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Thomas Jefferson University - Piera Pasinelli, Ph.D.
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Piera Pasinelli, Ph.D.
Biochemistry and Molecular Biology
Thomas Jefferson University
Department of Biochemistry and Molecular Biology
Farber Institute for Neurosciences
Weinberg Unit for ALS Research
Assistant Professor
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Mailing Address
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900 Walnut Street, JHN-451-F
Philadelphia, Pennsylvania 19107
United States
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Qualifications
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Post-Doctoral, 1996-2000
Harvard Medical School-Massachusetts General Hospital (Neurology)
Ph.D., 1996
Utrecht University-Rudolf Magnus Institute for Neurosciences, The Netherlands (Neurobiochemistry)
B.S., 1992
University of Milan, Italy, (Chemistry and Neuropharmacology)
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Expertise and Research Interests
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Research in the laboratory focuses on the study of the cellular and molecular events that lead to motor neuron death in Amyotrophic Lateral Sclerosis or Lou Gehrig''s disease.
In particular, we study the molecular mechanism(s) by which mutations in the gene encoding for the cytosolic copper-zinc superoxide dismutase (SOD1) cause motor neuron degeneration in a subset of patients with the familial form of the disease. The ultimate goal is to identify potential therapeutic targets.
To this end, work in the laboratory develops in two components
1) Basic research
2) Drug screening or translational research
Basic research:
Mutations in SOD1 cause motor neuron death through gain of one or more toxic properties that are not fully delineated. This toxicity impairs multiple cellular functions. Among these, characteristic features of ALS are mitochondrial abnormalities and activation of cell death genes. Our basic research program studies
a) the molecular switches that, upon mutation, convert SOD1 (normally a pro-survival protein) into a toxic molecule using in vitro biochemical approaches,
b) the pathological mechanisms governing mutant SOD1-mediated cell death and mitochondrial dysfunction in neuronal cultures and transgenic animal models.
Drug screening:
Basic research gets translated into the development of cell-based high throughput assays
to screen for potential ALS therapeutics. The final goal is to test promising drugs in the ALS mice.
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Keywords
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Neurobiology, Amyotrophic Lateral Sclerosis, Neurodegeneration, Neurodegenerative Disease, Motor Neurons, Cell death, Mitochondria
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Publications
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- Pasinelli P, Brown RH. Molecular biology of amyotrophic lateral sclerosis: insights from genetics. (2006) Nat Rev Neurosci., 7(9):710-23.
- Boston-Howes W, Gibbs SL, Williams EO, Pasinelli P, Brown RH Jr, Trotti D. Caspase-3 cleaves and inactivates the glutamate transporter EAAT2. (2006) J. Biol Chem., 281(20):14076-84.
- Broom WJ, Ay I, Pasinelli P, Brown RH, Jr. Inhibition of SOD1 expression by mitomycin C is a non-specific consequence of cellular toxicity. (2006) Neurosci Lett., 393(2-3):184-8.
- P. Pasinelli, MB. Belford, N. Lennon, BJ Bacskai, BT Hyman, D Trotti and RH Brown, Jr. Amyotrophic lateral sclerosis-associated mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria. (2004) Neuron, 43(1): 19-30.
- Zhu S, Li M, Figueroa BE, Liu A, Stavrovskaya IG, Pasinelli P, Beal MF, Brown RH Jr, Kristal BS, Ferrante RJ, Friedlander RM. Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice (2004). J Neurosci., ;24(26):5909-
- Maxwell M., Pasinelli P.., Kazantsev AG, Brown RH Jr. RNA interference-mediated silencing of mutant superoxide dismutase rescues cyclosporin A-induced death in cultured neuroblastoma cells. (2004) Proc. Natl. Acad. Sci., 101(9):3178-83.
- Dangond F, Hwang D, Camelo S, Pasinelli P, Frosch MP, Stephanopoulos G, Stephanopoulos G, Brown RH Jr, Gullans SR. Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. (2004) Physiol. Genomics. 16(2):229-39.
- Cudkowicz ME, Pastusza KA, Sapp PC, Mathews RK, Leahy J, Pasinelli P, Francis JW, Jang D, Andersen JK, Brown RH Jr. Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity. (2002) Neurology, 59(5): 729-734.
- Nagai M, Aoki M, Miyoshi I, Kato M, Pasinelli P, Kasai N, Brown RH Jr, Itoyama Y. Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. (2001) J Neurosci., 21(23):9246-54.
- D. Trotti, M Aoki, P. Pasinelli, U Berger, R.H. Brown, Jr. and M. Hediger. Amyotrophic lateral sclerosis-linked glutamate transporter mutant has impaired uptake activity. (2001) J. Biol. Chem., 5;276(1):576-82.
- P.Pasinelli, M.K. Houseweart, R.H. Brown, Jr. and D.W. Cleveland. Caspase-1 and -3 are sequentially activated in familial amyotrophic lateral sclerosis. (2000) Proc. Acad. Natl. Sci., 97(25): 13901-13906.
- Ramakers G.M., Pasinelli P., van Beest M., van der Slot A., Gispen W.H. and De Graan P.N.E. Activation of pre- and postsynaptic protein kinase C during tetraethylammonium-induced long term potentiation in the CA1 field of the hippocampus. (2000) Neurosc. Lett., 286(1): 53-56.
- K.I. Lin, P. Pasinelli, R.H. Brown, Jr., J.M. Hardwick and R.R. Ratan. Decreased intracellular superoxide levels activate Sindbis virus-induced apoptosis: a role for reductive stress in modulating cell death. (1999) J. Biol. Chem., 274(19): 13650-13655.
- P. Pasinelli, D.R. Borchelt, M.K. Houseweart, D.W. Cleveland and R.H. Brown, Jr. Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase. (1998) Proc. Acad. Natl. Sci., 95: 15763-15768
- Edgar M.A., Pasinelli P., De Wit M., Anton B., Dokas L.A., Pastorino L., Di Luca M., Cattabeni F., Gispen W.H. and De Graan P.N.E. Phosphorylation of the casein kinase II domain of B-50 (GAP-43) in rat cortical growth cones. (1997) J. Neurochem., 69: 2206-221510.
- Ramakers G.M., Pasinelli P., Hens J.J., Gispen W.H. and De Graan P.N.
- Protein kinase C in synaptic plasticity: changes in the in situ phosphorylation state of identified pre- and postsynaptic substrates. (1997) Prog. Neuropsychopharmacol. Biol. Psychiatry, 21: 455-486.
- Pasinelli P., Ramakers G.M., Hens J.J., Oestreicher A.B., De Graan P.N.E. and Gispen W.H. Long-term potentiation and protein phosphorylation. (1995) Behav. Brain Res., 66: 53-59.
- Fedorov N.B., Pasinelli P., Oestreicher A.B., De Graan P.N.E. and Reymann K.G. Antibodies to postsynaptic PKC substrate neurogranin prevent long-term potentiation in hippocampal CA1 region. (1995) Eur. J. Neurosci., 7: 819-822.
- Ramakers G.M., De Graan P.N.E., Urban I.J., Kraay D., Tang T., Pasinelli P., Oestreicher A.B. and Gispen W.H. Temporal differences in the phosphorylation state of pre- and postsynaptic protein kinase C substrates B-50/GAP-43 and neurogranin during long-term potentiation. (1995) J. Biol. Chem., 270: 13892-13898.
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Individual Expertise profile of
Piera Pasinelli, Ph.D., Copyright © Piera Pasinelli, Ph.D..
Last Updated
by Admin
: Friday, September 25, 2009 9:11:15 AM
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