Dr. Gordon W. Glazner

Gordon W. Glazner, Ph.D.
Associate Professor - Department of Pharmacology and Therapeutics
University of Manitoba
Principal Investigator - Division of Neurodegenerative Disorders
St. Boniface Hospital Research Centre
R4052-351 Tache Avenue, Winnipeg, MB R2H 2A6
tel: (204) 235-3943; fax: (204) 237-4092
Email:   gglazner@sbrc.ca  

Research Focus:

Our laboratory has recently discovered a new regulation system in neurons that is related to the pathology of Alzheimers and stroke. We have found that under certain kinds of stress, like those found in neurological disease, a whole group of proteins are destroyed. This protein degradation is controlled by the movement of calcium inside the neuron, which for many years has been known to play a part in the death of the cells, but nobody has ever been able to determine why. Working with Dr. Kathleen Binns and Keith Ashman at the University of Toronto, we have identified these proteins, and found them to be a collection of enzymes that are critical to the survival and normal functioning of the neurons. This work likely has major implications outside of neuroscience, since this pathway is seen in other cells as well.

This new breakthrough has attracted major international attention. Dr. Alexi Verkhratsky, a world-renowned professor and Head of Neuroscience at the University of Manchester, and editor of the journal Cell Calcium, has agreed to come to St. Boniface Hospital Research Centre for a month this spring to focus on this discovery. Dr. Verkhratsky and I will also be investigating how amyloid beta peptide, the major component of senile plaques in AD, causes movement of calcium in neurons, and whether this new protein degradation pathway is a key to neuronal death.

I have been invited to present these findings to two groups in Japan, the RIKEN Institute in Tokyo and the University of Ozaki, where I will be hosted this spring by leading scientists in the field of calcium regulation. In addition, I have been invited to be a speaker at the annual IBRO conference in Prague, Czech Republic in summer. I am in the process of forming an international research group focused on intracellular calcium and neuronal death. This group will be composed of select scientists from England, the US, Japan and Canada, and is planning to meet this fall to formalize research plans.

In the last 2 years, I have received two national awards and two provincial grants. Last year, my grant on the role of intracellular calcium and inherited Alzheimer disease was chosen as only one of two in the nation to be an AstraZenica/CIHR/Alzheimers award, and was ranked as the top biomedical grant in the nationwide competition, a first for Manitoba. For this, I was invited to be the Manitoba representative in the formation of a Canada-wide AD research group. In addition, I was awarded a CIHR operating grant to examine the role of intracellular calcium and ER-regulated transcription factors in peripheral neuropathy, a major complication in diabetes.

Also last year, I was awarded a $500,000 Canadian Foundation for Innovation grant to build a unique microscope which combines the power of lasers for imaging, and robotic control of the microscope itself. This is the first microscope of its kind in Canada, and one of only a handful in all of North America. Because of its distinctive qualities, this microscope has attracted international collaborations with leading scientists.

Shortly after I began working at UM, I secured venture capital from Keystone Investment of $1 million to form 2 biotechnology companies based upon a novel approach to treating cancer and HIV infection using inhibitors of cellular calcium movement. The compound being studied is currently under investigation has shown very potent killing effects on aggressive cancers, with very little toxicity to normal cells. This drug will soon be tested in animals for toxicity and the ability to kill currently untreatable tumors.

Key Publications:
 

A. Published or in press refereed papers

1. Smith D, Tweed C, Fernyhough P, Glazner G* (2009). Activation of NF-kappaB in Axons and Schwann cells at Site of Sciatic Nerve Crush and Role in Modulating Axon Regeneration in Adult Rats: Studies with Etanercept. Journal of Neuropathology and Experimental Neurology. 68:691-700.

2. Schapansky, J., M. Morissette, Odero, G., Albensi, B., and Glazner GW*. (2009) Neuroregulin b1 enhances peak glutamate-induced intracellular calcium levels through endoplasmmic reticulum calcium release in cultured hippocampal neurons. Submitted to Canadian Journal of Physiology and Pharmacology. (In Press)

3. Salins P, He Y, Olson K, Glazner G, Kashour T, Amara F. (2008) TGF-beta1 is increased in a transgenic mouse model of familial Alzheimer's disease and causes neuronal apoptosis. Neurosci Lett. 430:81-6

4. Francis GJ, Martinez JA, Liu WQ, Xu K, Ayer A, Fine J, Tuor UI, Glazner G, Hanson LR, Frey WH 2nd, Toth C. (2008) Intranasal insulin prevents cognitive decline, cerebral atrophy and white matter changes in murine type I diabetic encephalopathy. Brain. 131:3311-34.

5. V Brussee, Gf Guo, Yy Dong, C Cheng, Ja Martinez, D Smith, Gw Glazner, P Fernyhough, Dw Zochodne (2008) Distal degenerative sensory neuropathy in a long-term type 2 diabetes rat model. Diabetes 57:1664-73

6. Schapansky, J., Olson, K., Van Der Ploeg, R., and Glazner, G* (2007) NF-kB activated by ER calcium release inhibits Ab-mediated expression of CHOP protein; Enhancement by AD-linked mutant presenilin 1 Exp. Neurol.

