Linda M Parysek

One project focuses on understanding the molecular events required for effective nerve regeneration. We are determining how genes respond to peripheral nerve injury by identifying “injury-response elements” in transgenes that are activated after nerve crush in mice. One gene that is activated after nerve injury encodes peripherin, a subunit of the neuronal intermediate filament cytoskeleton. We are analyzing the role of peripherin in nerve regeneration by carrying out nerve re-growth studies in mice in which the peripherin filaments in sensory neurons are disrupted by expression of a dominant-negative mutant peripherin transgene. In a second project, we are studying the efficacy of defective herpes viruses in killing brain tumors.

The long-term objective of the work of this laboratory is to understand the role of intermediate filaments (IF) in neural development. IF are thought to be structurally important in the development and maintenance of cell morphology. Studies have shown that the expression of proteins that compose IF changes as cells differentiate. This data indicates that IF may be involved in functions specific to the differentiated state of cell or to the process of differentiation. The goals pertinent to our current work are to study the importance of one particular IF protein, peripherin, to differentiation and function in vivo and in vitro. To determine the role of the peripherin, the effects of a disrupted IF network and peripherin gene knockout is being examined in transgenic mice. Analyses of the role of peripherin IF in normal neuronal function should lead to an improved understanding of the processes leading to abnormal accumulations of IF. These accumulations are prominent pathologic findings in many important degenerative neurologic diseases.

Grant: #R01-NS-035313 Investigators:Parysek, Linda 02-15-2005 -01-31-2010 National Institute of Neurological Disorders and Stroke Role of the Cytoskeleton in Regeneration and Sprouting Role:PI $1,188,504.00 Closed Level:Federal

Grant: #1-S10-RR-14689-01-A1-S0-E0 Investigators:Parysek, Linda 04-01-2001 -03-31-2002 National Center for Research Resources Transmission Electron Microscope Role:PI $367,440.00 Closed Level:Federal

Grant: #5-R01-NS-35313-04-A0-S0-E0 Investigators:Parysek, Linda 06-01-1997 -05-31-2002 National Institute of Neurological Disorders and Stroke The Role of the Cytoskeleton in Neuronal Regeneration Role:PI $810,886.00 Closed Level:Federal

Grant: #URC Interdisciplinary 2012-13 Investigators:Parysek, Linda 05-01-2013 -05-31-2014 UC's University Research Council The Essential Role of Mitofilin in Mitochondrial Function Role:PI $25,000.00 Active Level:Internal UC

Peer Reviewed Publications

Hennigan, R F; Moon, C A; Parysek, L M; Monk, K R; Morfini, G; Berth, S; Brady, S; Ratner, N (2013. ) The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38(SAPK) pathway.Oncogene, , 32 (9 ) ,1135-43 More Information

Olshavsky, Nicholas A; Comstock, Clay E S; Schiewer, Matthew J; Augello, Michael A; Hyslop, Terry; Sette, Claudio; Zhang, Jinsong; Parysek, Linda M; Knudsen, Karen E (2010. ) Identification of ASF/SF2 as a critical, allele-specific effector of the cyclin D1b oncogene.Cancer research, , 70 (10 ) ,3975-84 More Information

Seeley, Sarah L; Bosco, Emily E; Kramer, Elizabeth; Parysek, Linda M; Knudsen, Erik S (2007. ) Distinct roles for RB loss on cell cycle control, cisplatin response, and immortalization in Schwann cells.Cancer letters, , 245 (1-2 ) ,205-17 More Information

Belecky-Adams, Teri; Holmes, Michael; Shan, Yuqing; Tedesco, C Susan; Mascari, Carla; Kaul, Ajay; Wight, David C; Morris, Randal E; Sussman, Mark; Diamond, Jack; Parysek, Linda M (2003. ) An intact intermediate filament network is required for collateral sprouting of small diameter nerve fibers. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 23 (28 ) ,9312-9

