Publications

We describe a new technique using yeast grown in continuous culture systems to assess the growth of yeast exposed to mutagen over a long (~3 week) period of time. Using these systems and a plate-based and whole genome sequencing-based assay, we were able to detect concentrations of the mutagens methyl methanesulfonate and ethidium bromide at concentrations 20x lower than the Ames test.

Yeast grown in continuous culture systems can detect mutagens with improved sensitivity relative to the Ames test. Joseph Y Ong, Julia T Pence, David C Molik, Heather AM Shepherd, Holly V Goodson. PLoS One. 2021 Mar 17;16(3):e0235303. doi: 10.1371/journal.pone.0235303.

E3 ubiquitin ligases regulate key aspects of cell growth, proliferation, and homeostasis. Consequently, their mutation or misregulation contributes to cancer initiation and progression. We review key ubiquitin ligases, their roles in cancer development, and current approaches toward targeting these proteins in cancer treatment.

E3 ubiquitin ligases in cancer and their pharmacological targeting. Joseph Y Ong, Jorge Z Torres. Book Chapter, Ubiquitin Proteasome System - Current Insights into Mechanism Cellular Regulation and Disease. IntechOpen. 2019 Feb 15. doi: 10.5772/intechopen.82883.

We developed a high-throughput chemical screen to identify small molecules that change the cell cycle profile of suspension cells. With this chemical screen, we identified leusin-1, a leukemia-specific inhibitor that arrests leukemia cells in G2-phase and induces apoptosis.

Leukemia cell cycle chemical profiling identifies the G2-phase leukemia specific inhibitor leusin-1. Xiaoyu Xia, Yu-Chen Lo, Ankur A Gholkar, Silvia Senese, Joseph Y Ong, Erick F Velasquez, Robert Damoiseaux, Jorge Z Torres. ACS Chem Biol. 2019 May 17;14(5):994-1001. doi: 10.1021/acschembio.9b00173.

Cell division is an intricately orchestrated process, and understanding the components of cell division and how they work together is an crucial aspect of understanding cell biology and human health. We review various genetic, chemical, proteomic, computational, and structural methodologies used to study cell division.

Dissecting the mechanisms of cell division. Joseph Y Ong, Jorge Z Torres. J Biol Chem. 2019 Jul 26;294(30):11382-11390. doi: 10.1074/jbc.AW119.008149.

Cell division is tightly regulated across space and time. Phase separation has recently emerged as a paradigm for explaining how macromolecules are regulated across many processes, including cell division. We review how phase separation has shaped our understanding of how proteins are organized, localized, and regulated during cell division.

Phase Separation in Cell Division. Joseph Y Ong, Jorge Z Torres. Mol Cell. 2020 Oct 1;80(1):9-20. doi: 10.1016/j.molcel.2020.08.007.

Phosphorylation, mediated by kinases and phosphatases, are one of the chief post-translational modifications in mitotic spindle assembly. We review the major phosphorylation events from G1 to metaphase that govern how the centrioles are duplicated, and how the centrosomes mature, are disjoined and separated, and form the bipolar spindle. We also discuss techniques used to study enzyme-substrate relationships and phosphorylation events in situ, within a cell.

Phospho-regulation of mitotic spindle assembly. Joseph Y Ong, Michelle C Bradley, Jorge Z Torres. Cytoskeleton (Hoboken). 2020 Dec;77(12):558-578. doi: 10.1002/cm.21649.

RNA-interference and CRISPR technology rely on identifying unique RNA/DNA sequences. Experiments using these technologies can be strengthened with rescue experiments using RNAi- or CRISPR-resistant sequences. I designed a free, easy-to-use web tool at jong2.pythonanywhere.com that takes an input DNA sequence and returns a different but synonymous DNA sequence, allowing for facile design of rescue DNA constructs.

Synonymous Mutation Generator: a web tool for designing RNAi-resistant sequences. Joseph Y. Ong. bioRxiv. 2021 Jan 4. doi: https://doi.org/10.1101/2021.01.02.425100.

Isoaspartate isomerization is a form of protein damage that generally accumulates over time. Here, we identified PCMTD1 as a Cul5 E3 ubiquitin ligase substrate adaptor. The N-terminus of PCMTD1 has motifs that are similar to those found in proteins that can bind isoaspartyl residues, and the C-terminus of PCMTD1 has motifs that allow it to bind to Cul5 and Elongins B/C. The existence of this PCMTD1-Cul5 complex suggests that PCMTD1 may be able to ubiquitylate and possibly degrade some damaged proteins containing iso-Asp residues within a cell.

Human Protein-l-isoaspartate O-Methyltransferase Domain-Containing Protein 1 (PCMTD1) Associates with Cullin-RING Ligase Proteins. Rebeccah A. Warmack, Eric Z. Pang, Esther Peluso, Jonathan D. Lowenson, Joseph Y. Ong, Jorge Z. Torres, Steven G. Clarke. Biochemistry. 2022 Apr 29. doi: 10.1021/acs.biochem.2c00130. PMID: 35486881