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Address: 2-439 BSB
Phone: (319) 384-4447
Mentor: Stefan Strack, PhD
Undergraduate Institution: Boise State University, BS
Year Entered Into Program: 2007 (MSTP) 2009 (PhD Program)
Mitochondria biogenesis requires fission of preexisting organelles by intracellular machinery. Similarly, mitochondrial transportation within a cell, fragmentation during apoptosis, and fission during mitosis also require the same intracellular machinery. The intracellular machinery that drive mitochondria fission consists of evolutionarily conserved mechanoenzymes and partner proteins. Among these mechanoenzymes is dynamin-related protein-1 (Drp1), a GTPase that is crucial for mitochondrial fission. A complex series of regulatory mechanisms are used to respond to the different cellular processes which require Drp1 driven mitochondrial fission. Our lab and others have demonstrated that the posttranslational activity of Drp1 is controlled by dynamic phosphorylation and dephosphorylation of specific serine residues. My work will focus on identifying novel regulatory posttranslational modification of Drp1. The Drp1 modifications will be characterized by investigating Drp1 recruitment to the mitochondria, binding to the mitochondria and mitochondrial fission. The biophysical mechanism of Drp1 driven fission will be explored. Finally, the role of Drp1 in ischemic injury models will be investigated. This work will utilize cell lines, primary tissue and whole animal models of ischemic injury and recovery.
Slupe, A., Williams, B., Larson, C., Lee, L.M., Primbs, T., Bruesch, A.J., Bjorklund, C., Warner, D.L., Peloquin, J., Shadle, S.E., Gambliel, H.A., Cusack, B.J., Olson, R.D., and Charlier, Jr, H.A.: Reduction of 13-Deoxydoxorubicin and Daunorubicinol Anthraquinones by Human Carbonyl Reductase. Cardiovascular Toxicology. 5(4):365-76, 2005. PMID: 16382174
Berhe, S., Slupe, A., Luster, C., Charlier, Jr., H.A.., Warner, D.L., Zalkow, L. H., Burgess, E.M., Enwerem, N.M., and Bakare, O.: Synthesis of 3-[(N-Carboalkoxy)ethylamino]-indazole-dione Derivatives and Their Biological Activities on Human Liver Carbonyl Reductase. Bioorg. Med. Chem. 18(1):134-41, 2010. PMCID: PMC2821159
Slupe, A., Merrill, R., Strack, S.: Determinants for Substrate Specificity of Protein Phosphatase 2A. Enzyme Res. 2011:398751, 2011. PMCID: PMC3132988
Wilson, T., Slupe, A., Strack, S.: Cell Signaling and Mitochondrial Dynamics: Implications for neuronal function and neurodegenerative disease. Neurobiol Dis. 51:13-26, 2013. PMCID: PMC3383441 [Available 2014/3/1]
Merrill R., Slupe A., Strack S.:N-terminal phosphorylation of protein phosphatase 2A/Bβ2 regulates translocation to mitochondria, dynamin-related protein 1 dephosphorylation, and neuronal survival. FEBS J. 280(2):662-673, 2013. PMCID: PMC3549015 [Available on 2014/1/1]
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