Maggie Panning Pearce, PhD
As our population has rapidly aged during the past century, age-related disorders such as neurodegenerative disease have become serious public health issues. Nearly all neurodegenerative diseases [e.g., Alzheimer’s disease, Parkinson’s disease, Huntington’s disease (HD), and amyotrophic lateral sclerosis] are associated with the conversion of a particular protein from its normally folded, native state into a misfolded state, leading to the formation of protein aggregates that have deleterious effects on neurons and glia. Accumulating evidence indicates that these protein aggregates can move between different regions of the brain in a prion-like manner — by transferring between individual cells and triggering the conversion of natively folded proteins in the new cells they encounter.
The major focus of our laboratory is to investigate how protein aggregates associated with inherited neurodegenerative diseases, such as HD, transfer between cells in an intact brain. Patients with HD inherit at least one mutant version of the huntingtin (Htt) gene containing an expanded CAG repeat region, producing Htt proteins with expanded polyglutamine stretches near their N-termini. This mutation causes the Htt protein to be highly aggregation-prone, and mutant Htt aggregates have recently been demonstrated to have prion-like properties. Dr. Panning Pearce's research uses cell biological techniques and powerful genetic tools available in the fruit fly (Drosophila melanogaster) to elucidate the molecular mechanisms that underlie prion-like transfer of pathogenic Htt aggregates in an in vivo setting.
- BSc in Biochemistry, Le Moyne College
- PhD in Pharmacology, SUNY Upstate Medical University
- Postdoctoral scholar, Stanford University
- Donnelly KM, DeLorenzo OR*, Zaya ADA, Pisano GE*, Thu W*, Luo L, Kopito RR, and Panning Pearce MM. "Phagocytic Glia Are Obligatory Intermediates in Transmission of Mutant Huntingtin Aggregates Across Neuronal Synapses." eLife 9:e58499 (2020).
- Van der Goot AT, Pearce MMP, Leto DE, Shaler TA, and Kopito RR. "Redundant and Antagonistic Roles of XTP3B and OS9 in Decoding Glycan and Non-glycan Degrons in ER-associated Degradation." Mol Cell 70(3): 516-30 (2018).
- Donnelly KM and Pearce MMP. "Monitoring Cell-to-cell Transmission of Prion-like Protein Aggregates in Drosophila Melanogaster." J Vis Exp, 133:e56906 (2018).
- Pearce MMP and Kopito RR. "Prion-like Characteristics of Polyglutamine-containing Proteins." Cold Spring Harb Perspect Med pii:a024257 (2018).
- Pearce MMP. "Prion-like Transmission of Pathogenic Protein Aggregates in Genetic Models of Neurodegenerative Disease." Curr Opin Gen Dev 44:149-55 (2017).
- Pearce, M.M.P., Spartz, E.J., Hong, W., Luo, L., and Kopito, R.R. "Prion-like Transmission of Neuronal Huntingtin Aggregates to Phagocytic Glia in the Drosophila Brain." Nat Commun 6, 6758 (2015)
- Tyler, R.E., Pearce, M.M.P., Shaler, T.A., Olzmann, J.A., Greenblatt, E.J., and Kopito, R.R. "Unassembled CD147 Is an Endogenous Endoplasmic Reticulum-associated Degradation Substrate." Mol Biol Cell 23(24), 4668-4678 (2012)
- Tsai, Y.C., Leichner, G.S., Pearce, M.M.P., Wilson, G.L., Wojcikiewicz, R.J.H., Roitelman, J., and Weissman, A.M. "Differential Regulation of HMG-CoA Reductase and Insig-1 by Enzymes of the Ubiquitin-proteasome System." Mol Biol Cell 23(24), 4484-4494 (2012)
- Trevino, R.S., Lauckner, J.E., Sourigues, Y., Pearce, M.M.P., Bousset, L., Melki, R., and Kopito, R.R. "Fibrillar Structure and Charge Determine the Interaction of Polyglutamine Protein Aggregates with the Cell Surface." J Biol Chem 287(35), 29722-29728 (2012)
- Lu, J.P., Wang, Y., Sliter, D.A., Pearce, M.M.P., and Wojcikiewicz, R.J.H. "RNF170 Protein, an Endoplasmic Reticulum Membrane Ubiquitin Ligase, Mediates Inositol 1,4,5-trisphosphate Receptor Ubiquitination and Degradation." J Biol Chem 286(27), 24426-24433 (2011)
- Wang, Y., Pearce, M.M.P., Sliter, D.A., Olzmann, J.A., Christianson, J.C., Kopito, R.R., Boeckmann, S., Gagen, C., Leichner, G.S., Roitelman, J., and Wojcikiewicz, R.J.H. "SPFH1 and SPFH2 Mediate the Ubiquitination and Degradation of Inositol 1,4,5-trisphosphate Receptors in Muscarinic Receptor-expressing HeLa Cells." Biochim Biophys Acta 1793(11), 1710-1718 (2009)
- Wojcikiewicz, R.J.H., Pearce, M.M.P., Sliter, D.A., and Wang, Y. "When Worlds Collide: IP3 Receptors and the ERAD Pathway." Cell Calcium 46(3), 147-153 (2009)
- Pearce, M.M.P., Wormer, D.B., Wilkens, S., and Wojcikiewicz, R.J.H. "An Endoplasmic Reticulum (ER) Membrane Complex Composed of SPFH1 and SPFH2 Mediates the ER-associated Degradation of Inositol 1,4,5-trisphosphate Receptors." J Biol Chem 284(16), 10433-10445 (2009)
- Pearce, M.M.P., Wang, Y., Kelley, G.G., and Wojcikiewicz, R.J.H. "SPFH2 Mediates the Endoplasmic Reticulum-associated Degradation of Inositol 1,4,5-trisphosphate Receptors and Other Substrates in Mammalian Cells." J Biol Chem 282(28), 20104-20115 (2007)
- Alzayady, K., Panning, M.M., Kelley, G.G., and Wojcikiewicz, R.J.H. "Involvement of the P97-Ufd1-Npl4 Complex in the Regulated Endoplasmic Reticulum-associated Degradation of Inositol 1,4,5-trisphosphate Receptors."J Biol Chem 280(41), 34530-34537 (2005)
- Panning, M.M. and Gilbert, D.M. "Spatio-temporal Organization of DNA Replication in Murine Embryonic Stem, Primary, and Immortalized Cells." J Cell Biochem 95(1), 74-82 (2005)
- Protein misfolding and aggregation
- Prion-like mechanisms underlying neurodegenerative disease
- Modeling genetic disease in the fruit fly (Drosophila melanogaster)
- Mentoring undergraduate and graduate students interested in doing laboratory research