Research We Fund

This research investigates how the PRMT5-p53-DUSP6 axis regulates cytokine signaling in hematopoietic stem cells and its implications for AML (acute myeloid leukemia) cancers. We will use conditional single and double knockout in vivo models to study PRMT5, p53, and DUSP6 roles, and inducible PRMT5 knockdown AML cell lines to examine PRMT5’s impact on cytokine signaling and AML progression. Our goal is to explore the therapeutic potential of PRMT5-p53-DUSP6 regulation.

This project aims to understand why splicing factor gene mutations paradoxically impair the growth of hematopoietic progenitors. We will use mouse competitive transplants to determine if resolution of R-loops with RnaseH1 and/or curtailing Trp53 activation with Mdm4 restores the growth of splicing factor mutant progenitors. Understanding how these progenitors adapt to growth suppressing signals may nominate novel therapies targeting RNASEH1 or TP53 in MDS patients with splicing factor mutations.

Acute myeloid leukemia remains a highly lethal disease. Menin inhibitors are an exciting new class of drugs in leukemic 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 while limiting their toxicity.

Acute myeloid leukemia (AML) is a heterogeneous malignant blood cancer. Its treatment outcome is influenced by the leukemia-driving mutations. Oncogenic NRAS mutations associate with both AML progression, and multi-drug resistance and treatment failure in AML.

We identified a novel combo treatment that greatly improved the survival of leukemia mice through enhancing the leukemia killing activities of T cells. We will investigate its underlying mechanisms and validate it in human AML patient cells