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.
Grant: 5460-18 | Career Development Program (CDP):
Location:Memorial Sloan Kettering Cancer Center, New York, New York 10087
Project Title: Defining The Molecular Determinants Of Cysteine Acquisition And Redox Homeostasis In B Cell LymphomaProject Summary:
A key feature of blood cancer cells is the adaptation of their internal cellular metabolism to support nutrient utilization for continuous cell proliferation. Excessive nutrient consumption results in increased levels of reactive oxygen species (ROS). Since increased ROS levels are toxic, there must be countermeasures in place in order for the tumor cell to survive. It is therefore critical for these cancer cells to increase antioxidant capacity in order to overcome the oxidative stress caused by ROS during cancer progression.
Grant: 1350-18 | Career Development Program (CDP):
Location:Brigham and Women’s Hospital, Boston, Massachusetts 02241-3149
Project Title: Enhancing The Clonal Selectivity Of Current Drug Therapies In Myeloproliferative NeoplasmsProject Summary:
The objective of my proposal is to develop better treatments for patients with a group of blood cancers called myeloproliferative neoplasms (MPN). There are currently no curative treatment options for MPN apart from stem cell transplantation, which is a high-risk and sometimes life-threatening procedure.
Grant: 7013-17 | Specialized Center of Research Program (SCOR):
Location:University Health Network, Toronto, Ontario M5G 1Z5
Project Title: Therapeutic Implications Of Altered Epigenetics And DNA Damage Responses In Hematologic DisordersProject Summary:
Acute myeloid leukemia and peripheral T-cell lymphoma are diseases with poor prognosis and limited treatment options. Mutations in three genes with similar functions contribute to the development of both of these diseases, but how they do so is unclear. New therapies targeting the effects of these mutations are being developed, but even the most promising of these are likely to be effective in only a subset of patients. A better understanding of how these mutations contribute to leukemia and lymphoma, and how they affect treatment resistance will lead to new and better therapies.
Grant: 3370-18 | Career Development Program (CDP):
Location:Boston Children's Hospital, Boston, Massachusetts 02241-4413
Project Title: Mechanisms Of Orientation-specific RAG Activity In Mediating V(D)J Recombination And Promoting B Cell LymphomaProject Summary:
A properly functioning human immune system recognizes disease-causing pathogens via a diverse set of antibodies and T cell receptors (TCRs). These molecules, expressed in a subset of white blood cells termed B and T lymphocytes, can bind pathogens and initiate an immune response. The enormous diversity of antibodies and TCRs is generated by the development of lymphoid cells through a DNA “cut-and-paste” process termed V(D)J recombination. The genes encoding the components of the antibodies and TCRs are diversified by the “cutting” and “pasting” of different segments (V, D, and J).