7. Fernyhough P, Smith DR, Schapansky J, Van Der Ploeg R, Gardiner NJ, Tweed CW, Kontos A, Freeman L, Purves-Tyson TD, Glazner GW*. (2005) Activation of nuclear factor-kappaB via endogenous tumor necrosis factor alpha regulates survival of axotomized adult sensory neurons. J Neurosci. 16;25(7):1682-90.

8. Glazner, GW*. and Fernyhough, P (2002) Neuronal survival in the balance: Are ER membrane proteins the fulcrum? Cell Calcium 32:421-33.

9. Solovyova N, Fernyhough P, Glazner G, and Verkhratsky A. (2002) Xestospongin C empties the ER calcium store but does not inhibit InsP3-induced Ca2+ release in cultured dorsal root ganglia neurones. Cell Calcium.32:49-52.

10. Glazner, GW, Camandola, S, Geiger, JD and Mattson, MP (2001) Endoplasmic reticulum D-myo-inositol 1, 4, B binding activity ink5-trisphosphate-sensitive stores regulate nuclear factor- a calcium-independent manner. J. Biol. Chem. 276:22461-22467.

B. Submitted Refereed Papers

Kathryn Collister, Gary L. Odero, Jason Schapansky, Jonathan Thiessan, Gordon W Glazner and Benedict C. Albensi (2009) "Genetic Background Influences Neuropathology and Hippocampal-dependent Memory in the TgCRND8 Transgenic Mouse Model of Alzheimer’s Disease" Submitted to Journal of Comparative Neurology.

C. Manuscripts to be submitted in 2009:

Mao, J-Y, Binns, K., Pawson, T., Schapansky, J., Olson, K., and Glazner, G. "Release of calcium from endoplasmic reticulum activates a novel protease activity" Olson, K., Schapansky, J., Salins, P., He Y., Amara, M., and Glazner, G. "Cultured cortical neurons from embryonic TgCRND8 mice display Ab-mediated pathology". Smith, D., Gardner, P., and Glazner, G. NF-kB binding levels in DRG following nerve crush are stimulated by loss of electrical signal.

D. Abstracts and Conference Presentations

Nancy Young, Elena Zherebetskaya, Paul Fernyhough, and Gordon Glazner "NF-kB activity in cultured normal and streptozotocin-diabetic dorsal root ganglia neurons regulates axonal growth and morphology" Society for Neuroscience Conference, San Diego, CA, 2007

Smith, D., Tweed, CW., Fernyhough, PF., and Glazner, GW., Role of TNFa-induced activation of NF-kappaB in morphological and functional axon regeneration in axotomized adult sensory neurons. Peripheral Nerve Society, Snowbird, Utah 2007

Olson KL, Schapansky J, Salins P, Yang He, Amara F, Glazner GW, "Cultured Neurons from Embryonic TgCRND8 Mice Display Cell Death, Increased Amyloid Beta Production, and Aberrant Calcium Regulation", International Conference on Alzheimer's and Parkinson's Disease, Salzburg, Austria, 2007 Kathryn Collister, Gary Odero, Kensaki oikawa, Gordon Glazner, and Benedict Albensi "Spatial memory formation and hippocampal function are influenced by background strain but not gender in the TgCRND8 mouse model of Alzheimer’s Disease. Society for Neuroscience Conference, San Diego, CA, 2007

Kelly L. Olson, Jason S. Schapansky, Pradeep Salins, Yang He, Francis M. Amara, and Gordon W. Glazner "Cultured cortical neurons from embryonic TgCRND8 Mice display aberrant calcium regulation and increased cell death". Society for Neuroscience Conference, Atlanta GA, 2006.

Paul Fernyhough, Darrell Smith, Jason Schapansky, and

Gordon Glazner "NF-kB and CREB DNA binding activities are aberrant in sensory ganglia and peripheral nerve of streptozotocin type diabetic rats" Society for Neuroscience Conference, Atlanta GA, 2006.

Christopher Tweed, Darrell Smith, Jason Schapansky, Paul Fernyhough, and Gordon Glazner "Inhibition of TNFa increases early axonal regeneration and reduces NF-kB DNA binding activity in sciatic nerves following nerve injury". Society for Neuroscience Conference, Atlanta GA, 2006.

Kensuke Oikawa, Gary Odero, Darrell Smith, Gordon Glazner, and Benedict Albensi "Impairment of Synaptic Plasticity in Streptozotocin-Diabetic Rats" Society for Neuroscience Conference, Atlanta GA, 2006. Jason Schapansky and Gordon Glazner "Neuregulin-1 enhances glutamate-mediated calcium influx in rat hippocampal neuronal cultures" Society for Neuroscience Conference, Atlanta GA, 2006.

Darrell Smith, Randall Van Der Ploeg, Jason Schapansky, Phillip Gardiner, and Gordon.Glazner "Loss of electrochemical activity Regulates Axotomy-Induced NF-kB Activation In Adult Rat Sensory Neurons". Society for Neuroscience Conference, Atlanta GA, 2006.

Zuocheng Wang, Darrell Smith, Gordon Glazner, Nigel Calcutt, Andrew Mizisin and Paul Fernyhough "Abnormal mitochondrial respiration is normalized by insulin treatment that does not affect hyperglycemia in sensory neurons in diabetic rats". Society for Neuroscience Conference, Atlanta GA, 2006.