Research We Fund

Despite an array of promising immunotherapies, the blood cancer multiple myeloma still remains without any known cure. Patients with high-risk disease in particular still relapse most frequently after current BCMA-targeting therapies such as CAR-T cells. Here we identify CD70 as an alternative CAR-T target in these high-risk patients who need new treatment options, and further use innovative artificial intelligence-inspired strategies to develop a best-in-class CAR-T design targeting CD70. The goal of our proposal is to perform additional validation studies to prove the efficacy and safety of this novel CAR-T cell, with the goal of moving toward near-term clinical trials in high-risk myeloma by the completion of the award period.

The identification of critical therapeutic targets in myeloproliferative neoplasm (MPN) cells will have a significant impact on the development of much needed treatments for the 300,000 MPN patients in the U.S. Deregulated activity of a protein called JAK2 is an important factor that contributes to MPN formation, but currently approved drugs targeting JAK2 have had limited success, as disease-driving cells persistently survive therapy, and thus these drugs can not readily induce remission in patients. After four decades of the identification of the importance of a protein called RAS in cancer, which is also involved in the cancer causing signaling of JAK2 in MPN, an innovative drug has just been developed (in 2024) to directly block RAS activity. This proposal will investigate the potential this exciting new drug may have in novel therapeutic approaches to improve the lives and the long term health and outcomes of MPN patients.

Our objective is to develop a highly specific T-cell engaging therapy to treat a subtype of leukemia that currently lacks effective treatment. We also aim to minimize toxicity to healthy blood cells, a common challenge with existing leukemia immunotherapies.

This project aims to uncover how obligatory heterozygous mutant splicing factors (SF) impact their wildtype counterparts’ functions, RNA interaction sequences and the epitranscriptome and translatome, to identify convergent pathways and novel therapeutic approaches. I will utilize cell lines, mouse models and primary patient samples. I will leverage a spatial spliceoform RNAseq approach to decipher SF mutations’ impact on cell-cell interactions in the bone marrow microenvironment.