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Applying synthetic lethality to eradicate high risk NF1-deficient B-cell acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a leading cause of cancer-related pediatric death. Many ALL patients are cured but specific sub-types of ALL are lethal. We have developed a new therapy that exploits a common feature of these poor prognosis pediatric leukemias and propose […]

Targeting ‘undruggable’ initiating events in AML Acute myeloid leukemia is a devastating illness with approximately 600 pediatric and 13,000 adult diagnoses, and 10,000 deaths, yearly. In this proposal we will develop prototype drugs that destroy the aberrant components, or proteins, within the cell that drive the malignant phenotype laying the groundwork for development of first-in-class […]

MYC-dependent replication stress as a pathogenic driver and therapeutic target in aggressive B cell lymphomas B cell lymphomas with MYC gene alterations are very aggressive and not curable using current therapies. Targeting MYC would thus be an ideal therapeutic strategy in these patients. Here, we describe a cellular process representing a unique vulnerability in MYC-driven […]

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 […]