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Targeting Inflammation Within The Tumor Microenvironment for Cancer Therapy Inflammation is a key determinant of cancer progression. Dr. Beatty’s research uses a mouse model of cancer that faithfully reproduces inflammation within the tumor microenvironment as is seen in human cancers. Using this model, he has found that macrophages linked to cancer can be therapeutically targeted […]

Identifying vulnerabilities in hematologic malignancies driven by heterotrimeric G proteins Blood cancers arise from cells that acquire mutations before becoming a leukemia. We study a gene called GNB1 that is often mutated in patients with “pre-leukemic” blood cells, and in leukemia and lymphoma. We will determine how best to target GNB1 mutant cells to treat […]

Molecular Rationale for WNT Inhibitor Therapy in B-Cell Lymphoma The FOXP1 protein is overexpressed in B-cell lymphomas, and patients with high FOXP1 levels often resist therapy and are given a poor prognosis. We discovered that FOXP1 activates the WNT signaling pathway. We will determine whether WNT inhibitors currently in clinical trails for other cancers will […]

An Integrative Approach to the Control of Intractable Pain from Cancer such as Multiple Myeloma The relief of suffering is a high priority for patients with cancer and their families. Advanced cancers frequently cause severe chronic pain because of cancer spread to the bones and internal organs. Progress in pain treatment has been achieved over […]

Dynamic Changes in MDS Clonal Architecture During Treatment with Hypomethylating Agents

The Role of Mutations in Epigenetic Regulators in Myeloid Leukemia Cure rates for AML patients have not substantially improved in the last 40 years. To keep pace with the genomics revolution, the focus of this project is to develop model systems that more closely resemble the natural history of cancer to understand how different mutations […]

TGF beta receptor inhibition as a therapeutic strategy in Myelodysplastia Myelodysplastic syndromes (MDS) are pre-leukemic conditions that lead to decreases in blood counts in the elderly and do not have many treatment options. Dr. Verma has determined that a protein, Transforming Growth Factor-beta (TGF), is partly responsible for suppressing the growth of stem cells in […]

Activation of Signal Transduction Pathways in Leukemia Leukemia is a disease in which the bone marrow produces an abnormally high number of white blood cells that do not mature into normally functioning white blood cells capable of fighting infection. There is considerable evidence that both normal hematopoietic cells (precursor cells that mature into functional blood […]

T-Cells to Control the Graft-Versus-Host Effect of Nonmyeloablative Hematopoietic Cell Transplantation The aim of this project is to develop T cells to help further reduce the toxicity of bone marrow transplantation. Bone marrow transplantation, also known as hematopoietic cell transplantation, is the only curative treatment available for many patients with passive apostraphe leukemia and lymphoma. […]

The Molecular Genetics of Acute Megakaryocytic Leukemia AMkL accounts for 15% of childhood AML and has a very poor prognosis. Although a few chromosomal abnormalities have been identified in AMkL, the genetic lesions underlying most cases remain unknown. Recent transcriptome analysis of AMkL performed in Dr. Larson’s laboratory identified a novel inv16(q24.3;p13.3) encoding a CBFA2T3-GLIS2 […]

Blockade of autocrine signaling for curative therapy of acute myeloid leukemia Acute myeloid leukemia (AML) is a blood cancer that frequently affects both children and adults. Current treatment of AML with chemotherapy is toxic, and new therapies are direly needed for patients whose disease is resistant to intensive chemotherapy. Our research into molecular signaling pathways […]

New approaches to Haploidentical Hemopoietic Cell Transplant Allogeneic hematopoietic cell transplantation (HCT) is a potential curative treatment for lymphomas, myeloma and leukemias. In absence of a related or unrelated matched donor, the most relevant hematopoietic cell source is a partially-matched (haploidentical) related donor sibling, child or parent. Unfortunately the use of haploidentical donor is limited […]