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Therapeutic Targeting of the BCL6; p53 axis with Histone Deactylase Inhibitors in Diffuse Large B-Cell Lymphoma Diffuse large B-cell Lymphoma (DLBCL), the commonest form of lymphoma, affects 20,000 people yearly. Bcl6, a critical protein involved in DLBCL, allows cancer cells to grow uncontrollably. p53, another crucial protein, turned off in DLBCL, ordinarily destroys pre-cancerous cells. […]

Diverse Genetic Etiologies Dysregulate the Novel Gene Target, TNK2, in Hematologic Malignancies

Development Context and Germline Variation in Infant Leukemogenesis Infant leukemia is a hard to treat malignancy of childhood with a grim prognosis. The proposed studies will provide insights into how inherited genetic differences among children may predispose to infant leukemia. This will improve our ability to counsel families and treat this disease.

To Collect Peripheral Blood and Bone Marrow Samples from Donors and Recipients of Blood and Marrow Transplants for Laboratory Research In his ongoing studies of anti-leukemia immunity and CTL antigens, Dr. Molldrem has studied myeloid-restricted normal proteins that are highly expressed leukemia. Myeloid leukemias express a number of differentiation antigens associated with granule formation. He […]

Bcl-2 Family Proteins as Metabolic Targets in Leukemia It was established in the early 1900s that cancer cells have increased rates of glucose metabolism. While inhibition of this metabolic program in cancer cells may provide a novel avenue for future cancer treatment, a lack of understanding how metabolic stress can cause cell death has precluded […]

In Vivo Models for Design and Optimization of Targeted Nanocarriers (Protocells) for Leukemia Therapy

Cell Death Regulation by Pro-Apoptotic BOK in Multiple Myeloma Although the chemotherapeutic bortezomib has dramatically improved the survival of myeloma patients, nearly everyone develops resistance. We identified that a protein called BOK, which is frequently deleted in cancer, coordinates multiple ways cells die in response to bortezomib. We aim to identify therapeutic targets to re-activate […]

Targeting NOXA methylation to overcome Bortezomib resistance in MCL Mantle cell lymphoma is an aggressive type of non-Hodgkin’s lymphoma characterized by frequent relapses and usually fatal in the majority of patients. We are trying to understand precisely why patients do not respond to Bortezomib, a standard chemotherapy for this disease using cutting-edge next generation sequencing […]

Novel approaches to enhancing the therapeutic index of chimeric antigen receptor T cell therapy for acute myeloid leukemia The aim of this project is to develop a technology that will allow a powerful immune cell attack against leukemia without damaging normal bone marrow cells, thereby increasing the safety of cancer immunotherapy.

Molecular Therapy of CNS Lymphoma Dr. Rubenstein’s team is investigating new approaches in the use of Rituximab, a monoclonal antibody which is an important drug in the treatment of non-Hodgkin’s lymphoma. Rituximab is the first antibody to be approved in the treatment of cancer and is currently used in the vast majority of patients with […]

Investigating the collaboration between microRNAs and oncogenes in leukemia Understanding the mutations that cause leukemia is critical to our ability to design novel therapies. We propose to determine the capacity of two molecules, which are found mutated together in human AML patients, to collaborate during initial leukemic transformation and later during resistance to therapies.

Targeting NEDD8 protein conjugation: a novel therapeutic strategy for acute lymphoblastic leukemia (ALL). Acute lymphoblastic leukemia (ALL) is the main cause of cancer related death in children. We have access to a brand new drug that kills these leukemia cells very effectively in the laboratory. We want to study this drug in detail and test […]