A5103042919- Spine and Intervertebral Disc Pathology
- Protein Degradation and Inhibitors
- Pluripotent Stem Cells Research
- Hippo pathway signaling and YAP/TAZ
- Genomics and Chromatin Dynamics
- Bacterial Genetics and Biotechnology
- DNA Repair Mechanisms
- Congenital heart defects research
- Ubiquitin and proteasome pathways
- RNA and protein synthesis mechanisms
- Advanced biosensing and bioanalysis techniques
- Multiple Myeloma Research and Treatments
- Cancer Mechanisms and Therapy
- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- interferon and immune responses
- Developmental Biology and Gene Regulation
- FOXO transcription factor regulation
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Renal and related cancers
- Microtubule and mitosis dynamics
City of Hope
2024
Beckman Research Institute
2024
Johns Hopkins University
2020
Johns Hopkins Medicine
2020
Virginia Commonwealth University
2014-2018
Abstract The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) its heterodimer partner ITGB5 β5) as essential α/β pair expansion. High-density gene tiling further pinpointed integral pocket within β-propeller domain αVβ5...
Epigenetic dysregulation has been reported in multiple cancers including leukemias. Nonetheless, the roles of epigenetic reader Tudor domains leukemia progression and therapy remain unexplored. Here, we conducted a domain–focused CRISPR screen identified SGF29, component SAGA/ATAC acetyltransferase complexes, as crucial factor for H3K9 acetylation, ribosomal gene expression, leukemogenesis. To facilitate drug development, integrated tiling scan with compound docking molecular dynamics...
Transcription factor Forkhead box protein M1b (FoxM1b) plays an important role during mitotic entry and progression. Our previous studies identified polo-like kinase 1 (PLK1) as a major regulator of FoxM1b. During G2/M transition, PLK1 directly interacts with phosphorylates FoxM1b, resulting in full activation the transactivation capacity Such vital regulatory mechanism is essential for timely However, molecular by which PLK1-mediated phosphorylation enhances transcriptional activity FoxM1b...
Accumulating evidence suggests participation of RNA-binding proteins with intrinsically disordered domains (IDPs) in the DNA damage response (DDR). These IDPs form liquid compartments at sites a poly(ADP ribose) (PAR)-dependent manner. However, it is greatly unknown how are involved DDR. We have shown previously that one RBM14 required for canonical nonhomologous end joining (cNHEJ). Here we show recruited to PARP- and RNA polymerase II (RNAPII)-dependent Both KU RNAPII-dependent generation...
Understanding how embryos specify asymmetric axes is a major focus of biology. While much has been done to discover signaling pathways and transcription factors important for axis specification, comparatively little known about epigenetic regulators are involved. Epigenetic operate downstream promote nuclear processes, most prominently transcription. To novel functions these complexes in establishment during early embryonic development, we characterized phenotypes mouse knockout (KO) allele...
Abstract Cell signaling pathways are enriched for biological processes crucial cellular communication, response to external stimuli, and metabolism. Here, a cell signaling‐focused CRISPR screen identified cytochrome c oxidase subunit 4 isoform 1 (COX4I1) as novel vulnerability in acute myeloid leukemia (AML). Depletion of COX4I1 hindered proliferation impacted vivo AML progression. Mechanistically, loss induced mitochondrial stress ferroptosis, disrupting ultrastructure oxidative...
Abstract Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in tumor microenvironment (TME). In culture, BPTF direct cytotoxicity receptor (NCR) mediated NK cytolytic to and human lines, demonstrating conserved functions. Blocking NCR1 vivo rescues KD weights, its importance for control of growth. We discovered occupies heparanase (Hpse)...