Margaret M.P. Pearce, PhD

Margaret Pearce, PhD

Margaret M.P. Pearce PhD

Associate Professor of Biology and Neuroscience


BSc, Biochemistry, Le Moyne College

PhD, Pharmacology, SUNY Upstate Medical University

Postdoctoral scholar, Stanford University

Research Interests

  • Protein misfolding and aggregation
  • Prion-like mechanisms underlying neurodegenerative disease
  • Modeling genetic disease in the fruit fly (Drosophila melanogaster)
  • I mentor undergraduate and graduate students interested in doing laboratory research.


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. Our 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.

Selected Scholarly Activity

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)

Contact Information

Office location: Office: STC, Room 378; Lab: STC, Room 361
Mailing address: Box #38
University of Sciences
600 South 43rd Street
Philadelphia, PA 19104-4495

m [dot] pearce [at] usciences [dot] edu