCs with poor protein health, we could select and transplant more fit HSCs to significantly improve the recovery process and quality of life for children with leukemias who require HSC transplant as part of their treatment.
