Grant: 5468-18 | Career Development Program (CDP):
Location:New York University School of Medicine, Boston, Massachusetts 02241-415026
Project Title: Understanding The Function Of 3D Chromatin Topology In Myeloid DiseaseProject Summary:
Greater understanding of the fundamental mechanisms promoting the development of acute myeloid leukemia (AML) may help researchers develop new treatment approaches targeting these mechanisms. Chromosomes (collections of DNA and their associated proteins) are heritable and dynamic carriers of genetic information. Chromosomes are constantly looping, and these structural changes shape the gene expression pattern of a cell. This 3D genome landscape, known as genome topology, provides the physical structure required to inform the identity and function of a cell.
Grant: 1351-18 | Career Development Program (CDP):
Location:The Ohio State University, Columbus, Ohio 43210
Project Title: Understanding And Overcoming Resistance To Bruton Tyrosine Kinase Inhibitors In Chronic Lymphocytic LeukemiaProject Summary:
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia and until recently was treated with therapies toxic to the patient. Our clinical and research team at The Ohio State University Comprehensive Cancer Center helped provide critical information which led to the FDA approval of ibrutinib, a less toxic targeted therapy. Ibrutinib inhibits the BTK protein, which is a protein that CLL uses for its own pathological survival. Ibrutinib shows remarkable clinical activity that is more durable than any therapy ever studied in CLL.
Grant: 3374-18 | Career Development Program (CDP):
Location:Brigham and Women’s Hospital, Boston, Massachusetts 02241-3149
Project Title: Functional Characterization Of The Mutant Calreticulin-MPL Interaction In Myeloproliferative NeoplasmsProject Summary:
Myeloproliferative neoplasms (MPN) are a group of rare blood cancers that occur when the body produces too many white blood cells, red blood bloods, or platelets. Though the overall prognosis for MPN tends to be favorable, more advanced forms of these diseases can lead to severe anemia, increased risk of blood clots, and transformation to leukemia. MPN were first described in 1951 by hematologist William Dameshek, but the underlying genetic cause of these diseases remained a mystery for over 50 years.
Grant: 5474-18 | Career Development Program (CDP):
Location:The University of Chicago, Chicago, Illinois 60637
Project Title: Transcriptional And Epigenetic Roles For β-catenin In The Genomic Instability And Oncogenic Transformation Of T-cell Leukemia/lymphomaProject Summary:
Cancer arises from changes in DNA, and these changes can come in various forms. In the case of leukemia and lymphoma, most have genomic instability, meaning the normal organization of DNA (the genome) is disrupted due to improper repairing of DNA breaks. DNA is organized into structures known as chromosomes, and changes to normal chromosomal structure is evidence of genomic instability in a cell.
Grant: 6545-18 | Translational Research Program (TRP):
Location:Brigham and Women’s Hospital, Boston, Massachusetts 02241-3149
Project Title: Targeting Notch In B Cell Lymphoma/leukemiaProject Summary:
Remarkable progress has been made in the treatment of CLL and other B cell tumors such as mantle cell lymphoma, but to date none of these treatments result in cures, and new therapies are needed. Our group has a longstanding interest in targeting the Notch pathway as a cancer treatment strategy. Recently, mutations in Notch genes have emerged as being among the most important causes of CLL and other B cell tumors.
Grant: 6547-18 | Translational Research Program (TRP):
Location:The University of Adelaide, Adelaide, South Australia 5000
Project Title: Targeting Stromal Cell-derived Gremlin1 To Control Multiple Myeloma Disease DevelopmentProject Summary:
Multiple myeloma (MM) is a bone marrow (BM) cancer of antibody producing plasma cells (PC). MM PCs are thought to spread throughout the BM in a manner similar to the way in which solid tumours spread. However, which cells and/or factors within the BM are important in helping PCs establish and grow, remains largely unknown. Using newly developed microscopic and genetic marking techniques: we have shown that there are very few sites within the BM that are capable of supporting the growth of PC tumours.
Grant: 6532-18 | Translational Research Program (TRP):
Location:The Regents of the University of California, San Francisco, San Francisco, California 94143
Project Title: Inducing Effective Anti-leukemic Immunity With Novel AML Vaccines Expressing CD80/IL-15/IL-15R-alphaProject Summary:
Patients with high-risk acute myelogenous leukemia (AML) have poor outcomes because current drug regimens fail to eradicate disease. Transplants of bone marrow or peripheral blood stem cells from matched related, or unrelated donors (allo-transplants) improve survival due to elimination of residual AML by immune cells present in donor cell populations. However, many patients are not eligible for allo-transplants, either because they lack suitable donors, or because they have pre-existing conditions making transplant too risky.
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: R6507-18 | Translational Research Program (TRP):
Location:Dana-Farber Cancer Institute, Boston, Massachusetts 02215
Project Title: MYD88 And CXCR4 WHIM-like Mutations Offer A Targeted Treatment Approach For WMProject Summary:
Ibrutinib is an active drug that is approved by the U.S. FDA and European Medicines Agency for the treatment of WM. WM patients who have a mutation in MYD88 (over 90% do) respond to ibrutinib, while those with mutations in CXCR4 show lower levels of response and delayed responses. Despite the overall high levels of response to ibrutinib among WM patients, the achievement of complete responses is lacking. We discovered as part of the LLS sponsored study that two important pathways exist by which mutated MYD88 can support growth and survival of WM cells.
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.