Aizenman Laboratory

Elias Aizenman, PhD

Elias Aizenman, PhD

Professor of Neurobiology
E-mail Website

Interests

Elias Aizenman was born and raised in Mexico City. He attended Boston University as an undergraduate, where he received training in neurobiology in the laboratory of Christopher Price, working on the retrograde axonal transport of free glycine in identified neurons of Aplysia. He also performed microbiological field work for Lynn Margulis in Laguna Figueroa, Baja California, Mexico. His graduate work was in toxicology at the Johns Hopkins University, where he studied the mechanism of anticholinesterase-induced generation of antidromic action potentials at the mouse neuromuscular junction with George Bierkamper and Elise Stanley. During his postdoctoral work with Stuart Lipton at Boston Children’s Hospital and Harvard Medical School, he discovered the redox modulatory site of the NMDA receptor in collaboration with Ralph Loring. With Paul Rosenberg, he demonstrated the oxidative conversion of L-DOPA to an excitotoxin. He began his independent career in the Department of Neurobiology at the University of Pittsburgh School of Medicine in 1989. In Pittsburgh, together with Ian Reynolds, Elias described the oxidative liberation of intracellular zinc as a critical component of neurotoxic cell signaling pathways. With Ed Levitan, he identified Kv2.1 as the channel responsible for the requisite loss of intracellular potassium during neuronal apoptosis.

Research in Elias’s laboratory is directed towards investigating cellular signaling processes leading to neuronal cell death. Cellular pathways leading to cell death are molecularly dissected in order to provide novel therapeutic targets to treat neurodegenerative disorders. This laboratory works on potential common final mediators of cell death signaling events that can be effectively targeted to treat neural disorders. This work is primarily focused on acute neuronal injury, such as stroke, although the results obtained from these studies have broader applications to more chronic/progressive neurodegenerative conditions. Over the last several years, the laboratory has investigated redox and photic regulation of NMDA receptors, excitotoxicity, dopamine oxidation pathways, zinc-mediated neurotoxicity, and Kv2.1 potassium channel facilitated forms of neuronal apoptosis, among other topics.

In addition to his position at Pitt, Elias also holds an adjunct appointment in the Department of Cell Biology and Physiology at Ben Gurion University of the Negev, in Beer Sheva, Israel.

Training

BS Biology Boston University 1981
PhD Toxicology Johns Hopkins University 1985
Post-doctoral Neuroscience Harvard Medical School 1985-1987

Positions Held

Instructor Harvard Medical School 1987-1989
Assistant Professor Harvard Medical School 1989
Assistant Professor University of Pittsburgh 1989-1994
Associate Professor University of Pittsburgh 1994-2001
Professor University of Pittsburgh 2001-
Adjunct Professor Ben Gurion University 2010-

Honors and awards

Summa Cum Laude with Distinction, Boston University (1981)
Phi Beta Kappa (1981)
Alumni Award in Biology, Boston University (1981)
NRSA in Developmental Neurology, Children’s Hospital and Harvard Medical School (1985-1987)
Research Fellowship, Fight for Sight (1985-1987)
BRRT Study Section, NIH (1994-1998)
Independent Investigator Award, NARSAD (1997)
Dozor Visiting Scholar, Ben Gurion University (2006)
President, International Society for Zinc Biology (2011-2013)
NOMD Study Section, NIH (2012-2018; Chair: 2017-2018)
William E. Brown Outstanding MSTP Mentor Award (2015)
Charles E. Kaufman New Initiative Award (2016; with Michael Palladino)
Dozor Visiting Scholar, Ben Gurion University (2017)
Dozor Visiting Scholar, Ben Gurion University (2020 - postponed due to Covid-19)
Philip Troen, MD, Excellence in Medical Student Research Mentoring Award (2021)

Gallery

Selected Publications

Liu HY, Gale JR, Reynolds IJ, Weiss JH, Aizenman E. The Multifaceted Roles of Zinc in Neuronal Mitochondrial Dysfunction. Biomedicines. 2021 Apr 29;9(5):489. doi: 10.3390/biomedicines9050489.

