Competition winners for our grant program in conjunction with Alex's Lemonade Stand Foundation have been announced.
Following is a brief introduction to the principal investigator and the primary topic of research for our first grant cycle. We are thrilled to have such a strong, diverse selection of renown researchers as partners.
Dr. Ravi Majeti, Stanford University, ‘Characterization of Pre-Leukemia Associated with Familial RUNX1 Mutations’. Dr. Majeti and his team propose to investigate the disease pathogenesis and pre-leukemia by determining the effects of familial RUNX1 mutations on hematopoietic stem and progenitor cells using CRISPR methods and a mouse host model. Additionally, they aim to determine the contributions of familial RUNX1 mutations in HSPCs and the bone marrow microenvironment to aberrant pre-leukemic hematopoiesis.
Dr. Alan B. Cantor, Boston Children’s Hospital, ‘Pharmacologic Enhancement of Residual Wild Type RUNX1 Protein Activity in FPD/AML’. Dr. Cantor will investigate whether enhancing the residual wild type RUNX1 protein by pharmacologic means is able to reduce the chances of progression to MDS/ leukemia as well as improve the platelet function of the disorder. The hope is to understand RUNX1 regulation in order to develop therapies for RUNX1-related hematologic malignancies. By using pluripotent (iPSC) cell lines from FPD/AML patients and an in vivo mouse model, the research aims to establish the extent to which SFK inhibitors enhance total RUNX1 activity as well as to establish a high throughput assay for RUNX1 transcriptional activity and screen about 100,000 compounds for additional enhancers.
Dr. Eirini Papapetrou, Icahn School of Medicine at Mount Sinai, ‘Identifying Therapeutic Targets to Prevent Progression of Familial RUNX1 Disorder to AML using Novel iPSC Models’. Papapetrou’s lab aims to develop an iPSC-based model of progression of familial RUNX1 disorder with the goal of identifying therapeutic targets to prevent leukemia progression.
Dr. Marshall S. Horwitz, University of Washington, ‘Restoring RUNX1 Levels in FPD/AML’. Dr. Horwitz’s research aims to inhibit the degradation of the wild-type RUNX1 protein through the ubiquitin-proteasome pathway by evaluating drugs currently in use or undergoing clinical trials in other forms of cancer. Additionally, his research will attempt to boost RUNX1 expression to reset its auto-regulatory circuit. Studies will be performed using patient-derived iPSC.
Dr. Leonard I. Zon, Boston Children’s Hospital, ‘Modeling RUNX1-associated Clonal Hematopoietic Disorders in Zebrafish’. Dr. Zon will use his ‘famous’ zebrafish program to model RUNX1 FPD/AML to study and understand the combination of secondary mutations to understand disease pathogenesis. This would allow for early recognition in order to reverse abnormally mutated clonal expansion and restore normal hematopoiesis.