Grant: 6541-18 | Translational Research Program (TRP):
Location:Baylor College of Medicine, Houston, Texas 77030
Project Title: Testing Targeted Therapy In Langerhans Cell HistiocytosisProject Summary:
Rationale and Background: Children with Langerhans cell histiocytosis (LCH) develop destructive lesions that can arise in virtually any organ including bone, brain, liver and bone marrow. LCH occurs with similar frequency as pediatric Hodgkin lymphoma, but there has historically been fewer opportunities for patients with LCH to participate in cancer research studies due to uncertain identity. LCH was first identified over 100 years ago, but only in the past ~5 years has been recognized as a disease in the family of pediatric cancers.
Grant: 6552-18 | Translational Research Program (TRP):
Location:Walter & Eliza Hall Institute of Medical Research, Parkville 3050, Victoria
Project Title: Long-term In Vivo Imaging Of Bone Marrow Microenvironments In Multiple Myeloma.Project Summary:
White blood cells are soldiers of the immune system. These cells are responsible for surveillance of the body and protection from invading pathogens. When the machinery that controls growth and death of these cells is disrupted by genetic mutations, these cells can undergo massive unregulated expansion. This leads to the development of blood cancers such as leukemia and multiple myeloma (MM).
Grant: R0859-18 | Quest for CURES (QFC):
Location:Joan & Sanford I. Weill Medical College of Cornell University, 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: 6548-18 | Translational Research Program (TRP):
Location:Dana-Farber Cancer Institute, Boston, Massachusetts 02215
Project Title: Development Of Histone Lysine Demethylase KDM3A Inhibitors For Multiple Myeloma TherapyProject Summary:
Cancer arises from a series of mutations in the DNA sequence that either activate (turn on) genes that allow cells to grow uncontrollably, or silence (turn off) genes that would normally tell a cell to die if it acquires DNA mutations. However, recent evidence suggests that some cancers inappropriately activate or silence genes through a different mechanism, called epigenetics. Epigenetics refers to chemical modifications to DNA and histone proteins that control gene activity without causing mutations in the DNA sequence.
Grant: 5460-18 | Career Development Program (CDP):
Location:Sloan Kettering Institute for Cancer Research, 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: 5464-18 | Career Development Program (CDP):
Location:Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037
Project Title: The Impact Of Immunoglobulin Isotype (IgM Vs IgG) On B Cell Lymphomagenesis And Progression.Project Summary:
B-cell lymphomas continuously multiply because growth regulation signaling is altered to stay ‘on’ all the time. This signaling is normally triggered by activation of proteins called receptors on the cell surface. Most lymphomas require signaling from a group of receptors called the B-cell receptor (BCR). Normal B-cells produce a type of BCR, called immunoglobulin (Ig), in a process called the germinal center (GC) reaction. There are several types of Ig subtypes – IgM, IgG, and IgA isotypes—which are produced during the GC in response to stimuli generated by agents foreign to the body.
Grant: 1352-18 | Career Development Program (CDP):
Location:New York University School of Medicine, Boston, Massachusetts 02241-415026
Project Title: MicroRNA Regulation Of Leukemia Stem CellsProject Summary:
Acute myeloid leukemia (AML) is composed of two populations of cells with differing characteristics. The bulk population directly gives rise to the disease symptoms. The second population is very small and is composed of leukemia stem cells (LSCs), whose role is to initiate disease and generate the AML bulk population. These self-renewing LSCs are therapy resistant and mediate disease relapse; therefore, it is critical to understand the mechanisms that regulate LSCs in order to develop strategies designed with the intent to cure.
Grant: 6551-18 | Translational Research Program (TRP):
Location:The Board of Regents of the University of Wisconsin System, Madison, Wisconsin 53715-1218
Project Title: Matrix Remodeling In The Myeloma Niche: Implications For Minimal Residual Disease And ImmunotherapyProject Summary:
Despite a revolution in the way we treat myeloma in the last 10-15 years, the disease remains incurable for the vast majority of patients. We have devised powerful novel agents and strategies that kill myeloma cells efficiently, yet not at 100%. Some residual cells remain even after the best of treatments and act as the “seed” from which the disease relapses and ultimately claims human lives. In the last 4-5 years, we have become much better at measuring this “minimal residual disease”. Ultimately however, we should not only recognize and size the enemy, we should eliminate it.