Distinguished Professor of Neurosurgery, Neural, and Behavioral Sciences and Pediatrics
Vice Chair of Neurosurgery Research
Director, Center for Aging and Neurodegenerative Diseases
Department: Neurosurgery
Email: jconnor@pennstatehealth.psu.edu
Phone: 717-531-4541
Research Interests:
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).
Technical expertise: 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.
Selected Publications:
- Meadowcroft MD, Wang J, Purnell CJ, Peters DG, Eslinger PJ, Neely EB, Gill DJ, Vasavada M, Ali-Rahmani F, Yang QX, Connor JR. Reduced white matter MRI transverse relaxation rate in cognitively normal H63D-HFE human carriers and H67D-HFE mice. Brain Imaging Behav. 2016 Dec; 10(4):1231-1242. PMID: 26660104.
- Duck KA, Connor JR. Iron uptake and transport across physiological barriers. Biometals. 2016 Aug; 29(4):573-91.
- Lee SY, Slagle-Webb B, Sheehan JM, Zhu J, Muscat JE, Glantz M, Connor JR. HFE polymorphisms affect survival of brain tumor patients. J Neurooncol. 2015 Mar; 122(1):97-104.
Related Links: