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Leya Schwartz

As seen in: Science Magazine, BioRxiv
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Articles

Splicing regulatory dynamics for precision analysis and treatment of heterogeneous leukemias

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By Brendon E. Cook, Christina Dold, Helen CHEN, Meenakshi Venkatasubramanian, Leya Schwartz, Nandini Ramachandra, Joshua Bennett, Krithika Subramanian, Xiaoting Chen, Shanisha Gordon-Mitchell, Kith Pradhan, David Shechter, Srabani Sahu, Kashish Chetal, Ariel Fromowitz, Diane Heiser
| Science Magazine Verified
Editor’s summary Dysregulated splicing is a common feature among cancer and creates abnormal protein products that represent promising targets for cancer therapy. Here, Venkatasubramanian et al. developed OncoSplice, an unsupervised computational workflow to define molecular subtypes in cohorts of patients with AML. Inhibition of PRMT5, a nominated regulator of one of their subtypes, was able to block leukemia progression in xenograft AML models.
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Broad de-regulated U2AF1 splicing is prognostic and augments leukemic transformation via protein arginine methyltransferase activation

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By Meenakshi Venkatasubramanian, Joshua Bennett, Leya Schwartz, Nandini Ramachandra
| BioRxiv
Abstract The role of splicing dysregulation in cancer is underscored by splicing factor mutations; however, its impact in the absence of such rare mutations is poorly understood. To reveal complex patient subtypes and putative regulators of pathogenic splicing in Acute Myeloid Leukemia (AML), we developed a new approach called OncoSplice.
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