Matt Scaglione
Assistant Professor of Molecular Genetics and Microbiology
The Scaglione lab is interested in the regulation of protein homeostasis (proteostasis) in neurodegenerative diseases. We use a wide array of model systems including protein biochemistry, the social amoeba Dictyostelium discoideum
, human cell culture, and mouse models to understand cellular pathways that deal with misfolded proteins. The goal of our research is to understand pathways that deal with misfolded proteins and develop strategies to enchance these pathways. We hope this strategy will lead to the development of new therapies for neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), and the polyglutamine diseases.
Current Appointments & Affiliations
- Assistant Professor of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2019
Contact Information
- 5128 MSRB III, Durham, NC 27710
- 5128 MSRB III, Box 103853, Durham, NC 27710
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matt.scaglione@duke.edu
(919) 660-8830
- Background
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Education, Training, & Certifications
- Ph.D., Saint Louis University, School of Medicine 2001
- Research
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Selected Grants
- Novel chaperones and neurodegeneration awarded by National Institutes of Health 2019 - 2024
- Medical Scientist Training Program awarded by National Institutes of Health 1997 - 2022
- Defining the Mechanism of ubiquitin transfer by Ube2k awarded by BERG 2020 - 2022
- Training Program in Developmental and Stem Cell Biology awarded by National Institutes of Health 2001 - 2022
- Investigation into protein quality control pathways in Dictyostetlium discoideum awarded by National Institutes of Health 2016 - 2021
- Small molecule regulation of a protein quality control E3 to treat PSP awarded by CurePSP 2020 - 2021
- Defining the Mechanism of ubiquitin transfer by Ube2k awarded by BERG 2019 - 2020
- Analysis of a novel class of molecular chaperones that suppress polyglutamine aggregation awarded by Hereditary Disease Foundation 2019 - 2020
- Publications & Artistic Works
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Selected Publications
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Academic Articles
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Kanack, Adam, Vinayak Vittal, Holly Haver, Theodore Keppel, Rebekah L. Gundry, Rachel E. Klevit, and Kenneth Matthew Scaglione. “UbcH5 Interacts with Substrates to Participate in Lysine Selection with the E3 Ubiquitin Ligase CHIP.” Biochemistry 59, no. 22 (June 9, 2020): 2078–88. https://doi.org/10.1021/acs.biochem.0c00084.Full Text Link to Item
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Madrigal, Sabrina C., Zipporah McNeil, Rebekah Sanchez-Hodge, Chang-He Shi, Cam Patterson, Kenneth Matthew Scaglione, and Jonathan C. Schisler. “Changes in protein function underlie the disease spectrum in patients with CHIP mutations.” J Biol Chem 294, no. 50 (December 13, 2019): 19236–45. https://doi.org/10.1074/jbc.RA119.011173.Full Text Link to Item
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Santarriaga, Stephanie, Alicia Fikejs, Jamie Scaglione, and K Matthew Scaglione. “A Heat Shock Protein 48 (HSP48) Biomolecular Condensate Is Induced during Dictyostelium discoideum Development.” Msphere 4, no. 3 (June 19, 2019). https://doi.org/10.1128/mSphere.00314-19.Full Text Link to Item
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Santarriaga, Stephanie, Holly N. Haver, Adam J. Kanack, Alicia S. Fikejs, Samantha L. Sison, John M. Egner, Jonathan R. Bostrom, et al. “SRCP1 Conveys Resistance to Polyglutamine Aggregation.” Mol Cell 71, no. 2 (July 19, 2018): 216-228.e7. https://doi.org/10.1016/j.molcel.2018.07.008.Full Text Link to Item
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Kanack, Adam J., Oliver J. Newsom, and Kenneth Matthew Scaglione. “Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP.” J Biol Chem 293, no. 8 (February 23, 2018): 2735–43. https://doi.org/10.1074/jbc.RA117.000477.Full Text Link to Item
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Wang, Bo, Li Zeng, Sean A. Merillat, Svetlana Fischer, Joseph Ochaba, Leslie M. Thompson, Sami J. Barmada, Kenneth M. Scaglione, and Henry L. Paulson. “The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.” Neurobiol Dis 109, no. Pt A (January 2018): 127–36. https://doi.org/10.1016/j.nbd.2017.10.002.Full Text Link to Item
