SCoBIRC FACULTY

Pamela E. Knapp, Ph.D.

Associate Professor,
Anatomy and Neurobiology

The Ohio State University (1983). Postdoctoral training at Wayne State University.

Research Interests

Glial Cell Function and Myelination in Normal Development and Injury
Normal function of the CNS depends upon the generation of adequate numbers of oligodendrocytes which form myelin and ensheath axons. When glial cell development is compromised and/or myelination is inhibited, both sensory and motor pathways are affected. In some CNS diseases, such as multiple sclerosis, the loss of mature, myelinating oligodendrocytes is a key element in the clinical pathology of the disease. Loss of myelinating oligodendrocytes also contributes to functional deficits following traumatic brain and spinal cord injuries.

The underlying goal of the majority of projects in the laboratory is to understand the signaling events which lead to the programmed death of oligodendrocytes in development and in disease or injury situations where myelin is lost. Disrupting these apoptotic pathways should promote the survival of oligodendrocytes and the preservation and maintenance of myelin in demyelinating conditions. Current projects in the laboratory explore: 1) whether increased activity in the PI 3-kinase / Akt pathway can protect oligodendrocytes from soluble toxic factors such as TNFa, ceramide and glutamate; 2) how endogenous and exogenous opioids modulate oligodendocyte development and function; 3) whether perforin and other proteins released from the cytolytic granules of activated T-cells are directly toxic to oligodendrocytes.

The laboratory uses tissue culture as a primary approach to sorting out the complex signaling interactions which occur between different types of glial cells and/or neurons during development and after injury. In situ injury and disease models are also employed when appropriate. Experimental techniques used in the lab include cell transfection, immunohistochemistry, in situ hybridization, ratiometric Ca++ imaging, quantitative immunoblotting, PCR and unbiased stereology.

Representative Publications

Knapp, P.E. (1997). Injury stimulates outgrowth and motility of oligodendrocytes grown in vitro. Exp. Cell Res., 234: 7-17.

Knapp, P.E., Maderspach, K. and Hauser, K.F. (1998). Endogenous opioid system in developing normal and jimpy oligodendrocytes: ? and ? opioid receptors mediate differential mitogenic and growth responses. Glia, 22: 189-201.

Springer, J.E., Azbill, R.D. and Knapp, P.E. (1999). Activation of the caspase-3 apoptotic cascade in spinal cord trauma. 5(8): 943-946, Nature Medicine.

Knapp, P.E., Itkis, O.S. and Mata, M. (2000). Neuronal interaction determines the expression of the ?-2 isoform of Na-K ATPase in oligodendrocytes. Dev. Brain Res., 125: 89-97.

Hauser, K.F., Knapp, P.E. and Turbek, C.S. (2001). Structure-activity analyis of dynorphin A toxicity in spinal cord neurons: Intrinsic neurotoxicity of dynorphin A and its carboxyl-terminal, non-opioid metabolites. Exp. Neurol., 168:78-87.

Knapp, P.E., Itkis, O.S., Zhang, L., Spruce, B.A., Bakalkin, G. and Hauser, K.F. (2001). Opiate signaling in oligodendrocytes: possible autocrine effects on cell survival and development. Glia, 35(2):156-165.

Nottingham, S.A., Knapp, P.E., Springer, J.E. (2002). FK506 treatment inhibits caspase-3 activation and promotes oligodendroglial survival following traumatic spinal cord injury. Exp. Neurol., 177:242-251.

Knapp, P.E. and Adams, M.A. (2003). Epidermal growth factor promotes oligodendrocyte differentiation and enhances survival and regrowth after injury. Exp. Cell Res.,In Press.