SCoBIRC FACULTY

Patrick G. Sullivan, Ph.D.

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)

Dr. Sullivan and his lab

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
(selected from 72 peer-reviewed publications)

Scheff, S.W., Sullivan, P.G., (1999). Cyclosporin A Significantly Ameliorates Cortical Damage Following Experimental Traumatic Brain Injury in Rodents. Journal of Neurotrauma, 16(9), 783-792.

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.

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.,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.

Brown, M.R., Sullivan, P.G., (co-first author), Dorenbos, K.A., Modafferi, E.F., Geddes, J.W., Steward, O., (2004). Nitrogen Disruption of Synaptoneurosomes: An Alternative Method to Isolate Total or Synaptic Brain Mitochondria. Journal of Neuroscience Methods, 137, 299-303.

Sullivan, P.G., Rabchevsky, A.G., Waldmeier, P.C., Springer, J.E., (2005).  Mitochondrial Permeability Transition in CNS Trauma: Cause or Effect of Neuronal Cell Death? Invited Review, Journal of Neuroscience Research, 79, 231-239.

Sullivan, P.G. (2005). Interventions with Neuroprotective Agents: Novel Targets and Opportunities. Epilepsy and Behavior, Suppl 3:12-17.

Singh, I.N., Sullivan, P.G., (co-first author), Deng, Y. Mbye, L.H., Hall, E.D. (2006). Time Course of Post-Traumatic Mitochondrial Oxidative Damage and Dysfunction in a Mouse Model of Focal Traumatic Brain Injury: Implications for Neuroprotective Therapy. Journal of Cerebral Blood Flow & Metabolism, 26, 1407-1418.

Sullivan, P.G., Balke, C.W., Esser, K.A., (2006). Mitochondrial Buffering of Calcium in the Heart. Potential Mechanism for Linking cyclic Energetic Cost with Energy Supply? Circulation Research, 99, 109-110.

Nukala, V.N., Singh, I.N., Davis, L.M., Sullivan, P.G. (2006). Cryopreservation of Brain Mitochondria: A Novel Methodology for Functional Studies. Journal of Neuroscience Methods, 152, 48-54.

Opii, W.O., Nukala, V.N., Sultana, R., Day, K.M., Merchant, M.L., Klein, J.B., Sullivan, P.G., Butterfield, D.A., (2007). Proteomic Identification of Oxidized Mitochondrial Proteins Following Experimental Traumatic Brain Injury. Journal of Neurotrauma, 24(5), 772-789.

Naga, K.K, Sullivan, P.G., Geddes, J.W., (2007). High Cyclophilin D content of Synaptic Mitochondria Results in Increased Vulnerability to Permeability Transition. Journal of Neuroscience, 27(28), 7469-7475.

Sullivan, P.G., Krishnamurthy, S., Patel, S.P., Pandya, J.D., Rabchevsky, A.G., (2007). Temporal Characterization of Mitochondrial Bioenergetics after Spinal Cord Injury. Journal of Neurotrauma, 24(6), 991-999.

Pandya, J.D., Pauly, J.R., Nukala, V.N., Sebastian, Day, K.M., A.H., Korde, A.M., Springer, J.E., Maragos, W.F., Hall, E.D., Sullivan, P.G. (2007). Mitochondrial Uncouplers as Possible Therapeutic Interventions following Traumatic Brain Injury. Journal of Neurotrauma, 24, 798-811.

Hall, E.D., Deng, Y., Cho, W., Sullivan, P.G., (2008). Evolution of Post-Traumatic Neurodegeneration after Controlled Cortical Impact Traumatic Brain Injury in Mice and Rats. Journal of Neurotrauma, 25(3), 235-247.

Pandya, J.D., Pauly, J.R., Sullivan, P.G., (2009). The Optimal Dosage and Window of Opportunity to Maintain Mitochondrial Homeostasis following Traumatic Brain Injury using the Uncoupler FCCP. Experimental Neurology, 218(2), 381-389.

Davis, L.M., Pauly, J.R, Readnower, R, Rho, J.M., Sullivan, P.G., (2008). Fasting is Neuroprotective Following Traumatic Brain Injury. Journal of Neuroscience Research, 86, 1812-1822.

Gash, D.M., Rutland, K., Carter, N., Sullivan, P.G., Bing, G., Cass, W., Pandya, J.D., Liu, M., Choi, D.Y., Hunter, R.L., Gerhardt, G.A., Smith, C.D., Slevin, J.T., Prince, T.S., (2008).  Trichloroethylene: Parkinsonism and Complex 1 Mitochondrial Neurotoxicity. Annals of Neurology, 63(2), 184-192.

Patel S.P., Sullivan P.G., Lyttle T.S., Rabchevsky A.G., (2010). Acetly-L-carnitine Ameliorates Mitochondrial Dysfunction Following Contusion Spinal Cord Injury. Journal of Neurochemistry, 114(1), 291-301.

Readnower R.D., Chavko M., Adeeb S., Conroy M.D., Pauly J.R., McCarron, R.M., Sullivan P.G., (2010). Increase in Blood-Brain barrier Permeability, Oxidative Stress, and activated Microglia in a Rat Model of Blast-induced Traumatic Brain Injury. Journal of Neuroscience Research, 88(16), 3530-3539.

Akundi R. S., Huang  Z., Eason J., Pandya J. D., Cass, W.A., Sullivan P. G., Büeler H., (2011). Increased Jun N-terminal kinase activity and abnormal innate immune system gene regulation in the nigrostriatal pathway of PINK1-deficient mice. PLOSONE, 6(1):e16038.

Sullivan, P.G., Sebastian, A.H., Hall, E.D., (2011). Therapeutic Window Analysis of the Neuroprotective Effects of Cyclosporine A after Traumatic Brain Injury. Journal of Neurotrauma, (In Press).

Sauerbeck A.D., Gao J., Readnower R.D., Liu M., Pauly J.R., Bing G., Sullivan P.G., (2011). Pioglitazone attenuates mitochondrial dysfunction, cognitive impairment, cortical tissue loss, and inflammation following traumatic brain injury. Experimental Neurology, (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.

Lifshitz, 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.

Rho, J.M. and Sullivan, P.G., (2006). How does the Ketogenic Diet Work? A Look into Mechanisms of Action. Epilepsy Research, 68, 153-160.

Mattiasson, G. and Sullivan, P.G., (2006). The Emerging Roles of UCP2 in Health and Disease. Invited Review.  Antioxidants and Redox Signaling, 8, 1-38.

Davis, L.M. and Sullivan P.G., (2010). Mitochondrial Damage in Traumatic CNS Injury. In: Acute Neuronal Injury: The Role of Excitotoxic Programmed Cell Death, D. G,Fujikawa (eds.), Springer Press, 157-168.

Readnower R.D. and Sullivan P.G., (2010). Neuroprotective Strategies Using Antiepileptic Drugs. In: Epilepsy: Mechanisms, Models, and Translational Perspectives, CRC Press, 11, 173-180.