O. Abdel-Wahab

Covalent Targeting of Splicing in T Cells.

This study develops chemical probes to target splicing factors in T cells, showing state-dependent loss of ITK via SF3B1 and demonstrating covalent ligandability of splicing regulators.

A mitochondrial surveillance mechanism activated by SRSF2 mutations in hematologic malignancies

This study shows that SRSF2 mutations disrupt mitochondrial mRNA splicing, impair complex I function, and increase mitophagy through a PINK1 splicing mechanism, identifying mitophagy as a therapeutic target in MDS and AML.

Imetelstat-Mediated Alterations in Fatty Acid Metabolism To Induce Ferroptosis As Therapeutic Strategy for Acute Myeloid Leukemia

This study identifies ferroptosis as a mechanism by which imetelstat induces therapeutic effects in AML, showing that targeting fatty acid metabolism enhances its efficacy.

Proteomic discovery of chemical probes that perturb protein complexes in human cells

This study develops a proteomic strategy to identify chemical probes that perturb protein complexes in human cells by analyzing electrophilic compounds' effects on protein interactions.

Splicing modulators impair DNA damage response and induce killing of cohesin-mutant MDS/AML

The paper shows SF3B1 splicing modulators impair DNA damage response in cohesin-mutant MDS/AML, leading to increased sensitivity to PARP inhibitors and chemotherapy.

Single-cell multi-omics defines the cell-type specific impact of splicing aberrations in human hematopoietic clonal outgrowths

This study introduces GoT-Splice, a multi-omics method to analyze splicing aberrations in human hematopoietic cells, revealing cell-type specific effects of SF3B1 mutations in clonal outgrowths.

Integrated Single-Cell Genotyping and Chromatin Accessibility Charts JAK2V617F Human Hematopoietic Differentiation

This paper develops GoT-ChA to link genotypes to chromatin accessibility in single cells, revealing JAK2V617F mutation-induced epigenetic changes in hematopoietic differentiation.

Single-cell multi-omics of human clonal hematopoiesis reveals that DNMT3A R882 mutations perturb early progenitor states through selective hypomethylation

This study uses single-cell multi-omics to show DNMT3A R882 mutations cause hypomethylation and alter progenitor cell fates in clonal hematopoiesis.

Sex-biased ZRSR2 mutations in myeloid malignancies impair plasmacytoid dendritic cell activation and apoptosis

The paper identifies sex-biased ZRSR2 mutations in BPDCN that impair pDC activation and apoptosis, linking X chromosome mutations to male-predominant leukemia.

High throughput droplet single-cell Genotyping of Transcriptomes (GoT) reveals the cell identity dependency of the impact of somatic mutations

This study introduces GoT, a high-throughput method linking single-cell genotypes and transcriptomes, revealing that somatic mutations' transcriptional effects depend on cell identity.

Impaired hematopoiesis and leukemia development in mice with a conditional \"knock-in\" allele of a mutant splicing factor gene U2af1

This paper generates a mouse model with a conditional knock-in of the U2af1(S34F) mutation to study its role in hematopoiesis and leukemia, finding that it requires additional mutations for leukemogenesis.