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T-Cell Gene Transfer and Therapy by the Sleeping Beauty Transposon System The objective of this application is to test whether a novel, naked DNA based vehicle, Sleeping Beauty transposon, can express therapeutic molecules in human T cells for the treatment of leukemia and lymphoma. The rationale for the proposed research is based on Dr. Zhou’s […]

The Function and Regulatory Mechanism of miR-495 in Acute Myeloid Leukemia (AML) MLL-rearranged leukemia, accounting for approximately 10% of human acute leukemias, is often associated with poor prognosis.MicroRNAs (miRNAs) are a class of small RNAs mediating gene silencing. I found that miR-495 was significantly down-regulated in most AML cases with MLL rearrangements. It dramatically inhibited […]

Complementary Approaches for Treating Acute Lymphoblastic Leukemia (ALL): A Mouse ALL The aim of this project is to develop and employ complimentary and alternative approaches for treating pediatric ALL (Acute Lymphoblastic Leukemia patients). However, prior to testing such approaches in pediatric patients, potential therapies should be tested in animal models. In recent years, several good […]

Hedgehog signaling as a stem cell based therapeutic target in myelodysplastic syndrome and acute myeloid leukemia. In many ways the growth of cancer mirrors the formation of normal organs during embryonic development. Dr. Matsui has found that a specific pathway required during development called the Hedgehog signaling pathway is abnormally turned on in acute myeloid […]

Targeting leukemic stem cells in infant leukemia by blocking interactions with the microenvironment While childhood acute lymphoblastic leukemia is very curable, leukemia in infants less than six months of age is very difficult to cure. Better approaches to treatment targeting leukemia cells and leaving normal cells alone are highly desirable for these tiny patients. Dr. […]

T cells to Enhance Umbilical Cord Blood Transplantation Umbilical cord blood transplantation is potentially life-saving for patients with otherwise incurable leukemia and lymphoma, but is still limited by delayed recovery of normal blood cells, risk of infections and the risk of disease returning. My research focuses on understanding, employing and activating T cells to address […]

A Pilot Study Evaluating the Microbiome and Obesity in Pediatric Acute Lymphoblastic Leukemia Pediatric ALL is a risk factor for the development of obesity. Children who develop obesity have reduced survival and increased side-effects. The intestinal microbiota has a role in the development and treatment of obesity. We propose to evaluate the intestinal microbiota so […]

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, […]