Grant: 1352-18 | Career Development Program (CDP):
Location:New York University School of Medicine, Boston, Massachusetts 02241-415026
Project Title: MicroRNA Regulation Of Leukemia Stem CellsProject Summary:
Acute myeloid leukemia (AML) is composed of two populations of cells with differing characteristics. The bulk population directly gives rise to the disease symptoms. The second population is very small and is composed of leukemia stem cells (LSCs), whose role is to initiate disease and generate the AML bulk population. These self-renewing LSCs are therapy resistant and mediate disease relapse; therefore, it is critical to understand the mechanisms that regulate LSCs in order to develop strategies designed with the intent to cure.
Grant: 6551-18 | Translational Research Program (TRP):
Location:The Board of Regents of the University of Wisconsin System, Madison, Wisconsin 53715-1218
Project Title: Matrix Remodeling In The Myeloma Niche: Implications For Minimal Residual Disease And ImmunotherapyProject Summary:
Despite a revolution in the way we treat myeloma in the last 10-15 years, the disease remains incurable for the vast majority of patients. We have devised powerful novel agents and strategies that kill myeloma cells efficiently, yet not at 100%. Some residual cells remain even after the best of treatments and act as the “seed” from which the disease relapses and ultimately claims human lives. In the last 4-5 years, we have become much better at measuring this “minimal residual disease”. Ultimately however, we should not only recognize and size the enemy, we should eliminate it.
Grant: 6528-18 | Translational Research Program (TRP):
Location:Board of Trustees of the Leland Stanford Junior University, San Francisco, California 94144-4253
Project Title: Identifying Relapse Associated Populations At Diagnosis In LeukemiaProject Summary:
Despite high rates of initial response to frontline treatment in many human cancers, mortality largely results from relapse or metastasis. Diverse clinical outcomes occur because all cells within a given tumor do not possess the same behavior or response to therapy. Although there is debate as to whether resistant populations of cancer cells are present at the time of initial diagnosis or whether these traits develop under the pressure of therapy, many studies have suggested that it is the former. Remission, by definition, is the reduction of cancer cells to undetectable levels.
Grant: 3371-18 | Career Development Program (CDP):
Location:The University of Chicago, Chicago, Illinois 60637
Project Title: Single-cell Technologies To Dissect 5hmC And 5mC Heterogeneity In Normal And Malignant HematopoiesisProject Summary:
Blood cells arise from stem cells found in our bone marrow. Through a process called differentiation, stem cells develop into the diverse blood cell types with their various functions. Cells of the same blood subtype are often thought of as homogeneous populations, but this extreme simplification imposes limitations on our ability to understand normal and malignant blood cells. Therefore, it is critical to understand the more complicated reality of blood cell diversity.
Grant: 6556-18 | Translational Research Program (TRP):
Location:Dana-Farber Cancer Institute, Boston, Massachusetts 02215
Project Title: Interaction Of RUNX1 And The Cohesin Complex In Megakaryocyte Development And Myeloid DiseaseProject Summary:
Inherited mutations in the RUNX1 gene cause abnormal platelets and a predisposition to the development of acute myeloid leukemia. Similarly, patients with RUNX1 mutations that are acquired during adult life have an analogous platelet abnormality and predisposition to acute myeloid leukemia. In order for patients with RUNX1 mutations to progress to acute leukemia, additional mutations need to be acquired.
Grant: 5472-18 | Career Development Program (CDP):
Location:British Columbia Cancer Agency Branch, Vancouver, British Columbia V5Z 1L3
Project Title: Roles Of MicroRNA MiR-146a In Hematopoietic Stem Cell FunctionProject Summary:
Myelodysplastic syndrome (MDS) is a cancer of blood stem cells, the blood-forming cells in the bone marrow. In MDS, cancerous blood stem cells lose the ability to make blood cells, and can also block the function of the remaining normal blood cells. Aging and environmental factors are associated with developing MDS, but how these processes affect the function of both cancerous and coexisting normal blood stem cells in MDS remains poorly understood.
Grant: 2317-18 | Career Development Program (CDP):
Location:Washington University in St. Louis, St. Louis , Missouri 63130
Project Title: Targeting Leukemia Stromal Interactions In T-ALLProject Summary:
T-cell acute lymphoblastic leukemia (T-ALL) is a subtype which comprises about 20% of all cases of acute lymphoblastic leukemia. T-ALL is a particularly rare disease in adults, with only about 600 new cases per year in the United States. Furthermore, the prognosis of adults is poor; only 40% of adults with T-ALL are cured with current treatments.
Grant: 5464-18 | Career Development Program (CDP):
Location:Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037
Project Title: The Impact Of Immunoglobulin Isotype (IgM Vs IgG) On B Cell Lymphomagenesis And Progression.Project Summary:
B-cell lymphomas continuously multiply because growth regulation signaling is altered to stay ‘on’ all the time. This signaling is normally triggered by activation of proteins called receptors on the cell surface. Most lymphomas require signaling from a group of receptors called the B-cell receptor (BCR). Normal B-cells produce a type of BCR, called immunoglobulin (Ig), in a process called the germinal center (GC) reaction. There are several types of Ig subtypes – IgM, IgG, and IgA isotypes—which are produced during the GC in response to stimuli generated by agents foreign to the body.
Grant: 3376-18 | Career Development Program (CDP):
Location:The University of Utah, Salt Lake City, Utah 84112-9003
Project Title: Determining The Role Of SIRT5 In Acute Myeloid LeukemiaProject Summary:
Acute myeloid leukemia (AML) is the most deadly blood cancer, with more than 70% of patients dying from the disease within five years after diagnosis. The treatment option shave remained largely unchanged for the past 30 years. Chemotherapy and stem cell transplant are still the standard therapy for AML. The fact that most patients with AML will eventually relapse and succumb to their disease defines an urgent, unmet medical need for more effective drugs to treat this disease. To answer this call, we have taken a novel approach to identify new drug targets.
Grant: 6543-18 | Translational Research Program (TRP):
Location:Children's Research Institute, Washington, District of Columbia 20010
Project Title: Novel Combination Immunotherapies For High Risk Hodgkin's LymphomaProject Summary:
Hodgkin’s lymphoma (HL), a type of blood cancer is largely curable but with significant long-term side effects. Moreover 10-20% of patients are resistant to treatment and difficult to cure. HL is unique that the tumor cells are surrounded by an inhibitory environment that makes the immune system dysfunctional and allows evasion from an effective anti-tumor response. Understanding this environment may provide insight into how we can spur the immune system to attack HL cells effectively.