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Mechanisms by which GSK3β inhibition enhances nonhomologous end-joining repair of IR-induced double strand breaks Neurocognitive deficits from cranial irradiation are serious side effects from treatment of leukemias, especially in children. We have previously found that lithium, an inhibitor of the enzyme glycogen synthase kinase-3_ (GSK3_), can protect neurons but not cancer cells from radiation induced […]

Mer Tyrosine Kinase as a Cooperative Oncogene in Leukemogenesis Tyrosine kinases are a family of proteins that are directly linked to multiple types of human cancer. Dr. Graham is investigating the role of a tyrosine kinase, Mer, in childhood T cell leukemia and lymphoma. The Mer protein is not expressed in normal lymphocytes but is […]

Regulation of Leukemia Cell Dormancy by the Bone Marrow Microenvironment While the majority of patients respond to initial therapy for leukemia, many will experience disease relapse. Leukemia cells need to be actively dividing to be susceptible to most chemotherapies; cells that are not actively dividing, or are “dormant” during chemotherapy, can therefore contribute to recurrence. […]

A Randomized Trial of Physical-Activity Motivation in Breast Cancer Patients. Research shows that exercise can prolong survival in cancer patients. A major challenge, however, is to engage patients in sustained physical activity. Research has yet to determine which motivators are optimal. We propose to fill this gap with a randomized study of two incentives that […]

Translational Regulation of Gene Expression in Acute Myelogenous Leukemia (AML) Dr. Sternberg’s laboratory is committed to the development of therapeutic strategies for leukemia through knowledge of aberrant information signaling within the cancer cell. The generation of leukemias is caused in many instances by mutation of rogue oncogenes that disrupt normal cell signaling. Two of these, […]

Cytokine Release Syndrome in Immunotherapy Most children with cancer can be cured by standard therapies yet some cancers will be resistant or will relapse. Recent therapies using modified immune cells have shown great promise, but also make patients very ill. I propose to investigate these modified immune cells in order reduce untoward side effects.

Defining the role and therapeutic potential of TNF receptor-associated factor 6 in Myelodysplastic Syndromes

Metabolic regulation of leukemia stem cells We will determine the role of AMPK in AML using mouse models and identify the key metabolic pathway regulated by AMPK that maintains AML-initiating cell population. Our goal is to understand how AML cells maintain metabolic integrity to develop new therapies targeting this common requirement of cancer.

Introducing next generation sequencing for the diagnosis of myeloproliferative neoplasms (MPN) We wish to improve the accuracy and cost-effectiveness of tests to diagnose the pre-malignant and malignant blood cancers, known as the myeloproliferative disorders (MPD). Together with two other large UK clinics, we will assess modern techniques (next generation sequencing) as a replacement for the […]

Genetic Complexity of Quiescent Leukaemic Stem Cells Childhood acute lymphoblastic leukaemia (ALL) patients respond initially well to chemotherapy, but some relapse due to the proliferation of treatment-resistant dormant cells. We have demonstrated that leukaemia patients have different sub-clones, so no we aim to investigate which of these sub-clones contains dormant cells responsible for subsequent relapses.

Therapeutic targeting of cancer stem cells in mouse and human myelodysplastic syndromes Myelodysplastic syndromes is a hematologic malignancy driven by rare cancer stem cells defective in their ability to generate mature blood cells. Our goal is to identify drugable targets that can restore the cancer stem cells’ ability to generate functionally normal blood cells, thereby […]

Pathogenesis of Aggressive B Cell Lymphoma We seek to understand how the control systems of normal cells become corrupted during the process of lymphoma development. In doing so, we aim to identify cancerous pathways that can be inhibited by novel drugs in a way that specifically targets the cancerous cells while leaving normal cells intact.