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Exploring the role of UCHL1 in leukemia and lymphoma Cellular proteins must occasionally be destroyed in order to maintain the proper functioning of the cell. This is especially true of cancer cells where the destruction of proteins that halt cell division is required for the continued expansion of the cancer. Specific protein removal is the […]

Minimizing Physical Function Decline in Older Adults Receiving Chemotherapy Older adults often develop chemotherapy-associated disability during treatment for acute leukemia which contributes to poor outcomes for these patients. We propose addressing this understudied issue by testing an adaptable exercise program during chemotherapy treatment to improve physical function and quality of life. We anticipate that patients […]

Gene editing in ALL to promote immunomodulatory forms of lytic cell death Cell death removes damaged, pre-malignant, and infected cells. The study of apoptosis has yielded significant insight into the formation and maintenance of leukemia cells: many chemotherapeutics activate apoptotic cell death. We will harness a novel type of inflammatory lytic cell death to promote […]

WT1-targeting adoptive T cell therapy for AML patients at high risk for relapse Although aggressive chemotherapy and stem cell transplantation can cure AML, toxicity is significant and most patients still don’t survive long-term. Transplantation cures are largely due to leukemia-killing immune T cells from the donor. We can genetically engineer a patient’s own T cells […]

Investigating promoter hypermethylation in the biology of MLL-rearranged leukemia, and as a novel target for therapy While the overall cure rate for childhood leukemia is about 80%, children with leukemias that carry mutations in a gene called “MLL” have a much worse prognosis. We have recently discovered that MLL leukemias have a unique tendency to […]

Blockade of the HSP70-BAG3 chaperone/co-chaperone interaction to overcome proteasome inhibitor-refractory multiple myeloma Multiple myeloma still has no cure. Many patients benefit from drugs called proteasome inhibitors, but unfortunately almost all cancers eventually become resistant. Here, we investigate the potential of a new class of drugs, called HSP70-BAG3 inhibitors, to specifically target resistant myeloma leading to […]

Targeting MLL-Cofactor Interaction to Selectively Block Mixed Lineage Leukemia Leukemia often occurs due to chromosomal breakage, which results in mutations that cause blood cells to grow in a disordered and uncontrolled manner. One gene that is often involved in chromosomal translocations that occur in childhood leukemia is the MLL (Mixed Lineage Leukemia) gene. Conventional chemotherapy […]

Study of the Inhibitory Role of miR-26 in the Development of MLL-associated Leukemia Approximately 10% of human acute leukemias are involved in chromosomal translocation between the MLL (mixed lineage leukemia) gene and over 50 partner genes. These leukemias occur preferentially in infant and young children and are often associated with poor outcome. MicroRNAs (miRNAs) are […]

Genomic and Functional Identification of Critical Targets in Peripheral T Cell Lymphoma Peripheral T cell lymphoma (PTCL) is a disease of increasing incidence and poor prognosis. We will combine molecular biology and genomics approaches to analyze the mutations and gene regulatory disruptions that contribute to the malignant biology of PTCL. Armed with novel mechanistic insights […]

The Bcl-6 oncoprotein as a target for transcription therapy Dr. Melnick’s research will focus on determining the mechanism of action of transcription factors (master regulatory proteins that govern the activity of the genome) involved in the molecular pathogenesis of hematologic malignancies. Dr. Melnick and his team discovered a key mechanism of action of a factor […]

The Role of ASXL1 mutations in leukemia patients The development of genomic technologies has uncovered a number of genetic abnormalities in patients with cancer, including acute myeloid leukemia (AML). In large-scale genomic studies we have found that the gene ASXL1 (Addition of Sex Combs-Like 1) is commonly mutated in AML patients. Moreover, we have identified […]

Prospective Validation and Genetic Basis of a Novel Molecular Risk Predictor for Diffuse large B-Cell Lymphoma Drug-development is time consuming and costly, consuming on average 10-years and $800-million for each drug to reach patients. We can circumvent these barriers by designing risk-adapted clinical trials testing new therapies. We developed a method for predicting outcomes for […]