A5042323995- RNA Research and Splicing
- RNA modifications and cancer
- Protein Degradation and Inhibitors
- Protein Kinase Regulation and GTPase Signaling
- Virus-based gene therapy research
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- Pluripotent Stem Cells Research
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Neuroblastoma Research and Treatments
- Cellular transport and secretion
- PI3K/AKT/mTOR signaling in cancer
- Lung Cancer Research Studies
- Growth Hormone and Insulin-like Growth Factors
- Neuroendocrine Tumor Research Advances
- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Lymphoma Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
Memorial Sloan Kettering Cancer Center
2020-2025
Kettering University
2023
Increasing use of covalent and noncovalent inhibitors Bruton's tyrosine kinase (BTK) has elucidated a series acquired drug-resistant BTK mutations in patients with B cell malignancies. Here we identify inhibitor resistance distinct enzymatic activities, including some that impair activity while imparting novel protein-protein interactions sustain receptor (BCR) signaling. Furthermore, describe clinical-stage IKZF1/3 degrader, NX-2127, can bind proteasomally degrade each mutant proteoform,...
Ongoing, early-stage clinical trials illustrate the translational potential of human pluripotent stem cell (hPSC)-based therapies in Parkinson's disease (PD). However, an unresolved challenge is extensive death following transplantation. Here, we performed a pooled CRISPR-Cas9 screen to enhance postmitotic dopamine neuron survival vivo. We identified p53-mediated apoptotic as major contributor loss and uncovered causal link tumor necrosis factor alpha (TNF-α)-nuclear κB (NF-κB) signaling...
Highlights•GPATCH8 is required for mutant SF3B1-dependent splicing alterations•GPATCH8 involved in quality control of intronic branchpoint selection•GPATCH8 opposes activity SUGP1, and each competes interaction with DHX15•Deletion GPATCH8 corrects aberrant differentiation SF3B1-mutant MDS cellsSummaryMutations the RNA factor gene SF3B1 are common across hematologic solid cancers result widespread alterations splicing, yet there currently no therapeutic means to correct this mis-splicing....
Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading poor prognosis. Up date, even if patients at high risk can be identified by the occurrence Tumor Protein P53 (TP53) Retinoblastoma Transcriptional Corepressor 1 (RB1) mutations their tumors, no therapeutic strategies are available prevent or delay histological transformation. Upregulation cell cycle kinase Cell Division Cycle 7 (CDC7) occurred tumors during initial...
Recent phase 3 clinical trial showed improved radiographic progression-free survival in PTEN-deficient prostate cancers treated with combined Akt and AR inhibition. Building on this our previous research into PI3K signaling interactions, we aimed to define the mechanisms of response resistance We discovered that restoration mTOR was early dominant driver Mechanistically, can be achieved through molecular alterations, resulting loss negative regulators mTOR. Unexpectedly, dominated by...
To identify drivers of sensitivity and resistance to Protein Arginine Methyltransferase 5 (PRMT5) inhibition, we perform a genome-wide CRISPR/Cas9 screen. We TP53 RNA-binding protein MUSASHI2 (MSI2) as the top-ranked sensitizer driver specific PRMT5i, GSK-591, respectively. deletion
Abstract Ongoing, first-in-human clinical trials illustrate the feasibility and translational potential of human pluripotent stem cell (hPSC)-based therapies in Parkinson’s disease (PD). However, a major unresolved challenge field is extensive death following transplantation with <10% grafted dopamine neurons surviving. Here, we performed pooled CRISPR/Cas9 screen to enhance survival postmitotic vivo . We identified p53-mediated apoptotic as contributor neuron loss uncovered causal link...