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Mark H. Tuszynski, M.D., Ph.D.
Professor of Neurosciences
Director of the Center for Neural Repair

 

This laboratory studies anatomical, electrophysiological and functional plasticity in the intact and injured adult central nervous system. We focus in particular on the functional role of growth factors in modulating plasticity. Models studied in the lab include: 1) mechanisms of learning and memory in the intact adult brain, 2) plasticity and cell degeneration in models of aging and Alzheimer's disease, and 3) axonal plasticity and regeneration after spinal cord injury. In rodent and primate models of spinal cord injury, we examine the influences of growth factors and extracellular matrix molecules in modulating axonal responses to injury and the ability of these substances to promote axonal regeneration. In models of basal forebrain and cortical degeneration in rodents and primates, the ability of neurotrophic factors delivered by gene therapy to modulate cellular plasticity and survival. These studies are relevant to the understanding of aging and neuronal loss in Alzheimer's disease and Parkinson's Disease. In the intact brain, we examine changes in neuronal structure and function that occur during normal learning, and the role of neurotrophic factors in modulating these changes.

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Selected Publications

Weidner N, Ner A, Salimi N, Tuszynski MH. Spontaneous corticospinal axonal plasticity and functional recovery after adult CNS injury. Proc Nat Acad Sci, 2001; 98:3513-3518.

Conner JM, Culberson A, Packowski C, Chiba A, Tuszynski MH. Lesions of the basal forebrain cholinergic system impair task acquisition and abolish cortical plasticity associated with motor skill learning. Neuron, 2003, 38:819-829

Conner JM, Chiba AA, Tuszynski MH. The basal forebrain cholinergic system is essential for cortical plasticity and functional recovery following brain injury. Neuron, 2005, 46:173-9.

Tuszynski MH et al.  A phase I clinical trial of nerve growth factor gene therapy for Alzheimer’s disease. Nature Med, 2005, 11:551-5.

Tuszynski MH.  Challenges to the report of nogo antibody effects in primates.  Nature Med 2006; 12:1231-1232.

Ramanathan D, Conner JM, Tuszynski, MH. A form of motor cortical plasticity that correlates with recovery of function after brain injury. Proc Nat Acad Sci, 2006;10330:11370-11375.

Blesch A, Tuszynski MH. Spinal cord injury: Plasticity, regeneration and the challenge of translational drug development. Trends in Neurosciences. 2009; 32:41-47. PMID: 18977039

Nagahara A, Merrill DA, Coppola G, Tsukada S, Schroder BE, Shaked GM, Wang L, Blesch A, Kim A, Conner JC, Rockenstein E, Chao MV, Koo E, Geschwind D, Masliah, Chiba AA, Tuszynski MH. Neuroprotective effects of BDNF in rodent and primate models of Alzheimer’s disease. Nature Med, 2009, 15:331-337. PMCID: PMC2838375.

Hollis ER, Jamshidi P, Low K, Blesch A, Tuszynski MH.  Induction of corticospinal regeneration by lentiviral trkB-Induced Erk activation, Proc Nat Acad Sci, 2009, 106:7215-7220. PMCID 2678459.

Kadoya K, Tsukada S, Lu P, Coppola G, Geschwind D, Flibin M, Blesch A, Tuszynski MH. Combined intrinsic and extrinsic neuronal mechanisms facilitate bridging axonal regeneration one year after spinal cord injury. Neuron, 2009; 29:165-172. PMCID 2773653.

Alto L, Havton LA, Conner JM, Hollis ER, Blesch A, Tuszynski MH. Chemotropic guidance facilitates axonal regeneration into brainstem targets and synapse formation after spinal cord injury. Nature Neurosci, 2009, 12: 1106-1113. PMCID 2753201.

Tuszynski MH. Community corner: Mutant mice challenged as models of injury in the central nervous system. Nature Med, 2010, 16:860.

Rosenzweig ES, Courtine G, Jindrich DL, Brock JH, Ferguson AR, Strand SC, Nout YS, Roy RR, Miller DM, Beattie MS, Havton LA, Bresnahan JC, Edgerton VR, Tuszynski M. Extensive spontaneous plasticity of corticospinal projections after primate spinal cord injury. Nature Neurosci, 2010, 13:1505-1510.

Nagahara A, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nature Rev Drug Discov, 2011, 10:209-219.

Wang L, Conner JM, Rickert JL, Tuszynski MH. Structural plasticity within highly specific neuronal populations identifies a parcellation of motor learning. Proc Nat Acad Sci, 2011, 108:2545-2550.

Lu P, Blesch A, Graham L, Wang W, Samara R, Banos K, Haringer V, Havton L, Weishaupt M, Bettett D, Fouad K, Tuszynski MH. Motor axonal regeneration after partial and complete spinal cord transection. J Neurosci, 2012, 32: 8208-8218.

Tuszynski MH and Steward O. Concepts and Methods for the Study of Axonal Regeneration in the CNS. Neuron, 2012; 74:1-15.

Lu P, Wang Y, Graham L, McHale K, Gao M, Wu D, Brock J, Blesch A, Rosenzweig ES, Havton LA, Zheng B, Conner JM, Marsala M, Tuszynski MH. Long-distance growth and connectivity of neural stem cells after severe spinal cord injury: Cell-intrinsic mechanisms overcome spinal inhibition. Cell, 2012, in press.