Alexander M. Dizhoor

Professor, Pennsylvania College of Optometry


 adizhoor@salus.edu
 

Education:

  • PhD Molecular Biology, Moscow University, 1985

Role At Salus University:

  • Hafter Chair in Pharmacology

Selected representative publications:

  •  Jacobson SG, Cideciyan AV, Peshenko IV, Sumaroka A, Olshevskaya EV, Schwartz SB, Roman AJ, Olivares MB, Sadigh S, Heon E, Stone EM, Dizhoor AM (2013) Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone photoreceptor vision correlates with biochemical properties of the mutants. Human Molecular Genetics 22 (1): 168-183
  • Peshenko IV, Olshevskaya EV, Lim S, Ames JB, Dizhoor AM (2014) Identification of Target Binding Site in Photoreceptor Guanylyl Cyclase Activating Protein 1 (GCAP1). J Biol Chem. 289, 10140–10154
  • Dizhoor, A.M., Chen, Ch.-K., Olshevskaya, E., Sinelnikova, V.V., Philippov, P.P., Hurley, J.B. Role of the acylated amino - terminus of recovering in Ca - dependent; membrane interaction. Science 259, 829-832 (1993)
  • Dizhoor, A.M., Lowe, D.G., Olshevskaya, E.V., Laura, R.P.,  Hurley, J.B.  The human photoreceptor membrane guanylyl cyclase, RetGC, is present in outer segments and is regulated by calcium and a soluble activator. Neuron  12, 1345-1352 (1994) 
  • Lowe, D.G., Dizhoor, A.M., Liu, K., Gu, O., Spencer, M., Laura, R., Lu, L., Hurley. J.B.Cloning and expression of a second photoreceptor - specific membrane guanylyl cyclase (RetGC), RetGC-2. Proc. Natl. Acad. Sci. U.S.A.. 92, 5535-5539 (1995) 
  • Dizhoor, A.M., Olshevskaya, E.V., Henzel, W.J., Wong, S., Stults, J.T., Ankoudinova, I., Hurley, J.B. Cloning, sequencing and expression of a 24 kDa Ca2+-binding protein activating photoreceptor guanylyl cyclase. J. Biol. Chem.  270,  25200-25206 (1995) 
  • Dizhoor A.M., Boikov, S.G., Olshevskaya, E.V. Constitutive Activation of Photoreceptor Guanylate Cyclase By Y99C Mutant of GCAP-1: Possible Role In Causing Human Autosomal Dominant Cone Degeneration. J. Biol. Chem. 273, 17311–17314 (1998). 
  • Olshevskaya, E.V., Boikov, S., Ermilov, A., Krylov, D., Hurley, J.B., Dizhoor, A.M.  Mapping functional domains of the guanylate cyclase regulator protein, GCAP-2. J. Biol. Chem. 274, 10823-10832 (1999).
  • Ermilov AN, Olshevskaya EV, Dizhoor, A.M. Instead of binding calcium, one of the EF-hand structures in guanylyl cyclase activating protein-2 is required for targeting photoreceptor guanylyl cyclase.J Biol Chem. 276(51):48143-8 (2001)
  • Peshenko, I.V., Dizhoor, A.M. Guanylyl Cyclase Activating Proteins (GCAPs) Are Ca2+/Mg2+-Sensors: Implications for Photoreceptor Guanylyl Cyclase (RetGC) Regulation in vitro and in vivo. Journal of  Biological Chemistry 279: 16903-16906 (2004)
  • Olshevskaya, E.V., Calvert P.D., Woodruff, M.L., Peshenko  I.V., Savchenko A.B.., Makino  C.L., Ho Y-S., Fain G.L., Dizhoor, A.M. The Y99C mutation in guanylyl cyclase activating protein 1 (GCAP1) increases intracellular Ca2+ and causes photoreceptor degeneration in transgenic mice. Journal of Neuroscience 24, 6078-6085 (2004)
  • Bi, A., Cui, J., Ma, Y.-P., Olshevskaya, E., Pu, M., Dizhoor, A.M., Pan, Z.-H. (2006) Ectopic Expression of a microbial-type rhodopsin restores visual response in mice with photoreceptor degeneration.  Neuron 50, 1-11 (2006)
  • Peshenko, I.V., Dizhoor, A.M. Ca2+- And Mg2+-Binding Properties Of GCAP-1: Evidence That Mg2+-Bound Form Is The Physiological Activator Of Photoreceptor Guanylyl Cyclase. J. Biol. Chem. 281: 23830-23841 (2006)
  • Peshenko IV, Dizhoor A.M. Activation and inhibition of photoreceptor guanylyl cyclase by guanylyl cyclase activating protein 1 (GCAP-1): the functional role of Mg2+/Ca2+ exchange in EF-hand domains. J. Biol. Chem. 282:21645-52 (2007)
  • Woodruff ML, Olshevskaya EV, Savchenko AB, Peshenko IV, Barrett R, Bush RA, Sieving PA, Fain GL, Dizhoor AM. Constitutive excitation by Gly90Asp rhodopsin rescues rods from degeneration caused by elevated production of cGMP in the dark.  Journal of Neuroscience 27:8805-15 (2007)
  • Peshenko, I.V., Olshevskaya, E.V., Dizhoor, A.M. (2008) Binding of guanylyl cyclase activating protein 1 (GCAP1) to retinal guanylyl cyclase (RetGC1): The role of individual EF-hands. J. Biol. Chem. 283, 21747-57
  • Makino, C.L, Peshenko, I.V., Wen X-H., Elena V. Olshevskaya, E.V., Barrett, R, Dizhoor, A.M. (2008) A Role for GCAP2 in Regulating the Photoresponse: Guanylyl Cyclase Activation and Rod Electrophysiology in GUCA1B Knockout Mice. J. Biol. Chem. 283, 29135-43
  • Dizhoor, A.M. Woodruff, M.L, Olshevskaya, E.V, Cilluffo M.C, Carter Cornwall, M., Sieving, P.A, and Fain, G.L. (2008) Night blindness and the mechanism of constitutive signaling of mutant G90D rhodopsin. Journal of Neuroscience 28, 11662-72.

Professional Activities/Recognition/Awards:

Societies & Organizations:

  • ARVO, Society for Neuroscience,  American Society for Biochemistry and Molecular Biology
  • NIH CSR/BDPE Study Section, permanent member, 2005–2010.
  • NIH CSR/ZRG1 CB-G;  -C, MIST study sections, ad hoc reviewer 2011–2012.

Recognition:

  • Research Excellence Award, Wayne State University, 2001
  • Hafter Chair in Pharmacology, PCO, 2002

Awards:

  • Human Frontier Science Program Organization, 1992-1994;
  • National Institutes of Health R01, 1996-present;
  • Research to Prevent Blindness Career Development Award 1997-2001;
  • Lions of Pennsylvania Sight Preservation, 2003;
  • Pennsylvania Department of Health, Formula/CURE grants 2003-present

Research Activities:

  1. Study of  signal transduction in the retina
  2. Molecular mechanisms of congenital retinal degeneration
  3. Gene therapy approaches to sight restoration