Miller, Shyra J; Li, Hongzhen; Rizvi, Tilat A; Huang, Yuan; Johansson, Gunnar; Bowersock, Jason; Sidani, Amer; Vitullo, John; Vogel, Kristine; Parysek, Linda M; DeClue, Jeffrey E; Ratner, Nancy (2003. ) Brain lipid binding protein in axon-Schwann cell interactions and peripheral nerve tumorigenesis. Molecular and cellular biology, , 23 (6 ) ,2213-24

Uveges, Thomas E; Shan, Yuqing; Kramer, Bridget E; Wight, David C; Parysek, Linda M (2002. ) Intron 1 is required for cell type-specific, but not injury-responsive, peripherin gene expression. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 22 (18 ) ,7959-67

Weiner, N E; Pyles, R B; Chalk, C L; Balko, M G; Miller, M A; Dyer, C A; Warnick, R E; Parysek, L M (1999. ) A syngeneic mouse glioma model for study of glioblastoma therapy. Journal of neuropathology and experimental neurology, , 58 (1 ) ,54-60

Janczewski, K H; Chalk, C L; Pyles, R B; Parysek, L M; Unger, L W; Warnick, R E (1998. ) A simple, reproducible technique for establishing leptomeningeal tumors in nude rats. Journal of neuroscience methods, , 85 (1 ) ,45-9

Pyles, R B; Santoro, I M; Groden, J; Parysek, L M (1998. ) Novel protein isoforms of the APC tumor suppressor in neural tissue.Oncogene, , 16 (1 ) ,77-82 More Information

Pyles, R B; Warnick, R E; Chalk, C L; Szanti, B E; Parysek, L M (1997. ) A novel multiply-mutated HSV-1 strain for the treatment of human brain tumors.Human gene therapy, , 8 (5 ) ,533-44 More Information

Cui, C; Stambrook, P J; Parysek, L M (1995. ) Peripherin assembles into homopolymers in SW13 cells. Journal of cell science, , 108 ( Pt 10) ,3279-84

Blumenfeld, A; Lucente, D E; Trofatter, J A; Lerner, T; Slaugenhaupt, S A; Liebert, C B; Monahan, M; Haines, J L; Gusella, J F; Breakefield, X O; Parysek, L M (1995. ) Peripherin gene is linked to keratin 18 gene on human chromosome 12. Somatic cell and molecular genetics, , 21 (1 ) ,83-8

Foley, J; Witte, D; Chiu, F C; Parysek, L M (1994. ) Expression of the neural intermediate filament proteins peripherin and neurofilament-66/alpha-internexin in neuroblastoma. Laboratory investigation; a journal of technical methods and pathology, , 71 (2 ) ,193-9

Foley, J; Ley, C A; Parysek, L M (1994. ) The structure of the human peripherin gene (PRPH) and identification of potential regulatory elements.Genomics, , 22 (2 ) ,456-61 More Information

Bi, W L; Parysek, L M; Warnick, R; Stambrook, P J (1993. ) In vitro evidence that metabolic cooperation is responsible for the bystander effect observed with HSV tk retroviral gene therapy.Human gene therapy, , 4 (6 ) ,725-31 More Information

Belecky-Adams, T; Wight, D C; Kopchick, J J; Parysek, L M (1993. ) Intragenic sequences are required for cell type-specific and injury-induced expression of the rat peripherin gene. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 13 (12 ) ,5056-65

Sleight, B J; Soukup, S; Ballard, E T; Parysek, L M S-cells from a highly N-myc-amplified neuroblastoma are tumorigenic in nude mice. Anticancer research, , 13 (6A ) ,2031-6

Foley, J; Cohn, S L; Salwen, H R; Chagnovich, D; Cowan, J; Mason, K L; Parysek, L M (1991. ) Differential expression of N-myc in phenotypically distinct subclones of a human neuroblastoma cell line. Cancer research, , 51 (23 Pt 1 ) ,6338-45

Parysek, L M; McReynolds, M A; Goldman, R D; Ley, C A (1991. ) Some neural intermediate filaments contain both peripherin and the neurofilament proteins.Journal of neuroscience research, , 30 (1 ) ,80-91 More Information

