Research in Dr. Aizenman’s laboratory is directed towards investigating cellular signaling processes leading to neuronal cell death and devising novel approaches to neuroprotection. Acute and chronic injurious processes in the brain lead to the activation of signaling cascades that eventually result in the demise of neurons. In Dr. Aizenman’s laboratory, cellular pathways leading to cell death are 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 could have broader applications to more chronic neurodegenerative conditions. The laboratory has investigated redox, photic and zinc regulation of NMDA receptors, excitotoxicity, dopamine oxidation pathways, zinc-mediated neurotoxicity, zinc signaling and epilepsy, and Kv2.1 potassium channel facilitated forms of neuronal apoptosis, among other topics.
The laboratory uses a wide range of techniques that include cellular electrophysiology, molecular biology, protein biochemistry, cell culture, cell imaging, gene-expression assays, toxicity assays, pharmacological screening and, in collaboration with Dr. Dandan Sun, in vivo ischemia models.
|PhD||Toxicology||Johns Hopkins University||1985|
|Post-doctoral||Neuroscience||Harvard Medical School||1985-1987|
|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)
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.
He, K., M.C. MCord, K.A. Hartnett and E. Aizenman. Regulation of pro-apoptotic phosphorylation of Kv2.1 K+ channels. PLoS One 2015; 10(6):e0129498.
McCord, M.C., P.H. Kullmann, K. He, K.A. Hartnett, J.P. Horn, I. Lotan and E. Aizenman. Syntaxin-binding domain of Kv2.1 is essential for the expression of apoptotic K+ currents. Journal of Physiology 2014; 592:3511-3521.
Shah, N.H., A.J. Schulien, K. Clemens, T.D. Aizenman, T.M. Hageman, Z.P. Wills and E. Aizenman. Cyclin E1 regulates Kv2.1 channel phospohorylation and localization in neuronal ischemia. Journal of Neuroscience 2014; 34:4326-4331.
McCord, M.C. and E. Aizenman. Convergent calcium and zinc signaling regulates apoptotic Kv2.1 potassium currents. Proceedings of the National Academy of Sciences (USA) 2013; 110:13988-13993.
Norris, C.A., K. He, M.G. Springer, K.A. Hartnett, J.P. Horn and E. Aizenman. Regulation of neuronal pro-apoptotic potassium currents by the hepatitis C virus non-structural protein 5A. Journal of Neuroscience 2012; 32:8865-70.
Kai He, PhD
Senior Research Scientistkai@pitt.edu
Diego Hernandez, MD, PhD