Andrew Slupe

Mentor: Stefan Strack, PhD

Year Entered Into Program: 2007 (MSTP) 2009 (PhD Program)

PhD Institution: University of Iowa, 2014 (MD, PhD)

Affiliations

  • Department of Pharmacology
  • Medical Scientist Training Program

Research Description

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. 

Publication(s)

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]  

Award(s)

  • NIMH MD/PhD Student Conf on Neuroscience and Psychiatry Travel Grant, 2008
  • Most Outstanding Entry, Gradute Student Poster Session, Carver College of Medicine, 2011
  • Recipient of Kirschstein NRSA Individual Predoctoral Fellowship, 2011-present
  • Most Outstanding Entry, Graduate Student Poster Session, Carver College of Medicine, 2012

Award(s) since graduating from the U of IA

  • Golden Rose Recipient, Oregon Health and Science University, 2014
  • FAER Resident Scholar, 2016
  • FAER Research Fellowship Grant (RFG 02-15-17 Slupe), 2017-present
  • OHSU Medical Research Foundation ECI Grant 2018-present
  • AUA Annual Meeting Invited Speaker and Travel Award, 2018
  • ASA Resident Research Essay Contest Winner, 2018

Research