Research Projects Funded

Following are competition winners for our grant in conjunction with the Leukemia and Lymphoma Society (LLS) and Alex's Lemonade Stand Foundation. Below 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.

RUNX1-LLS (Leukemia and Lymphoma Society) 2017 Grant Awardees  

Dr. Guy Sauvageau, University of Montreal, Canada, ‘RUNX1 mutations that confer exquisite sensitivity to glucocorticoids’. Dr. Sauvageau discovered that a class of steroid hormones called glucocorticoids selectively inhibits the growth of acute myeloid leukemia (AML) cells containing RUNX1 mutations in cell culture. He plans to determine how glucocorticoids inhibit the growth of RUNX1 mutant AML cells, and to test the ability of glucocorticoids to inhibit AML in a mouse model. 

Dr. Benjamin Ebert, Harvard Medical School, USA, ‘Interaction of RUNX1 and the cohesin complex in megakaryocyte development and myeloid disease’. Dr. Ebert will study the cooperation between mutations in RUNX1 and in a gene encoding a member of the cohesin complex, STAG2. He plans to generate a mouse model for the combined RUNX1 and STAG2 mutations and study hematopoiesis and leukemia progression. He will also evaluate inhibitors of CDK8, a member of the transcriptional mediator complex, for their activity and mechanism of action in the context of RUNX1 and/or STAG2 mutations. 

Dr. Stephen Nimer, University of Miami - Miller School of Medicine, USA, ‘Epigenetic-modifying enzymes in FPD/AML’. Dr. Nimer will evaluate the ability of inhibitors or activators of epigenetic gene regulation to promote the differentiation, or inhibit the self-renewal, proliferation, and survival of RUNX1 mutant hematopoietic cells derived from cultures of human-induced pluripotent stem cells (iPSCs). He will also generate a mouse model with combined mutations in RUNX1 and in a gene called ASXL1, which have been found to co-occur in a subset of FPD/AML patients with AML, and test the activity of inhibitors or activators of epigenetic gene regulation in this model. 

RUNX1-ALSF (Alex's Lemonade Stand Foundation) 2016 Grant Awardees

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.