Research

My Current Research

I study the dynamic regulation of the chaperone protein Hsp70 by post-translational modifications (PTMs), collectively referred to as the Hsp70 Chaperone Code. Specifically, I look at how the 73 phosphorylation sites on Hsp70 individually affect a cell's ability to overcome metabolic stress. We like to think of this as a piano: just as each key makes a distinct sound, each PTM has a distinct role to play in cellular homeostasis.

Learn more about all of the research happening in the Truman Lab at UNC Charlotte by checking out the lab website!

Publications

Dissecting the Cdc37 Co-chaperone Code: Functional Roles in Chaperone-Mediated Stress AdaptationCdc37 is a kinase-specific co-chaperone that scaffolds protein kinase clients to the Hsp90 chaperone system. Although phosphorylation at residues S14 …

Novel insights into the post-translational modifications of Ydj1/DNAJA1 co-chaperonesThe activity of the Hsp70 molecular chaperone is regulated by a suite of helper co-chaperones that include J-proteins. Studies on J-proteins have hist…

Acetylation of the yeast Hsp40 chaperone protein Ydj1 fine-tunes proteostasis and translational fidelityAuthor summary Cells require a suite of chaperone and co-chaperone proteins to maintain a healthy balance of functional proteins. A large number of modifications on chaperone and co-chaperone proteins have been identified, but their functional importance has not been fully explored. In this study, we identify acetylation sites on the yeast co-chaperone Ydj1 that impact its interactions with major chaperones and client proteins including those involved in protein synthesis. This work sheds light on how modifications on co-chaperones can also play an important role in the health of the proteome.

The APE2 Exonuclease Is a Client of the Hsp70–Hsp90 Axis in Yeast and Mammalian CellsMolecular chaperones such as Hsp70 and Hsp90 help fold and activate proteins in important signal transduction pathways that include DNA damage response (DDR). Previous studies have suggested that the levels of the mammalian APE2 exonuclease, a protein critical for DNA repair, may be dependent on chaperone activity. In this study, we demonstrate that the budding yeast Apn2 exonuclease interacts with molecular chaperones Ssa1 and Hsp82 and the co-chaperone Ydj1. Although Apn2 does not display a binding preference for any specific cytosolic Hsp70 or Hsp90 paralog, Ssa1 is unable to support Apn2 stability when present as the sole Ssa in the cell. Demonstrating conservation of this mechanism, the exonuclease APE2 also binds to Hsp70 and Hsp90 in mammalian cells. Inhibition of chaperone function via specific small molecule inhibitors results in a rapid loss of APE2 in a range of cancer cell lines. Taken together, these data identify APE2 and Apn2 as clients of the chaperone system in yeast and mammalian cells and suggest that chaperone inhibition may form the basis of novel anticancer therapies that target APE2-mediated processes.