Vickers, J C; Vitadello, M; Parysek, L M; Costa, M Complementary immunohistochemical distribution of the neurofilament triplet and novel intermediate filament proteins in the autonomic and sensory nervous system of the guinea-pig. Journal of chemical neuroanatomy, , 4 (4 ) ,259-70

Oblinger, M M; Wong, J; Parysek, L M (1989. ) Axotomy-induced changes in the expression of a type III neuronal intermediate filament gene. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 9 (11 ) ,3766-75

Brody, B A; Ley, C A; Parysek, L M (1989. ) Selective distribution of the 57 kDa neural intermediate filament protein in the rat CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 9 (7 ) ,2391-401

Parysek, L M; Chisholm, R L; Ley, C A; Goldman, R D (1988. ) A type III intermediate filament gene is expressed in mature neurons. Neuron, , 1 (5 ) ,395-401

Parysek, L M; Goldman, R D (1988. ) Distribution of a novel 57 kDa intermediate filament (IF) protein in the nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 8 (2 ) ,555-63

Kuczmarski, E R; Routsolias, L; Parysek, L M (1988. ) Proteolytic fragmentation of Dictyostelium myosin and localization of the in vivo heavy chain phosphorylation site.Cell motility and the cytoskeleton, , 10 (4 ) ,471-81 More Information

Kuczmarski, E R; Tafuri, S R; Parysek, L M (1987. ) Effect of heavy chain phosphorylation on the polymerization and structure of Dictyostelium myosin filaments. The Journal of cell biology, , 105 (6 Pt 2 ) ,2989-97

Parysek, L M; Goldman, R D (1987. ) Characterization of intermediate filaments in PC12 cells. The Journal of neuroscience : the official journal of the Society for Neuroscience, , 7 (3 ) ,781-91

Olmsted, J B; Asnes, C F; Parysek, L M; Lyon, H D; Kidder, G M (1986. ) Distribution of MAP-4 in cells and in adult and developing mouse tissues. Annals of the New York Academy of Sciences, , 466 ,292-305

Parysek, L M; del Cerro, M; Olmsted, J B (1985. ) Microtubule-associated protein 4 antibody: a new marker for astroglia and oligodendroglia. Neuroscience, , 15 (3 ) ,869-75

Parysek, L M; Wolosewick, J J; Olmsted, J B (1984. ) MAP 4: a microtubule-associated protein specific for a subset of tissue microtubules. The Journal of cell biology, , 99 (6 ) ,2287-96

Parysek, L M; Asnes, C F; Olmsted, J B (1984. ) MAP 4: occurrence in mouse tissues. The Journal of cell biology, , 99 (4 Pt 1 ) ,1309-15

Olmsted, J B; Cox, J V; Asnes, C F; Parysek, L M; Lyon, H D (1984. ) Cellular regulation of microtubule organization. The Journal of cell biology, , 99 (1 Pt 2 ) ,28s-32s

Parysek, L M; Eckert, B S (1984. ) Vimentin filaments in spreading, randomly locomoting, and f-met-leu-phe-treated neutrophils. Cell and tissue research, , 235 (3 ) ,575-81

Eckert, B S; Daley, R A; Parysek, L M (1982. ) Assembly of keratin onto PtK1 cytoskeletons: evidence for an intermediate filament organizing center. The Journal of cell biology, , 92 (2 ) ,575-8

Eckert, B S; Daley, R A; Parysek, L M (1982. ) In vivo disruption of the cytokeratin cytoskeleton in cultured epithelial cells by microinjection of antikeratin: evidence for the presence of an intermediate-filament-organizing center. Cold Spring Harbor symposia on quantitative biology, , 46 Pt 1 ,403-12

Scientist, Cell Biologist,Protein Purification,Nucleic Acid Hybridization,Fibrils and Filaments,Nervous System,Mammalian (non-human) Developmental Biology