Research We Fund

Children with Down Syndrome (DS) have a 30-fold increased risk of B-cell Acute Lymphoblastic Leukemia (B-ALL). We aim to identify the cells of origin in DS-B-ALL and define its unique features. Using scRNA-seq, we will create an immune cell atlas to study how trisomy 21 (T21) affects lymphopoiesis, and map the cellular and molecular heterogeneity in DS-B-ALL at disease onset and during relapse. These studies will help understand the B lymphoid defects in T21 and how they predispose to DS-B-ALL.

Mutations affecting RNA splicing factors are the most common class of mutations in patients with myelodysplastic syndromes and related myeloid neoplasms. Although these mutations cause a gain of function, there are no treatments which selectively inhibit the enzymatic activity of the mutant spliceosome. To address this issue, here we have developed a new precision therapeutic that selectively target and eliminate cells carrying cancer-causing mutations affecting the RNA splicing factor U2AF1.

Approximately 25% of Acute Myeloid Leukemia (AML) patients are “Primary-Refractory” (P-R) and fail to go into remission with intensive induction chemotherapy. These patients have limited treatment options and overall survival <1 year. We will investigate mechanisms causing chemoresistance through multi-omic studies of a mouse model of P-R AML driven by Mecom overexpression. The goal of this project is to identify potential new therapeutic approaches for P-R AML patients.

A lack of highly selective surface antigens for Acute Myeloid Leukemia (AML) immunotherapy is a major bottleneck in the development of both CAR T cells and T-cell engaging antibodies.  We aim to identify surface-exposed post-translational modifications (PTMs) unique to AML, using high-throughput LC-MS/MS based surfaceomics. By focusing on these distinct PTMs, we hope to develop precision immunotherapies that eliminate AML cells with minimal off-target effects, improving patient outcomes.