Research

Environmental cues such as heat shock, UV irradiation, hypoxia, and oxidative stress initiate many eukaryotic cellular responses, including protective responses to ensure their survival. One of the most rapid of these responses is to prevent mRNA translation to into protein to allow cells to adapt to stress. This stalled mRNA is sequestered to specific cytosolic compartments known as stress granule. Stress granules represent a complex assemblage of translational initiation factors, proteins involved in translational control, the microtubule array, and chaperone proteins such as G3BP-1 (Ras-GTPase-activating protein Src homology 3 domain-binding protein-1). We have shown that MK-STYX binds G3BP-1 and inhibit stress granule formation. However, how MK-STYX accomplishes this inhibition is unclear. Thus, we seek to elucidate the mechanism required by MK-STYX to inhibit stress granule formation? Understanding this mechanism will proved insight into the role MK-STYX plays as a regulator of mRNA stability and in the dynamics of stress granule formation.

The role of the MAPK (Mitogen-activated protein kinase) signal pathway in neuronal development has received increasing attention in the past several years. Environmental stimuli such as neurotrophins, growth signals, and stress activate receptor tyrosine kinases that are responsible for initiating the phosphorylation cascade required to trigger the MAPK cascade. MAPKs are abundantly expressed in neurons in the central nervous system, thus it is not surprising that a malfunction in this signaling cascade would lead to neurological disorders. Intriguingly, some neurological disorders are caused by hyperphosphorylation, whereas others are caused by the inhibition of MAPK phosphorylation. Despite compelling evidence that MAPKs are significant regulators in neuronal development, how the MAPK signaling pathway is maintained and modulated remains elusive. My lab investigates the role the pseudophosphatase MK-STYX plays in neuronal development.

Although the critical cysteine required for phosphatase activity is missing in MK-STYX, MK-STYX still binds targeted proteins such as G3BP-1. Many pseuodophosphatases such as the myotubularins have been shown to interact with their active homologs creating psuedophosphatase:phosphatase interactions. MK-STYX is not only a pseudophosphatase, but also consists of a rhodanese domain that may serve as a docking domain for proteins such as MAPKs. Understanding the MK-STYX’s protein interactions may lead to the functional importance of pseudophosphatases. My lab will begin to identify interesting binding partners of MK-STYX through proteomics. Several cytoskeleton interacting partners of MK-STYX have been identified. My research program is investigating these interactions thought fluoresces microscopy, cellular and molecular biology, biochemistry, and proteomics.

For over a decade, the focus of my lab has been on understanding MK-STYX as a signaling regulator. The interests of MK-STYX remains and continues to be pursued. We have had significant findings with this pseudophosphatase and are ready to expand to other pseudophosphatases such as STYXL2 and the catalytically in active members of tensin. Our studies with MK-STYX serve as a foundational template along with new innovative technology to investigate. Investigating these new pseudophosphaases are a great way to provide undergraduates and Master’s student with an independent research program.