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Tissue-specific immunity to preserve the graft-versus-tumor effect following hematopoietic cell transplantation Hematopoietic stem cell transplantation (HCT) can cure hematological cancers, but its wider use is limited by the high morbidity and mortality associated with graft-versus-host disease (GVHD). Current therapies for GVHD lead to nonspecific suppression or depletion of T cells, thus potentially compromising the ability […]

Integrative Epigenomics: The Consequences of Kdm6a Inactivation on Chromatin Accessibility and DNA Methylation in Hematopoiesis We will determine if mutations in the gene, KDM6A, which are present in a wide variety of human cancers, are also associated with specific modifications of DNA (DNA methylation) and DNA structure. These associated changes may explain how KDM6A mutations […]

Targeting Cyclin D1 and the DNA Damage Response in Mantle Cell Lymphoma Mantle cell lymphoma (MCL) is rarely curable. Its hallmark is overexpression of the cell cycle regulatory protein cyclin-D1. We uncovered an unexpected role of cyclin-D1 in maintaining MCL genome integrity. We will investigate whether targeting cyclin-D1 simultaneously with proteins that guard against DNA […]

Chemo Resistance to Phase I/II Anti-cancer Agents One of the key limitations of chemotherapy is the development of tumor cells that are resistant to various known chemotherapy drugs. In patients with leukemia or lymphoma who relapse following primary chemotherapy, it is common to try new anti-cancer drugs, many of them in early clinical trials (Phase […]

Identification of Functionally Critical Transcriptional Target Genes in Stem Cells in AML & MDS Despite the use polychemotherapies which reduce the tumor burden, relapse continues to be the most common cause of death in myelodysplastic syndromes (MDS) and acute myeloid leukemias (AML). Recent evidence demonstrates that rare so-called leukemia stem cells (LSC) give rise to […]

Cytokine-Induced Memory-Like NK Cells For Adoptive Immunotherapy of AML. Recent scientific advances have shown that cytokine activation results in cytokine-induced memory-like (CIML) NK cells with superior anti-leukemia activity. We will translate CIML NK cells into a first-in-human clinical trial for acute myeloid leukemia patients. Correlative studies will evaluate CIML NK cells expansion, survival, activation, and […]

Vibration Intervention for Bone Enhancement in Childhood Cancer Survivors Interventions to improve Bone Marrow Density (BMD), and prevent early onset osteoporosis and fracture are essential to promote long, productive lives, free from persistent pain and/or disability. Current treatments for BMD decrements among childhood cancer survivors are limited to those who can tolerate a pharmacologic agent, […]

The Role of AML/1ETO in the Pathogenesis of t(8;21) Acute Myeloid Leukemia This year, approximately 10,500 adults will be diagnosed with acute myeloid leukemia (AML) in the U.S. Despite incremental improvements in the care of these patients over the past three decades, most will die of their disease. My laboratory is studying the AML subtype […]

The Memorial Sloan-Kettering Cancer Center’s Integrative Medicine Service’s Music Therapy Program brings music to the bedside of hundreds of patients by trained, credentialed professionals who tailor their offerings to the needs of individuals and their family members. This vital service is offered to both patients and their families providing therapists who work closely as part […]

Splicing and Epigenetic Control of Hematopoiesis in MDS and Leukemia The discovery of new cancer mutations brings the reality of targeted therapy into reach; if we can understand how the mutations work and which other factors are involved. Our research will address these questions and lead to new therapies that will selectively kill mutant cells […]

Defining the role of the inv(16)-encoded CBFA2T3-GLIS2 chimeric transcription factor in the pathogenesis of pediatric acute megakaryoblastic leukemia We have identified a mutation that fuses two genes together resulting in an aberrant protein, CBFA2T3-GLIS2, in ~1/3 of pediatric acute megakaryoblastic leukemia patients. We have demonstrated that this protein enhances the cell’s ability to self-renew. Our […]

miR-23a Cluster and miR-10a Regulation of Self-Renewal and Survival Pathways in Human Hematopoietic Stem-Progenitor Cells and Acute Leukemia Cells The goals of this project are to investigate the regulation of genes and pathways involved in self-renewal and survival pathway in leukemia stem cells (LSCs) by small molecules called microRNA. Two of these microRNAs, the mir-23a […]