Education and Training
B.A. in Biology, Cornell University, Ithaca, NY
Ph.D. in Neuroscience, University of Maryland, Baltimore
Postdoctoral Fellowship, John Hopkins University, Baltimore, MD
Staff Scientist, The Buck Institute for Age Research, Novato, CA
Dr. Polster's laboratory studies basic subcellular mechanisms that govern neuroinflammation and cell death following brain injury, with an emphasis on mitochondrial permeabilization and bioenergetic dysfunction. Past investigations have centered on control of mitochondrial integrity and quality by Bcl-2 family proteins and Drp1. Recent and active projects extend these interests to study the role of mitochondrial structural and functional remodeling in pro-inflammatory microglial activation, how microglial activation exacerbates neuronal injury, and translational strategies for targeting immunometabolism to promote brain recovery.
The lab employs a variety of research approaches, including in vitro and in vivo models related to traumatic brain injury and hypoxic-ischemic encephalopathy. Patient-derived human neurodegenerative disease cell models are also being explored. The lab has been a leader in implementing the Seahorse Extracellular Flux Analyzer in unique ways for the study of mitochondrial dysfunction in live cells and tissues, including the first measurements from organotypic hippocampal slices and a novel assay for detecting the release of the cell death-inducing mitochondrial protein cytochrome c in live cells. Among many techniques, live and fixed-cell fluorescence microscopy are being used to investigate multiple aspects of mitochondrial structure and function in neural cells, including studies done at various physiological and pathological brain oxygen levels that are well below those present in the atmosphere.
mitochondria, mitochondrial fission, bioenergetics, oxygen, respiration, Seahorse, reactive oxygen species, superoxide, apoptosis, cytochrome c, AIF, Bax, Bcl-2, Drp1, calpain, neurons, glutamate excitotoxicity, nitric oxide, astrocytes, microglia, neuroinflammation, neurodegeneration, traumatic brain injury, neonatal hypoxic-ischemic encephalopathy, idebenone, mdivi-1
Bordt EA, Polster BM. NADPH oxidase- and mitochondria-derived reactive oxygen species in proinflammatory microglial activation: a bipartisan affair? Free Radic Biol Med. 2014 Nov;76:34-46. PubMed PMID: 25091898.
Bordt, EA, Clerc, P, Roelofs, BA, Saladino, AJ, Tretter, L, Adam-Vizi, V, Cherok, E, Khalil, A, Yadava, N, Ge, SX, Francis, TC, Kennedy, NW, Picton, LK, Kumar, T, Uppuluri, S, Miller, AM, Itoh, K, Karbowski, M, Sesaki, H, Hill, RB, Polster, BM. The Putative Drp1 Inhibitor mdivi-1 is a Reversible Complex I Inhibitor that Modulates Reactive Oxygen Species. Dev Cell. 2017 Mar; 40(6):583-594. PubMed PMID: 28350990.
Jaber, SM, Bordt, EA, Bhatt, NM, Lewis, DM, Gerecht, S, Fiskum, G, Polster, BM. Sex differences in the mitochondrial bioenergetics of astrocytes but not microglia at a physiologically relevant brain oxygen tension. Neurochem Int 2018;117:82-90. PubMed PMID: 28888963.
Jaber SM, Yadava N, Polster BM. Mapping Mitochondrial Respiratory Chain Deficiencies by Respirometry: Beyond the Mito Stress Test. Exp Neurol. 2020 Jun; 328:113282. PubMed PMID: 32165258.
Jaber, SM, Ge, SX, Milstein, JL, VanRyzin, JW, Waddell, J, Polster, BM. Idebenone has distinct effects on mitochondrial respiration in cortical astrocytes compared to cortical neurons due to differential NQO1 activity. J Neurosci. 2020 Jun 3; 40(23):4609-4619. PubMed PMID: 32350039.
Polster BM, Kinnally, KW, Fiskum G. BH3 Domain Peptide Induces Cell Type-Selective Mitochondrial Outer Membrane Permeability. J Biol Chem. 2001; 276, 37887-94. PubMed PMID: 11483608.
Hardwick JM, Polster BM. Bax, along with lipid conspirators, allows cytochrome c to escape mitochondria. Mol Cell. 2002 Nov;10(5):963-5. PubMed PMID: 12453403.
Polster BM, Robertson CL, Bucci CJ, Suzuki M, Fiskum G. Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c. Cell Death Differ. 2003 Mar;10(3):365-70. PubMed PMID: 12700636.
