Panayotis Vacratsis, Ph.D.
Dept. of Chemistry & Biochemistry
University of Windsor
My laboratory is a multidisciplinary research group that integrates mass spectrometry and cell biology techniques to discover and investigate novel enzymes predicted to be critical regulators of fundamental cellular processes such as cell growth, cell survival, cancer progression, and neuromuscular biology. Recently, we have elucidated novel biological roles for two poorly characterized phosphatases:
Current projects include:
I. Functional characterization of hYVH1: a unique dual specificity phosphatase overexpressed in late stage cancers.
Our laboratory has recently discovered that the evolutionary conserved dual specificity phosphatase hYVH1 (also known as DUSP12) is a potent cell survival enzyme. Furthermore, we have recently determined that its expression regulates cell cycle progression. Human YVH1 is widely expressed in human tissues and its gene has been found amplified in a wide variety of late stage malignancies. Our results showing that hYVH1 can function as a regulator of cellular proliferation and as an anti-apoptotic factor (cell survival) coupled with the gene amplification findings, tempts us to speculate that overexpression of the hyvh1 gene will impart on tumour cells the ability to survive unfavourable microenvironments and support metastasis.
II. Molecular mechanisms regulating the myotubularin lipid phosphatase MTMR2 mutated in the neuromuscular disorder Charcot-Marie Tooth disease.
Mutations in the MTMR2 gene has been shown to cause CMT4B1, a demyelinating neuropathy characterized by abnormally folded myelin sheaths causing inadequate nerve conduction to the muscles eventually leading to muscle weakness and atrophy. CMT is the most common neuromuscular disorder with an affliction rate of 1:2000. MTMR2 has also been shown to be a cell survival phosphatase that induces cell proliferation. We have recently discovered a sophisticated mechanism explaining how MTMR2 finds its physiological substrate. Our data indicates that phosphorylation (a chemical tag) keeps MTMR2 away from its lipid substrates and the presence of this tag is controlled by factors that stimulate cell growth, proliferation, and activate myelination. We have also identified a new MTMR2 target (RME8) which may be over active in CMT4B1 and thus represents a potential therapeutic target for this neuromuscular disorder.
Recent Selected Publications
Kozarova A, Hudson JW, Vacratsis PO. (2011) The Dual Specificity Phosphatase hYVH1 (DUSP12) is a Novel Modular of Cellular DNA Content. Cell Cycle., 10, 1669-78
Franklin NE, Taylor GS, Vacratsis PO. (2011) Endosomal Targeting of the Phosphoinositide 3-Phosphatase MTMR2 is Regulated by an N-Terminal Phosphorylation site. J Biol Chem, 286, 15841-53
Xhabija B, Taylor GS, Fujibayashi A, Sekiguchi K, Vacratsis PO. (2011) Receptor mediated endocytosis 8 is a novel PI(3)P Binding Protein Regulated by MTMR2. FEBS Letters., 585, 1722-8
Faccenda A, Bonham CA, Vacratsis PO, Zhang X, Mutus B. (2010) Gold Nanoparticle Enrichment Method for Identifying S-Nitrosylation and S-Glutathionylation Sites in Proteins. J Am Chem Soc., 132, 11392-4
Bonham CA, Vacratsis PO. (2009) Redox regulation of the dual specificity phosphatase hYVH1 through disulfide bond formation. J Biol Chem., 284, 22853-64
Sharda PR, Bonham CA, Mucaki EJ, Butt Z, Vacratsis PO. (2009) The dual-specificity phosphatase hYVH1 interacts with Hsp70 and prevents heat-shock-induced cell death. Biochem J. 418, 391-401.