Posts found in:
Grantees

Enhancing Menin Inhibition in Acute Leukemia by Activating p53 Acute myeloid leukemia remains a highly lethal disease. Menin inhibitors are an exciting new class of drugs in leukemia but are rarely curative and have significant toxicities. We seek to develop a new treatment approach for patients with leukemia by enhancing the effects of Menin inhibitors […]

Targeting T regulatory type 1 cells for cancer immunotherapy Regulatory cells can hinder successful cancer immunotherapy. We found regulatory Tr1 cells, usually seen in autoimmune diseases, in lymphoma tumors. Our previous work suggests the drug ibrutinib might reduce Tr1s. We will study how ibrutinib blocks Tr1s and seek new strategies for Tr1 blocking so we […]

Investigating chromatin biomarkers for therapeutic sensitivity to Menin inhibition in myeloid malignancies Cellular DNA is structured as “open” or “closed” chromatin fibers which influences whether genes can be activated/de-activated. Chromatin structure is markedly perturbed in myelodysplastic syndrome and acute myeloid leukemia. This translational proposal tests the hypothesis that “open-ness” of MEIS1 target genes is a […]

Leveraging comparative oncogenomics to nominate therapeutic targets for hypodiploid B-ALL. Hypodiploid B-cell Acute Lymphoblastic Leukemia (B-ALL) is a disease from which few survive. Developing treatments for this disease has been challenging because we did not have the tools to study it. We have developed novel experimental tools, namely animal models, that are allowing us to […]

Clonal Evolution and Epigenetic Plasticity drive Resistance to Hypomethylating Agents in Myelodysplastic Syndrome The proposed project explores why some Myelodysplastic Syndrome (MDS) patients become resistant to a common treatment. By studying genetic and epigenetic changes in single cells from patients, we aim to uncover the mechanisms driving this resistance. Our findings could lead to better […]

Interrogating the contribution of lymphodepletion to effective CAR T cell therapy The success of CAR T cell therapy is dependent on administration of lymphodepletion, but how this enhances treatment outcomes has not been rigorously examined. We propose to dissect the mechanism of lymphodepletion support of CAR T cells to maximize their anti-tumor benefit in hematologic […]

A Decentralized Trial of a High-Fiber Plant-Based Dietary Intervention in Clonal Hematopoiesis Clonal hematopoiesis (CH) is an age-related disorder that affects the blood cells and often leads to inflammation, cardiovascular disease, and blood cancer. We aim to study the effects of a high-fiber plant-based diet on quality of life; inflammation; and cell, tissue, and organ […]

Leveraging the gut microbiome in lymphoma CAR T-cell therapy CAR T-cell therapy shows promise for lymphoma, but success rates vary. We propose that deliberate microbiome perturbation could enhance anti-tumor activity during specific therapy moments. With machine-learning analysis of patient data and experiments, we investigate microbiome perturbation strategies that activate and redistribute innate immune cells for […]

Synthetic lethality as a therapeutic strategy for diffuse large B-cell lymphoma We propose a new DLBCL treatment using a concept called synthetic lethality. Synthetic lethality happens when changes in two genes cause cells to die, but a change in either gene alone does not. This approach selectively targets DLBCL with specific changes in specific genes, […]

Novel approaches to therapeutic targets for SF3B1 mutated leukemias Many leukemias have mutations in the SF3B1 gene. Its function is to “stitch together” RNA correctly. RNA is akin to a manufacturing blueprint for making proteins. When mutated, SF3B1 makes abnormal RNA and thus abnormal proteins. We are studying how to target these abnormal RNAs and […]

Elucidating the mechanisms of response and resistance to bispecific antibody therapies in indolent B-cell non-Hodgkin lymphomas Bispecific antibodies, which have emerged as a potent treatment for patients with B-cell lymphomas, activate immune-mediated killing of cancer cells. The proposed research will determine the cellular actors that drive initial and sustained responses to this novel class of […]

Deciphering and Targeting Epigenetic Reader Dependencies in Acute Myeloid Leukemia MLL-rearranged acute myeloid leukemia is an aggressive form of leukemia with poor survival outcomes. In our proposal, we focus on a unique, druggable epigenetic reader crucial for the disease’s progression. By further evaluating this reader, our research could unveil new avenues for more targeted treatments […]