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Mentor: Stefan Strack, PhD
Year Entered Into Program: 2007 (MSTP) 2009 (PhD Program)
PhD Institution: University of Iowa, 2014 (MD, PhD)
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:
Slupe, A., Merrill, R., Strack,
S.: Determinants for Substrate Specificity of Protein Phosphatase 2A.
Enzyme Res. 2011:398751, 2011.PMCID:
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]
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
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