SCoBIRC FACULTY

Patrick G. Sullivan, Ph.D.

Associate Director, SCoBIRC
Associate Professor, Spinal Cord & Brain Injury Research Center and Anatomy & Neurobiology

Ph.D. in Anatomy and Neurobiology, University of Kentucky (2000). Postdoctoral at the Reeve-Irvine Research Center, University of California at Irvine.
Curriculum Vitae (pdf)

Research Interests

The Role of Mitochondrial Dysfunction in the Neuropathology of Traumatic Brain and Spinal Cord Injury
Traumatic brain (TBI) and spinal cord injuries (SCI) render devastating health problems in the United States with an annual cost of approximately 25 billion dollars. This has initiated an enormous focus on the development and discovery of neuroprotective and/or pro-regenerative agents for the treatment of TBI and SCI. Nevertheless, the underlying mechanism(s) of neuronal degeneration and progressive tissue destruction that occurs following such injuries are not fully understood. To begin exploring the cellular and/or molecular mechanisms underlying the pathophysiology of TBI and SCI, it is important to focus on key regulatory steps in the cell death process. Recent evidence indicates that mitochondria, long-known as the “powerhouse” of the cell, play a pivotal role in the cell death cascade. In support of this hypothesis, we have recently demonstrated that intrinsic differences in mitochondria can confer resistance to excitotoxic cell death. We also have that evidence that by manipulating mitochondrial uncoupling we can modulate neuronal responses to excitotoxic insult and injury.

To further elucidate the role mitochondria in secondary neuronal cell death, the specific research goals of the laboratory are to: 1) determine the underlying genetic and molecular mechanisms of resistance to excitotoxic cell death; 2) establish whether the upregulation of mitochondrial uncoupling proteins are neuroprotective following SCI and TBI; 3) define the mechanisms that mediate intrinsic differences in brain and spinal cord mitochondria in order to design effective strategies for neuroprotective and regenerative therapeutics.

Representative Publications

Sullivan, P.G., Keller, J.N., Mattson, M.P., Scheff, S.W., (1998). Traumatic Brain Injury Alters Synaptic Homeostasis: Implications for Impaired Mitochondrial and Transport Function. Journal of Neurotrauma, 15(10), 789-798.

Sullivan, P.G., Bruce-Keller, A.J., Rabchevsky, A.G., Christakos, S., St. Clair, D.K., Mattson, M.P., Scheff, S.W., (1999). Exacerbation of Damage and Altered NF B Activation in Mice Lacking Tumor Necrosis Factor Receptors after Traumatic Brain Injury. Journal of Neuroscience, 19(15), 6248-6256.

Sullivan, P.G., Thompson, M.B., Scheff, S.W., (1999). Cyclosporin A Attenuates Acute Mitochondrial Dysfunction following Traumatic Brain Injury. Experimental Neurology, 160, 226-234.

Sullivan, P.G., Geiger, J.D., Mattson, M.P., Scheff, S.W., (2000). Dietary Supplement Creatine Protects against Traumatic Brain Injury. Annals of Neurology, 48(5), 723-729.

Jiang, D., Sullivan, P.G., (co-first author), Sensi, S.L., Steward, O., Weiss, J.H., (2001). Zn2+ Induces PTP opening and Release of Pro-apoptotic Peptides from Neuronal Mitochondria. Journal of Biological Chemistry, December 276(50), 47524-47529.

Sullivan, P.G., Keller, J.N., Bussen, W.L., Scheff, S.W., (2002). Cytochrome C Release and Caspase Activation after Traumatic Brain Injury. Brain Research, 949, 88-96.

Sullivan, P.G., Dube, C., Dorenbos, K.D., Steward, O., Baram, T.Z., (2003). Mitochondrial uncoupling protein-2 protects the immature brain from excitotoxic neuronal death. Annals of Neurology, 53, 711-717.

Sullivan, P.G., Rippy, N.A., Rho, J.M., (2004). The Ketogenic Diet Enhances Increases Mitochondrial Uncoupling Protein Levels And Activity In Mouse Hippocampus. Annals of Neurology, 55, 576-580

Sullivan, P.G., Rabchevsky, A.G., Keller, J.N., Lovell, M.A., Scheff, S.W., (2004). Intrinsic Differences in Isolated Brain and Spinal Cord Mitochondria: Implication for Therapeutic Interventions following Injury. Journal of Comparative Neurology, 474, 524-534.

Sullivan, P.G., Dragicevic, N.B., Deng, J.H, Bai, Y., Dimayuga, E., Keller, J.N., (2004). Proteasome Inhibition alters Neural Mitochondrial Homeostasis and Increases Dependence on Glycolysis. Journal of Biological Chemistry, 279, 20699-21707.

Brown, M.B., Geddes, J.W., Sullivan, P.G., (2004). Brain region-specific, age-related, alterations in mitochondrial responses to elevated calcium. Journal of Bioenergetics and Biomembranes, 36, 401-406.

Sensi, S.L.,Ton-That, D., Sullivan P.G., Jonas, E.A., Gee, K.R., Kaczmarek, L.K., Weiss J.H., (2003). Modulation of mitochondrial function by endogenous Zn2+ pools. Proceeding National Academy of Science, 100, 6157-6162.

Sullivan, P.G., Rabchevsky, A.G., Waldmeier, P.C., Springer, J.E., (2004). Mitochondrial Permeability Transition in CNS Trauma: Cause or Effect of Neuronal Cell Death? Journal of Neuroscience Research, 79, 213-239.

Nukala, V.N., Singh, I.N., Davis, L.D., Sullivan, P.G. (2005). Cryopreservation of Brain Mitochondria: A Novel Methodology for Functional Studies. Journal of Neuroscience Methods, (In Press).

Sullivan, P.G. (2005). Interventions with Neuroprotective Agents: Novel Targets and Opportunities. Epilepsy and Behavior, (In Press).

Rho, J.M. and Sullivan, P.G. (2005). How does the Ketogenic Diet Work? A Look into Mechanisms of Action. Epilepsy Research, (In Press).

Sullivan, P.G., Davis, L.M., Rho, J.M (2005). Oxidative Stress, the Ketogenic Diet and Epilepsy. Cell Science Reviews, (In Press).

Invited Reviews and Book Chapters

Hall, E.D., Sullivan, P.G., (2004). Preserving Function in Acute Nervous System Injury. In: Neuroscience, Molecular Medicine and the Therapeutic Transformation of Neurology, S.G Waxman (eds.), Elsevier/Academic Press.

Sullivan, P.G., Springer, J.E., Hall, E.D., Scheff, S.W., (2004). Mitochondrial Uncoupling as a Therapeutic Target Following Neuronal Injury. Invited Review, Journal of Bioenergetics and Biomembranes, 36, 353-356.

Lipshitz, J., Sullivan, P.G., Hovda, D.A., McIntosh, T.K., (2005). Mitochondrial Damage and Dysfunction in Traumatic Brain Injury. Invited Review, Mitochondrion, 4, 705-713.

Sullivan, P.G., Brown, M.R., (2005). Mitochondrial Aging and Dysfunction in Alzheimer's Disease. Invited Review, Progress in Neuro-Psychopharmacology & Biological Psychiatry, 27, 407-410.

Mattiasson, G. and Sullivan, P.G., (2005). The Emerging Roles of UCP2 in Health and Disease. Invited Review, Antioxidants and Redox Signaling, (In Press).