Krall RF, Tzounopoulos T, Aizenman E. The Function and Regulation of Zinc in the Brain. Neuroscience. 2021 Mar 1;457:235-258. doi: 10.1016/j.neuroscience.2021.01.010.

Yeh, C.; Schulien, A.; Molyneaux, B.; Aizenman, E. Lessons from Recent Advances in Ischemic Stroke Management and Targeting Kv2.1 for Neuroprotection. International Journal of Molecular Sciences. 2020 Aug 25;21(17):E6107. doi: 10.3390/ijms21176107.

Aizenman, E., R.H. Loring, I.J. Reynolds and P.A. Rosenberg. The redox biology of excitotoxic processes: the NMDA receptor, TOPA quinone, and the oxidative liberation of intracellular zinc. Frontiers in Neuroscience - Special Issue: Excitotoxicity Turns 50. 2020, 14:778, DOI: 10.3389/fnins.2020.00778.

Schulien, A.J., C.-Y Yeh, B.N. Orange, O.J. Pav, M.P. Hopkins, A. Moutal, R. Khanna, D. Sun, J.A. Justice* and E. Aizenman.* Targeted-disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels. Science Advances 01 Jul 2020: Vol. 6, no. 27, eaaz8110; DOI: 10.1126/sciadv.aaz8110 .

Krall, R.F., A. Moutal, M.B. Phillips, H. Asraf, J.W. Johnson, R. Khanna, M. Hershfinkel, E. Aizenman* and T. Tzounopoulos.* Synaptic zinc inhibition of NMDA receptors depends on the association of GluN2A with the zinc transporter ZnT1. Science Advances 03 Jul 2020: Vol. 6, no. 27, eabb1515; DOI: 10.1126/sciadv.abb1515

Aizenman E. Zinc signaling in the life and death of neurons. In: Zinc Signals in Cellular Functions and Disorders. Second Edition. Fukada, T. and T. Kambe, eds. Springer, January 2020, Chapter 9; pp. 165-185.

Yeh, C.-Y., Z. Ye, A. Moutal, S. Gaur, A.M. Henton, S. Kouvaros, J.L. Saloman, K.A. Hartnett-Scott, T. Tzounopoulos, R. Khanna, E. Aizenman* and C.J. Camacho.* Defining the Kv2.1-syntaxin interaction identifies a first-in-class small molecule neuroprotectant. Proceedings of the National Academy of Sciences (USA) 2019; 116:15696-15705.

Justice, J.A., D.T. Manjooran, C.-Y. Yeh, K.A. Hartnett-Scott, A.J. Schulien, G.J. Kosobucki, S. Mammen, M.J. Palladino and E. Aizenman. Molecular neuroprotection induced by zinc-dependent expression of hepatitis C-derived protein NS5A targeting Kv2.1 potassium channels. Journal of Pharmacology and Experimental Therapeutics 2018; 367:348-355.

Yeh, C.-Y., A.M. Bulas, A. Moutal, J.L. Saloman, K.A. Hartnett, C.T. Anderson, T. Tzounopoulos, D. Sun, R. Khanna and E. Aizenman. Targeting a potassium channel/syntaxin interaction ameliorates cell death in ischemic stroke. Journal of Neuroscience 2017; 37:5648-5658.

Justice, J.A., A.J. Schulien, K. He, K.A. Hartnett, E. Aizenman and N.H. Shah. Disruption of Kv2.1 somato-dendritic clusters prevents the apoptogenic increase of potassium currents. Neuroscience 2017; 354:158-167.

Schulien, A.J., J.A. Justice, R. Di Maio, Z.P. Wills, N.H. Shah and E. Aizenman. Zinc-induced calcium release via ryanodine receptors triggers calcineurin-dependent redistribution of cortical neuronal Kv2.1 K+ channels. Journal of Physiology 2016; 594:2647-2659.

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