Polster BM, Basañez G, Young M, Suzuki M, Fiskum G. Inhibition of Bax-induced cytochrome c release from neural cell and brain mitochondria by dibucaine and propranolol. J Neurosci. 2003 Apr 1;23(7):2735-43. PubMed PMID: 12684459.
Polster BM*, Basañez G, Etxebarria A, Hardwick JM, Nicholls DG. Calpain I induces cleavage and release of apoptosis-inducing factor from isolated mitochondria. J Biol Chem. 2005 Feb 25;280(8):6447-54. PubMed PMID: 15590628. *corresponding author
Chinta SJ, Rane A, Yadava N, Andersen JK, Nicholls DG, Polster BM. Reactive oxygen species regulation by AIF- and complex I-depleted brain mitochondria. Free Radic Biol Med. 2009 Apr 1;46(7):939-47. PubMed PMID: 19280713.
Gerencser AA, Mark KA, Hubbard AE, Divakaruni AS, Mehrabian Z, Nicholls DG, Polster BM. Real-time visualization of cytoplasmic calpain activation and calcium deregulation in acute glutamate excitotoxicity. J Neurochem. 2009 Aug;110(3):990-1004. PubMed PMID: 19493161.
Schuh RA, Clerc P, Hwang H, Mehrabian Z, Bittman K, Chen H, Polster BM. Adaptation of microplate-based respirometry for hippocampal slices and analysis of respiratory capacity. J Neurosci Res. 2011 Dec;89(12):1979-88. PubMed PMID: 21520220.
Clerc P, Carey GB, Mehrabian Z, Wei M, Hwang H, Girnun GD, Chen H, Martin SS, Polster BM. Rapid detection of an ABT-737-sensitive primed for death state in cells using microplate-based respirometry. PLoS One. 2012;7(8):e42487. PubMed PMID: 22880001.
Clerc P, Polster BM. Investigation of mitochondrial dysfunction by sequential microplate-based respiration measurements from intact and permeabilized neurons. PLoS One. 2012; 7(4):e34465. PubMed PMID: 22496810.
Polster BM, Nicholls DG, Ge SX, Roelofs BA. Use of potentiometric fluorophores in the measurement of mitochondrial reactive oxygen species. Methods Enzymol. 2014; 547:225-50. PubMed PMID: 25416361.
Clerc P, Ge SX, Hwang H, Waddell J, Roelofs BA, Karbowski M, Sesaki H, Polster BM. Drp1 is Dispensable for Apoptotic Cytochrome c Release in Primed MCF10A and Fibroblast Cells but Affects Bcl-2 Antagonist-induced Respiratory Changes. Br J Pharmacol. 2014; 171(8), 1988-99. PMID: 24206264.
Complete List of Published Work in My Bibliography:
Member, Society for Neuroscience, 2000-present
Neurochemistry International Editorial Board, 2012-2021
Certificate of Excellence in Reviewing, Elsevier in Conjunction with Neurochemistry International, 2013
Member, Society for Redox Biology and Medicine, 2015-present
Graduate Program in Life Sciences (GPILS) Teacher of the Year, University of Maryland, Baltimore, 2018
Member, Association of University Anesthesiologists, 2019-present
Current Research Support
Reprogramming proinflammatory microglia by restoring mitochondrial function
NIH/NINDS R01 NS112212
Targeting mitochondrial Complex I in neonatal hypoxia-ischemia
NIH/NINDS R01 NS122777
Completed Research Support (Recent)
Novel mechanisms of microglial neurotoxicity at physiological oxygen
NIH/NINDS R01 NS085165
Mitochondrial structural and functional remodeling in microglial activation
NIH/NINDS R21 NS096538
- Primary cortical neuron, astrocyte, and microglia cell culture
- Microglia-like cells differentiated from human peripheral blood mononuclear cells
- Real-time measurement of cellular oxygen consumption and glycolysis rates (Seahorse XF24/96, Resipher)
- Live-cell fluorescent imaging of:
- mitochondrial membrane potential (e.g., using TMRM)
- reactive oxygen species (e.g., using dihydroethidium)
- intracellular calcium changes (e.g., using fluo indicators)
- mitochondrial remodeling (e.g., using mito-YFP)
- Fluorescence-based cell death assays (e.g., propidium iodide, Annexin V, Yo-Pro-1)
- Isolated mitochondria assays, including measurements of membrane potential, calcium uptake, oxygen consumption, and reactive oxygen species generation
- Enzyme assays, western blot, ELISA, biochemistry techniques, immunocytochemistry