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Visiting speaker: Dr. James Connor, Center for Aging and Neurodegenerative Diseases
2:00pm-3:00pm, Mar 6, 2019
Room 3402ABC, third floor, Djavad Mowafaghian Centre for Brain Health
- Iron metabolism in the brain and neural system, brain cancer stem cells, blood-brain barrier
- Systems/Organs: Neural, brain
- Cell/Cellular compartments: Neurons, intracellular trafficking of ferritin
- Signaling pathways: Iron sensing and signaling; immunological responses to cancer
- Diseases/Conditions: Glioblastoma; Alzheimer’s, Parkinson’s Diseases (AD, PD); Multiple Sclerosis (MS);
- Focus Groups: Neuroscience; Cancer Stem Cells.
Research description: Translational
We have focused on a number of mouse and rat mutants as a model of human diseases in which the ability to acquire, mobilize or store iron has been disrupted. In the context of these studies, we have generated a very promising mouse line in which the gene for the iron storage protein, ferritin, has been deleted. This model is helping to understand the contribution of loss of brain iron homeostatic mechanisms to those changes seen in the brain with AD, PD and MS. In the course of these studies on ferritin, we found that in addition to the cytoplasmic location, ferritin can be found in cell nuclei under some conditions. This observation has led us to basic molecular studies on DNA binding and protection as well as intracellular trafficking of ferritin. The evidence strongly indicates that nuclear ferritin is associated with tumorigenesis. In addition, we have identified mutations in the Hfe gene as a risk factor for Alzheimer’s Disease and Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease).
Isolation and purification cancer stem cells from brain tumors; to examine the consequences of iron mismanagement in the brain, we utilize both cell culture and animal models. The cell culture model seeks to identify the intracellular events associated with iron-induced stress and uses state of the art microscopic and fluorimetric techniques. Sara Robb received the Marian Kies Award from the American Society of Neurochemistry for outstanding graduate research for developing this model in my laboratory.