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Personal History
Education/Training* B.A. in Biology, Cornell University, Ithaca, NY
* Ph.D. in Neuroscience, University of Maryland, Baltimore
* Postdoctoral Fellowship, Cell Death, John Hopkins University, Baltimore, MD
* Staff Scientist, Mechanisms of Neurodegeneration, The Buck Institute for Age Research, Novato, CA
Research Interests
Limiting damage to mitochondria, the primary energy-generating organelles of the cell, is crucial for neuroprotection. My research focuses on understanding the basic subcellular mechanisms that govern neural cell death and survival in neurodegenerative disorders. My investigations center on two key pathways of injury, apoptotic programmed cell death and excitotoxic cell death initiated by excess release of the neurotransmitter glutamate. Current objectives include 1) unraveling how mitochondrial protease activities contribute to bioenergetic dysfunction and reactive oxygen species production, 2) elucidating the roles and targets of calcium-dependent calpain proteases in neurotoxicity, and 3) improving our understanding of the roles that multi-functional apoptosis-related proteins such as Bax, AIF, and Htra2/Omi play in mitochondrial maintenance and injury.Lab Techniques and Equipment
Live-cell fluorescent imaging of:* mitochondrial membrane potential (TMRM)
* reactive oxygen species (Dihydroethidium and MitoSOX Red)
* intracellular calcium changes (Fluo indicators)
* intracellular protease activation (custom-designed cell permeable fluorescence resonance energy transfer (FRET)-based probes)
Fluorescence-based cell death assays (propidium iodide, Yo-Pro-1)
Real-time measurement of cellular oxygen consumption and glycolysis rates using an XF24 Analyzer (Seahorse Biosciences)
Measurements of membrane potential, calcium uptake, oxygen consumption, and reactive oxygen species generation with isolated mitochondria
Standard protein biochemistry and fixed cell imaging
Publications
Journal Articles
Kushnareva, Y. E., Polster, B. M., Sokolove, P. M., Kinnally, K. W., and Fiskum, G. (2001) Mitochondrial precursor signal peptide induces a unique permeability transition and release of cytochrome c from liver and brain mitochondria. Arch Biochem Biophys 386: 251-260.
Polster, B.M., Kinnally, K.W., and Fiskum, G. (2001) BH3 domain peptide induces cell type-selective mitochondrial outer membrane permeability. J Biol Chem 276: 37887-94.
Starkov, A.A., Polster, B.M., and Fiskum, G. (2002) Regulation of hydrogen peroxide production by brain mitochondria by calcium and Bax. J Neurochem 83: 220-8.
Hardwick, J.M. and Polster, B.M. (2002) Bax, along with lipid conspirators, allows cytochrome c to escape mitochondria. Mol Cell 10: 963-5.
Fiskum, G., Starkov, A., Polster, B.M., Chinopoulous, C. (2003) Mitochondrial mechanisms of neural cell death and neuroprotective interventions in Parkinson' Disease. Ann NY Acad Sci 991: 111-9.
Polster, B.M., Robertson, C.L., Bucci, C.J., Suzuki, M., and Fiskum, G. (2003) Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release. Cell Death Differ 10: 365-70.
Polster, B.M., Basanez, G., Young, M., Suzuki, M., and Fiskum, G. (2003) Inhibition of Bax-induced cytochrome c release from neural cell and brain mitochondria by dibucaine and propranolol. J Neurosci 23: 2735-43.
Jonas, E. A., Hoit, D., Hickman, J.A., Brandt, T.A., Polster, B.M., Fannjiang, Y., McCarthy, E., Montanez, M.K., Hardwick, J.M., Kaczmarek, L.K. (2003) Modulation of synaptic transmission by the BCL-2 family protein BCL-xL. J Neurosci 23:8423-31.
Jonas, E.A., Hickman, J.A., Chachar, M., Polster, B.M., Brandt, T.A., Fannjiang, Y., Ivanovska, I., Basanez, G., Kinnally, K.W., Zimmerberg, J., Hardwick, J.M., and Kaczmarek, L.K. (2004) Proapoptotic N-truncated BCL-xL protein activates endogenous mitochondrial channels in living synaptic terminals. Proc Nat Acad Sci 101: 13590-5.
Polster, B.M. and Fiskum, G. (2004) Mitochondrial mechanisms of neural cell apoptosis. J Neurochem 90: 1281-9.
Polster, B.M., Pevsner, J. and Hardwick, J.M. (2004) Viral homologs of Bcl-2 and their role in virus replication and associated diseases. Biochimica et Biophysica Acta 1644: 211-27.
Polster, B.M., Basanez, G., Etxebarria A., Hardwick, J.M., and Nicholls, G. (2005) Calpain I induces cleavage and release of apoptosis inducing factor from isolated mitochondria. J Biol Chem 280: 6447-54.
Bonanni, L., Chachar, M., Jover T., Li, H., Jones, A., Yakota, H., Ofengeim, D., Miyawaki, T., Cho, C.H., Polster, B.M., Pypaert, M., Hardwick, J.M., Sensi, S.L., Zukin, R.S., and Jonas, E.A. (2006) Zinc-dependent multiconductance channel activity in mitochondria isolated from ischemic brain. J Neurosci 26: 6851-62.
Johnson-Cadwell, L.I., Jekabsons, M.B., Wang, A., Polster, B.M., and Nicholls, D.G. (2007) Mild uncoupling does not decrease mitochondrial superoxide levels in cultured cerebellar granule neurons but decreases spare respiratory capacity and increases toxicity to glutamate and oxidative stress. J Neurochem 101: 1619-31.
Polster, B.M., Arze, R., Lyttle, M.H., Nicholls, D.G., and Hudson, D. (2007) Solid phase synthesis of dual labeled peptides: development of cell permeable calpain specific substrates. Intl J of Peptide Res and Therapeutics 13: 83-91.
Chinta, S.J., Rane, A., Yadava, N., Andersen, J.K., Nicholls, D.G., and Polster, B.M. (2009) Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria. Free Radical Biology & Medicine 46: 939-47.
Gerencser, A.A., Mark, K.A., Hubbard, A.E., Divakaruni, A.S., Mehrabian, Z., Nicholls, D.G., and Polster, B.M. (2009) Real-time visualization of cytoplasmic calpain activation and calcium deregulation in acute glutamate excitotoxicity. J Neurochem 110: 990-1004.
Book Chapters
Fiskum, G., Polster, B.M., and Kowaltowski, A.J. (2000) Mitochondria as targets of neuroprotection by Bcl-2 family proteins. J. Krieglstein, S. Klumpp (Eds.) Pharmacology of Cerebral Ischemia 2000, 177-188.