Grant: 3369-17 | Career Development Program (CDP):
Location:University of Massachusetts Medical School, Worcester, Massachusetts 01655-0002
Project Title: Role Of Nucleosome Remodeling Factors In Regulating ERNA-mediated Gene Expression And Antisense Transcription In ESCsProject Summary:
The majority of mammalian genomes are transcribed, generating a large amount of RNAs that are not converted to proteins, known as non-coding RNAs (ncRNAs). Recently, we found that a specific chromatin regulator, named esBAF, is responsible for repressing the expression of many of these ncRNAs in embryonic stem cells (ESCs). I now propose to further examine the regulation and function of these ncRNAs, specifically focusing on those generated antisense to protein coding RNAs, and those generated at regions that regulate protein coding RNA expression (called enhancer regions).
Grant: 8007-17 | New Idea Award (NIA):
Location:New York University, New York, New York 10012-2331
Project Title: In Silico Assessment Of The Impact Of Changes In Chromatin Organization In Acute LeukemiaProject Summary:
For the first time in human history, rapidly shrinking cost of DNA technologies enables accurate inspection of tumors to an unprecedented level of detail. Each cell in our body contains genetic material (DNA, genes) serving as a set of “instructions” for the proper function of cells. Intriguingly, all cells in our body, no matter what tissue (e.g. skin, liver, neurons) they come from, contain the same instructions, suggesting that these instructions are used differently or selectively in each cell.
Grant: R0818-14 | Quest for CURES (QFC):
Location:University of Connecticut Health Center, Farmington, Connecticut 06030-5335
Project Title: Signalosome-oriented Phosphotyrosine Profiling Of B-cell MalignanciesProject Summary:
Studies have shown that the activity of the B-cell receptor (BCR) and related proteins play a key role in chronic lymphocytic leukemia (CLL) and other B-cell malignancies. Activation of BCR leads to enzymatic activation that creates docking sites for a protein module called SH2 domains. Importantly, the docking of SH2 domains to other proteins is crucial to form a multi-protein complex known as “the BCR signalosome” in B-cells, which is important for regulation of growth and survival in malignant B-cells.
Grant: 6512-17 | Translational Research Program (TRP):
Location:The University of Arizona, Tucson, Arizona 85721-0066
Project Title: A Phase I/II Study Of Haploidentical BMT With Post-Transplant Cyclophosphamide And/or BendamustineProject Summary:
Bone marrow transplantation (BMT) can cure many patients with leukemia or lymphoma. However, finding a matched donor is often difficult, especially for ethnic and racial minorities. Hispanics have only a 37% chance of finding a “perfect-match” in the unrelated donor registry compared to about 80% in Caucasians of European background. Since Arizona is made up of 43% Hispanics and other minorities, nearly 40% of our unrelated donor BMTs end up being less than perfect matches, almost double the national average.
Grant: 6508-17 | Translational Research Program (TRP):
Location:Washington University School of Medicine in St. Louis, St. Louis, Missouri 63112-1408
Project Title: Translating Cytokine-induced NK Cell Memory As Adoptive Immunotherapy For Leukemia PatientsProject Summary:
The long term goal of this project is to translate new findings in the field of Immunology into early phase immunotherapy clinical trials for patients with blood cancers. Acute myeloid leukemia (AML) is an aggressive cancer of blood forming cells that currently has a poor prognosis, with <30% of patients treated with standard therapies achieving long-term disease free survival.
Grant: 6520-17 | Translational Research Program (TRP):
Location:IRIC - Institut de Recherche en Immunovirologie et en Cancerologie, Montreal, Quebec H3C 3J7
Project Title: Development Of Companion Therapies For Poor Outcome HMGA2+ Acute Myeloid LeukemiaProject Summary:
Acute myeloid leukemia (AML) still accounts for a noticeable proportion of all cancer-related deaths. Even today most adult AML patients die within 2 years of being diagnosed, and 25% survive >5 years. The overall goal of this project is to make a major improvement in these statistics through the repositioning or initial development of a new combination therapy and its application using more accurate risk stratification tools.
Grant: 7012-16 | Specialized Center of Research Program (SCOR):
Location:Weill Cornell Medical College, New York, New York 10022
Project Title: Targeting Unmet Clinical Needs For B-Cell LymphomasProject Summary:
Approximately half of lymphoma patients cannot be cured, and even those who are cured must endure significant toxic chemotherapy effects. We lack a full understanding of what makes certain lymphomas resistant. Hundreds of new drugs becoming available are supposed to hit specific molecular targets in lymphomas. However, the task of comparing and contrasting their activity in human lymphomas or models relevant to human lymphomas is daunting since there are thousands of possible dose schedules and combinations. Moreover, we have no way to monitor the activity of most drugs in humans.
Grant: 6503-17 | Translational Research Program (TRP):
Location:The Ohio State University, Columbus, Ohio 43210
Project Title: CS1 Chimeric Antigen Receptor (CAR) T Cells For Treatment Of High-Risk Multiple MyelomaProject Summary:
Multiple myeloma (MM) is the second most frequent blood cancer in developed countries, with effective treatments for most, but those patients with high-risk disease will quickly succumb to the disease. Unprecedented success has recently been reported in other blood cancers with the use of cellular therapeutic targeting via the technology “chimeric antigen receptors (CAR)”, involving the infusion of genetically engineered T cells, which are targeted towards proteins on the tumor cell surface, into relapsed patients.
Grant: 2315-17 | Career Development Program (CDP):
Location:Beckman Research Institute of City of Hope, Duarte, California 91010-3000
Project Title: Cardiovascular Reserve Capacity In Survivors Of Hematopoietic Cell TransplantationProject Summary:
Hematopoietic cell transplantation (HCT) is the treatment of choice for many hematologic malignancies such as acute leukemia and lymphoma. During the past four decades, there have been tremendous advances in HCT, contributing to a growing number of long-term survivors of living in the U.S. today. However, these survivors are at risk for severe and life-threatening complications that can significantly impact quantity and quality of survival.
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.