Grant: 1346-18 | Career Development Program (CDP):
Location:University of Cincinnati, Cincinnati, Ohio 45221-0222
Project Title: The Oncogenic Role And Underlying Mechanism Of TET1 In Acute Myeloid LeukemiaProject Summary:
Acute myeloid leukemia (AML) is one of the most common and fatal forms of hematopoietic malignancies. Thus, it is urgent to better understand the mechanisms underlying the pathogenesis of AML, and on the basis of such understanding, to develop novel therapies with higher efficacy and minimal side effects to treat AML. The properties of cancer are often determined by the proteins that are expressed from information provided by the genes in the cell.
Grant: 5462-18 | Career Development Program (CDP):
Location:Yale University, New Haven, Connecticut 06520-8327
Project Title: A Protein Degradation Approach For The Treatment Of Acute Myeloid LeukemiaProject Summary:
Many cancers result from a genetic mutation causing an “always on” protein. Current treatments are based on the deactivation of the proteins by blocking that protein’s active site. Herein I propose an alternative approach in which proteins are permanently degraded rather than temporarily deactivated, which may prove to be a more favourable form of therapy. To do this, I will take advantage of the cell’s own natural ability to degrade its own proteins when they are in excess or no longer needed.
Grant: 1344-18 | Career Development Program (CDP):
Location:Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024
Project Title: The Biological And Therapeutic Consequences Of SF3B1 Mutations In Myelodysplastic SyndromesProject Summary:
Myelodysplastic syndromes (MDS) are a group of blood disorders characterized by impaired differentiation of hematopoietic stem cells into functional blood cells. MDS frequently has a poor prognosis and is associated with a high risk of transformation into acute myeloid leukemia. There are few treatment options for MDS, largely because the underlying molecular changes that drove MDS were not known until recently.
Grant: 5465-18 | Career Development Program (CDP):
Location:The Regents of the University of California, San Francisco, San Francisco, California 94143
Project Title: Inhibiting The Palmitoylation/Depalmitoylation Cycle As A Selective Therapeutic Strategy In NRAS Mutant Leukemia.Project Summary:
Acute myeloid leukemia (AML) is an aggressive blood cancer that affects children and adults. Recent advances for sequencing the DNA of leukemia cells have greatly advanced our understanding of the genetic causes of AML; however, this new knowledge has not yet resulted in better treatments.
Grant: R0858-18 | Quest for CURES (QFC):
Location:University of Miami, Atlanta, Georgia 30384-5803
Project Title: The Aging Epigenome: Clues To The Pathogenesis Of MDSProject Summary:
Myelodysplastic syndromes (MDS) are diseases of the blood-producing cells in the bone marrow (BM) with a high risk for progression to an aggressive acute leukemia. While rare before the age of 50, its incidence increases significantly with every decade of age and thus it is likely that age-acquired changes in the BM may predispose to the development of MDS. However, the mechanism behind this increased incidence is not fully understood. We propose that as we age, cells in the bone marrow accumulate changes in the nuclear instructions that govern their behavior.
Grant: 3372-18 | Career Development Program (CDP):
Location:The Trustees of Columbia University in the City of New York, Columbia University Medical Center, New York, New York 10027
Project Title: The Role Of Diverse Cytokines Secreted By Myeloid-biased Multipotent Progenitors In Driving LeukemiaProject Summary:
Myelogenous leukemia is a type of blood cancer characterized by the abnormal production of white blood cells in the bone marrow. Abnormally produced white blood cells prevent the proper production of healthy blood cells and eventually lead to failure of the healthy blood system. There are several well-known disease-causing mutations, and many researchers are studying them to find out how the mutations cause disease and to develop treatments based on the targeting of those mutations.
Grant: 5466-18 | Career Development Program (CDP):
Location:The Wistar Institute, Philadelphia, Pennsylvania 19104
Project Title: The Role Of EBNA1 In Epigenetic Regulation Of Gene Expression And EBV LatencyProject Summary:
Epstein-Barr virus (EBV) is a human tumor virus responsible for over 200,000 cancers per year, including multiple blood cancers such as Burkitt’s lymphoma, Hodgkin’s lymphoma, and NK/T cell lymphoma. Like all herpesviruses, EBV can develop a long-term, largely dormant phase called latency, with only occasional reactivation (called the lytic phase). Unlike most other viruses,however, EBV-associated pathogenesis depends on viral latency, rather than an active, lytic infection.
Grant: 3377-18 | Career Development Program (CDP):
Location:Memorial Sloan Kettering Cancer Center, New York, New York 10087
Project Title: Understanding The Effects Of Leukemia-Associated Mutations In Spliceosomal Proteins On Chromatin StateProject Summary:
In the past few years, genetic analysis of leukemias has identified frequent mutations in a class of genes that encodes for proteins participating in a process called RNA splicing. Mutations in RNA splicing factors are now known to be the most common type of mutation in patients with myelodysplastic syndromes (MDS) and related myeloid leukemias as well as chronic lymphocytic leukemia (CLL). These discoveries have resulted in intense efforts to understand how mutations in RNA splicing factors promote the development of leukemia.
Grant: 2318-18 | Career Development Program (CDP):
Location:Charlotte Mecklenburg Hospital Authority d/b/a Carolinas HealthCare System, Charlotte, North Carolina 28203
Project Title: Optimizing Risk And Response Adaptive Strategies Using Immunotherapy In Multiple MyelomaProject Summary:
Despite the more than three-fold improvement in survival outcomes over the last 15 years, multiple myeloma (MM) remains an incurable disease. There is growing recognition that MM disease biology is complex and that personalized treatment strategies need to be developed for different MM patients. However, the current MM treatment paradigm is largely based on a patient’s eligibility for a stem cell transplant. Thus, an incredibly heterogeneous disease is being treated in a ‘one-size-fits-all’ way that translates into broad variability in patient outcomes.
Grant: R0859-18 | Quest for CURES (QFC):
Location:Weill Cornell Medical College, New York, New York 10022
Project Title: Targeting Of The Senescent Vascular Niche To Treat Age-related Hematopoietic Malignancies.Project Summary:
Physiological aging directly leads to a multitude of age-related diseases, including cardiovascular disease, arthritis and cancer, that affect nearly all systems of the body. The goal of this proposal is to identify alterations in the aged bone marrow vascular system that initiate and facilitate the progression of hematopoietic malignancies. We have demonstrated that vascular cells are a critical component of the bone marrow microenvironment and support the overall health and fitness of blood stem cells.