Grant: 5463-18 | Career Development Program (CDP):
Location:La Jolla Institute for Allergy and Immunology, La Jolla, California 92037
Project Title: TET Proteins In B Cell Function And Malignancy.Project Summary:
DNA methylation is a fundamental biological process that controls the activation state of genes, which represent basic modules of biological systems. TET proteins were recently identified as enzymes that mediate the removal of DNA methylation and have been shown to play vital roles in normal development of organisms. Moreover, the activity of TET enzymes is often deregulated during the pathogenesis of various hematological and non-hematological cancers.
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.
Grant: 6537-18 | Translational Research Program (TRP):
Location:Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Project Title: Attenuating Oncogenic Myc-driven Transcription Via Modulation Of The Max Heterodimer PartnerProject Summary:
An emerging therapeutic strategy involves controlling the function of overactive transcription factors that regulate the expression of established disease genes in cancer. As transcription factors have historically proven recalcitrant to drug discovery, several labs are pursuing this opportunity by developing indirect inhibitors of transcription that target various chromatin binding factors as well as kinases that play a role in transcriptional initiation.
Grant: 6546-18 | Translational Research Program (TRP):
Location:Boston Children's Hospital, Boston, Massachusetts 02241-4413
Project Title: Deciphering Epigenetic Cross-talk In Diffuse Large B-cell LymphomaProject Summary:
With an estimated 73,000 new cases of non-Hodgkin lymphoma (NHL) and 20,000 deaths in the year 2016 alone from NHL, novel therapeutic strategies are urgently required. Specifically, the diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL, and contributes about 30% of new NHL diagnosis every year. Our interest in blood biology, and its mis-regulation is several blood disorders including blood cancers, led us to investigate the role of chemical modifications on one of the most fundamental proteins of like- the histone proteins.
Grant: 5459-17 | Career Development Program (CDP):
Location:University of California, San Francisco, San Francisco, California 94143
Project Title: Local Delivery Of Therapeutic Cytokines Via Engineered T Cells In Immunocompetent Mouse Models Of CancerProject Summary:
Lymphomas are malignant tumors derived from lymphocytes, blood cells responsible for fighting infection. Peripheral T-cell lymphomas are some of the most aggressive and difficult to treat forms of this disease. As a result, they are frequently associated with very poor prognosis. We propose that improved understanding of the mechanisms implicated in this disease will facilitate the development of new and more effective therapies. In this context, we have identified mutations in the VAV1 gene in lymphoma samples from peripheral T-cell lymphoma patients.
Grant: 3368-17 | Career Development Program (CDP):
Location:Sloan Kettering Institute for Cancer Research, New York, New York 10087
Project Title: Identifying Therapeutic Vulnerabilities In Spliceosomal-mutant MalignanciesProject Summary:
In recent years, a new class of genetic mutations was discovered in a wide variety of leukemias that have changed the way clinicians and scientists view how leukemia develops. These mutations affect genes that encode proteins that splice RNA and are often some of the earliest mutations found in leukemia patients. They are also very common in forms of leukemia such as myelodysplastic syndromes (MDS) and chronic lymphocytic leukemia (CLL), which makes them very attractive for targeted therapies.
Grant: 8009-17 | New Idea Award (NIA):
Location:Massachusetts General Hospital, Boston, Massachusetts 02241-4876
Project Title: Quiescence Induction By Angiogenin To Improve HSC Function In Bone Marrow FailureProject Summary:
Bone marrow failure (BMF) encompasses a variety of inherited and acquired conditions, which have a common defining feature - impaired ability of the bone marrow to produce blood cells Many important lessons about the biology of the BMF have been learned from studies in genetic animal models of rare human diseases, for example Fanconi anemia. Recent work in mice has shown that in this condition, the bone marrow is excessively "stressed" in response to outside challenges, such as infection or bleeding, and this might account for its inability to produce blood cells.
Grant: 6505-17 | Translational Research Program (TRP):
Location:Children's Hospital Los Angeles, Los Angeles, California 90027
Project Title: Overcoming Drug Resistance In Leukemia Using A Novel Integrin Alpha4 Inhibitor, AVA-4746.Project Summary:
The prognosis of adults treated for ALL is very poor with an overall survival rate of only 40%. Although many children who are treated for acute lymphoblastic leukemia (ALL) are cured, a significant percentage is not, and when this happens the prognosis is grim. Therefore, we need new ideas for treatment of relapsed ALL. Instead of targeting only the leukemia cells, we look at a wider target: the leukemia cells as well as the protective non-leukemia cells that are located in the bone marrow creating a safe haven for ALL cells.
Grant: 6518-17 | Translational Research Program (TRP):
Location:The University of Alabama at Birmingham, Birmingham, Alabama 35294-0111
Project Title: Optimizing Small Molecule Inhibitors Of Heparanase For Myeloma TherapyProject Summary:
Heparanase is an enzyme that is present in high levels in myeloma tumors and its presence is associated with poor patient prognosis. In laboratory studies, when heparanase was present it was shown to promote aggressive myeloma tumor growth, but when heparanase was absent the tumors grew very poorly. These findings suggest that blocking heparanase in myeloma patients will interfere with tumor growth. Although there are several heparanase inhibitors currently available, none of them are specific for heparanase and thus will likely have side effects that could harm patients.