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Revealing novel SMARCA4-related dependencies in mixed-lineage leukemia Mixed-lineage leukemia (MLL) is an aggressive blood cancer affecting ~ 5,000 infants in the U.S. each year. Unlike other types of childhood leukemia, MLL has few treatment options and a five-year survival rate of only 40%. Through our studies, we will identify and validate entirely new precision approaches […]

Targeting Mammalian SWI/SNF (BAF) Chromatin Remodeling Complexes in Leukemia and Lymphoma Several types of leukemia are dependent on protein complexes inside the cell that regulate the architecture of the genome, called chromatin remodeling complexes. Our work seeks to understand the mechanisms underpinning the importance of these complexes in leukemia, which will inform new therapeutic strategies.

Post-translational regulation of splicing as a pro-oncogenic mechanism in high-risk T cell leukemia Chemotherapy for acute lymphoblastic leukemia entails burdensome side-effects, a risk of second cancers and associated resistance. We have identified a mechanism that controls how genes leading to leukemia behave and we aim to exploit this knowledge in order to identify new treatment […]

Hacking cytokine pathways for precision cancer immunotherapy The immune system is controlled by a molecular “internet” of protein messages called cytokines. Here, we propose to “hack” into a specific cytokine signal (IL-18) to instruct killer lymphocytes to attack cancers via a message that cannot be overridden. These “hacked” cytokines may thus represent promising candidates for […]

Biological Consequences and Therapeutic Implications of Beta-arrestin2 loss in aggressive Lymphomas The primary and acquired resistance of lymphoma cells to standard chemotherapy continues to pose a serious problem for patients and clinicians. Our proposed study will explore a novel mechanism by which lymphoma cells become resistant to therapeutic intervention.

Long non-coding RNAs in T-cell lymphoma Mutations of lncRNA Rmrp and its associated factors result in immune-deficiencies and blood malignancies in human. We propose to investigate how this molecule facilitates the normal development and function of white blood cells in the immune system and determine how changes to its structure promote lymphoma.

Long non-coding RNAs in T-cell lymphoma Mutations of lncRNA Rmrp and its associated factors result in immune-deficiencies and blood malignancies in human. We propose to investigate how this molecule facilitates the normal development and function of white blood cells in the immune system and determine how changes to its structure promote lymphoma.

The role of miR-126 in core-binding factor acute myeloid leukemia Acute myeloid leukemia (AML), one of the most common types of leukemia, is a cancer of blood cells that originate in the bone marrow. Two common subtypes of AMLs are associated with chromosome rearrangements, such as translocations between chromosome 8 and 21 or inversions within […]

Killing Two Birds with One Stone: Dual Modal Gene Therapy for Leukemia Using Chimeric Nanoparticles Genetic mutations in cancer cells reduce activity of molecules that cause cell death, leading to imbalanced cellular signals and prolonged leukemia cell survival. This project aims to genetically re-balance the molecular signals toward programmed death in leukemia cells. We will […]

Therapeutic effect of Boswellia Carterri Birdw in Acute Myelocyctic Leukemia Traditional Chinese Medicine is a potential source for modern cancer therapies but western technology and clinical trials are required properly to identify, understand, and evaluate the active components. This is best exemplified by the dramatic clinical responses to all trans retinoic acid and arsenic trioxide […]

Targeting Slit2/Robo4 Signaling as a Novel Treatment for Leukemia Slit2/Robo4 signaling modulates localization of hematopoietic stem cells to bone marrow (BM) vascular niches (VN), which are also involved in the pathogenesis of acute myeloid leukemia (AML). Using a BMVN model, we will examine the effects of Slit2/Robo4

Development of drugs that downregulate microRNAs associated with drug resistance A key issue in the treatment of acute leukemias, as well as other cancers is the development of resistance. Recently a small set of microRNAs (miRs) including miR-125b were found to be associated with drug resistance in acute lymphoblastic leukemia patients. In this proposal, Dr. […]