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Evaluating cytokine dependencies in leukemic evolution The earliest stages of leukemia are called clonal hematopoiesis and often occur by DNA mutations in genes that control blood stem cells. Inflammation can drive these mutant cells towards leukemia development. Here we will identify which inflammatory molecules drive clonal hematopoiesis, and will propose methods to intercept leukemia development.

Pyrrolobenzodiazepine-conjugated antibody-drug conjugates for TP53-mutated myeloid neoplasms There are no effective therapies for people with leukemia lacking p53 protein. We developed a new drug called anti- CCRL2 ADC that kills effectively these leukemia cells. We will test this drug in mice and study if combining it with drugs called PARP1/2 inhibitors can make it more […]

Enhancing allogeneic CAR T persistence through gene engineering  CAR T cells are an effective treatment for certain blood cancers, but must be custom made for each patient. Off- the-shelf donor CAR T cells could revolutionize cancer treatment but face challenges with persistence. I aim to improve their longevity by gene editing Zeb-family genes. By blocking […]

Differential Roles Of Stag2 And Rad21 Mutations In Driving Ds-Amkl Transformation And Creating Unique Therapeutic Vulnerabilities Children with Down syndrome face a high risk of acute megakaryoblastic leukemia. This cancer is linked to special changes (mutations) in genes like GATA-1 and cohesin (STAG2, RAD21). We are using patient stem cells to understand how these specific […]

Plasmanylethanolamine Desaturase 1 is essential in leukemia stem cells Outcomes for acute myeloid leukemia (AML) patients are poor due to high relapse rates. AML patients often relapse due to therapy-resistant leukemia stem cells (LSCs). This proposal seeks to examine unique LSC biology and tests a novel strategy to target LSCs, aiming to prevent relapse and […]

Augmenting in vivo CAR T cell therapy with engineered cytokines CAR T cell therapy reprograms immune cells to fight blood cancers but often fails long-term. We’re developing a new approach that engineers these cells directly inside the body and boosts them with a modified immune protein called DR-18. This could make these cancer therapies more […]

Self-Applied Vagus Nerve Stimulation for Chemotherapy Induced Peripheral Neuropathy Chemotherapy-induced peripheral neuropathy causes pain in many cancer survivors. This study tests whether a simple, self-applied ear stimulation device (taVNS) can reduce symptoms. By exploring how taVNS affects inflammation, brain activity, and heart rhythm, findings will guide future research and may offer a simple healthcare option […]

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 […]