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Morrissey College of Arts and Sciences

Joseph Burdo

adjunct assistant professor

Joseph Burdo

Ph.D., Penn State College of Medicine

Phone: 617-552-3556

Fields of Interest

Hereditary hemochromatosis as a modifier of heavy metal toxicity in the brain, development of a cell culture model of human stroke and identification of neuroprotective compounds using that culture model.

Academic Profile

My doctoral dissertation in the laboratory of James Connor at Penn State College of Medicine focused on iron metabolism in the brain, and how it is related to neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Diseases and Restless Legs Syndrome. We studied how altered iron and iron management protein distribution in the brain was correlated with particular disease states. During this time, we identified a novel mode of transferrin transport in a cell culture model of the blood brain barrier (BBB) that is thought to have a protective capacity for the brain.

For my postdoctoral fellowship I worked with David Schubert of The Salk Institute in La Jolla, California studying several aspects of neurological diseases. One of my projects dealt with identifying the mechanisms of neuroprotection by flavonoids, which are nutritional antioxidant compounds. We were able to determine one of the critical intracellular pathways by which fisetin, a flavonoid found in highest concentrations in fruits such as strawberries and apples, protected against oxidative stress in neurons. This finding is significant because increases in oxidative stress are common in many seemingly diverse neurodegenerative diseases, and also because it indicates a potential way to protective ourselves from these diseases. Another line of research I was involved in dealt with the interaction of Type II diabetes and AD. People with Type II diabetes are significantly more likely to develop AD than non-diabetics, but the mechanism behind this association isn't clear. Using an AD mouse model, we were able to determine that high levels of blood glucose led to earlier development of the AD pathology compared to those AD mice that had normal blood glucose, and we were also able to localize the particular damage in the AD diabetic mice to the endothelial cells of the BBB. After leaving the Salk Institute, I continued on with a similar line of research during two years as a faculty member at Bridgewater State College.

My current research at Boston College has two main facets, one of which is the further identification of novel neuroprotective compounds in a cell culture model of human stroke. In addition to evaluating flavonoids, I have recently begun collaborating with Dr. Charles Hoffman to test the neuroprotective capacity of his phosphodiesterase inhibitors in my stroke model, with early promising results. My second line of research involves clarifying how the iron overload disease hereditary hemochromatosis (HH) modifies the toxicity risk for other heavy metals such as lead and mercury in the brain. A recent study indicated that HH individuals who have elevated levels of bone and blood lead also have increased levels of cognitive decline compared to non-HH individuals with similar levels of elevated bone and blood lead. The mechanism behind this association is unknown. In my lab we have a neuronal cell line that expresses the mutated proteins that cause HH, and we are using that cell line to study how lead and other heavy metals may differentially affect those who suffer from HH.

Representative Publications

Burdo, J., Chen, Q., Calcutt, N., and Schubert, D. 2009. The pathological interaction between diabetes and presymptomatic Alzheimer's disease. Neurobiology of Aging 30(12): 1910–7.

Burdo, J., Schubert, D., and Maher, P. 2008. Glutathione production is regulated via distinct pathways in stressed and non-stressed cortical neurons. Brain Research 1189: 12–22.

Burdo, J., Dargusch, R., and Schubert, D. 2006. Distribution of the cystine/glutamate antiporter system xc- in the brain, kidney, and duodenum. Journal of Histochemistry and Cytochemistry 54(5): 549–57.

Burdo, J.R., Simpson, I.A., Menzies, S., Beard, J., and Connor, J.R. 2003. Regulation of the profile of iron-management proteins in brain microvasculature. Journal of Cerebral Blood Flow and Metabolism 24(1): 67–74.

Burdo, J.R., Antonetti, D.A., Wolpert, E.B., Connor, J.R. 2003. Mechanisms and regulation of transferrin and iron transport in a model blood-brain barrier system. Neuroscience 121(4): 883–90.

Burdo, J.R. and Connor, J.R. 2003. Brain iron uptake and homeostatic mechanisms: An overview. BioMetals 16(1): 63–75.

Burdo, J.R. and Connor, J.R. 2002. Iron transport in the central nervous system. In Molecular and Cellular Iron Transport, CRC Press, pp. 487–508.

Connor, J.R., Menzies, S.L., Burdo, J.R., and Boyer, P.J. 2002. Iron and iron management proteins in neurobiology. Pediatric Neurology 25(2): 118–129.

Zywicke, H.A., van Gelderen, P., Connor, J.R., Burdo, J.R., Garrick, M.D., Dolan, K.G., Frank, J.A., and Bulte, J.W. 2002. Microscopic R2* mapping of reduced brain iron in the Belgrade rat. Annals of Neurology 52(1): 102–105.

Burdo, J.R., Menzies, S.L., Simpson, I.A., Garrick, L.M., Garrick, M.D., Dolan, K.G., Haile, D.J., Beard, J.L., and Connor, J.R. 2001. Distribution of divalent metal transporter 1 and metal transport protein 1 in the normal and Belgrade rat. Journal of Neuroscience Research 66: 1198–1207.

Georgieff, M.K., Wobken, J.K., Welle, J., Burdo, J.R, Connor, J.R. 2000. Identification and localization of divalent metal transporter-1 (DMT-1) in term human placenta. Placenta 21(8): 799–804.

Burdo, J.R., Martin, J., Menzies, S.L., Dolan, K.G., Romano, M.A., Fletcher, R.J., Garrick, M.D., Garrick, L.M., and Connor, J.R. 1999. Cellular distribution of iron in the brain of the Belgrade rat. Neuroscience 93(3): 1189–1196.