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Sutton, Joanna R., Jessica R. Blount, Kozeta Libohova, Wei-Ling Tsou, Gnanada S. Joshi, Henry L. Paulson, Maria do Carmo Costa, K Matthew Scaglione, and Sokol V. Todi. “Interaction of the polyglutamine protein ataxin-3 with Rad23 regulates toxicity in Drosophila models of Spinocerebellar Ataxia Type 3.” Hum Mol Genet 26, no. 8 (April 15, 2017): 1419–31. https://doi.org/10.1093/hmg/ddx039.Full Text Link to Item
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Lass, A., R. Cocklin, K. M. Scaglione, M. Skowyra, S. Korolev, M. Goebl, and D. Skowyra. “Erratum: The loop-less tmCdc34 E2 mutant defective polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2 [Cell Division, 6 (2011) 7], Doi: 10.1186/1747-1028-6-7.” Cell Division 11, no. 1 (October 6, 2016). https://doi.org/10.1186/s13008-016-0018-1.Full Text
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Ristic, Gorica, Wei-Ling Tsou, Ermal Guzi, Adam J. Kanack, Kenneth Matthew Scaglione, and Sokol V. Todi. “USP5 Is Dispensable for Monoubiquitin Maintenance in Drosophila.” J Biol Chem 291, no. 17 (April 22, 2016): 9161–72. https://doi.org/10.1074/jbc.M115.703504.Full Text Link to Item
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Wang, Bo, Sean A. Merillat, Michael Vincent, Amanda K. Huber, Venkatesha Basrur, Doris Mangelberger, Li Zeng, et al. “Loss of the Ubiquitin-conjugating Enzyme UBE2W Results in Susceptibility to Early Postnatal Lethality and Defects in Skin, Immune, and Male Reproductive Systems.” J Biol Chem 291, no. 6 (February 5, 2016): 3030–42. https://doi.org/10.1074/jbc.M115.676601.Full Text Link to Item
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Santarriaga, Stephanie, Amber Petersen, Kelechi Ndukwe, Anthony Brandt, Nashaat Gerges, Jamie Bruns Scaglione, and Kenneth Matthew Scaglione. “The Social Amoeba Dictyostelium discoideum Is Highly Resistant to Polyglutamine Aggregation.” J Biol Chem 290, no. 42 (October 16, 2015): 25571–78. https://doi.org/10.1074/jbc.M115.676247.Full Text Link to Item
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Zhang, Huaqun, Joseph Amick, Ritu Chakravarti, Stephanie Santarriaga, Simon Schlanger, Cameron McGlone, Michelle Dare, et al. “A bipartite interaction between Hsp70 and CHIP regulates ubiquitination of chaperoned client proteins.” Structure 23, no. 3 (March 3, 2015): 472–82. https://doi.org/10.1016/j.str.2015.01.003.Full Text Link to Item
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Faggiano, S., R. P. Menon, G. P. Kelly, S. V. Todi, K. M. Scaglione, P. V. Konarev, D. I. Svergun, H. L. Paulson, and A. Pastore. “Allosteric regulation of deubiquitylase activity through ubiquitination.” Frontiers in Molecular Biosciences 2, no. FEB (February 5, 2015). https://doi.org/10.3389/fmolb.2015.00002.Full Text
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Vittal, Vinayak, Lei Shi, Dawn M. Wenzel, K Matthew Scaglione, Emily D. Duncan, Venkatesha Basrur, Kojo S. J. Elenitoba-Johnson, et al. “Intrinsic disorder drives N-terminal ubiquitination by Ube2w.” Nat Chem Biol 11, no. 1 (January 2015): 83–89. https://doi.org/10.1038/nchembio.1700.Full Text Link to Item
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Blount, Jessica R., Wei-Ling Tsou, Gorica Ristic, Aaron A. Burr, Michelle Ouyang, Holland Galante, K Matthew Scaglione, and Sokol V. Todi. “Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23.” Nat Commun 5 (August 21, 2014): 4638. https://doi.org/10.1038/ncomms5638.Full Text Link to Item
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Tsou, W. L., A. A. Burr, M. Ouyang, J. R. Blount, K. M. Scaglione, and S. V. Todi. “Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo.” Journal of Biological Chemistry 288, no. 48 (November 29, 2013): 34460–69. https://doi.org/10.1074/jbc.M113.513903.Full Text
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Faggiano, S., R. P. Menon, G. P. Kelly, J. McCormick, S. V. Todi, K. M. Scaglione, H. L. Paulson, and A. Pastore. “Enzymatic production of mono-ubiquitinated proteins for structural studies: The example of the Josephin domain of ataxin-3.” Febs Open Bio 3 (November 11, 2013): 453–58. https://doi.org/10.1016/j.fob.2013.10.005.Full Text
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Blair, Laura J., Bryce A. Nordhues, Shannon E. Hill, K Matthew Scaglione, John C. O’Leary, Sarah N. Fontaine, Leonid Breydo, et al. “Accelerated neurodegeneration through chaperone-mediated oligomerization of tau.” J Clin Invest 123, no. 10 (October 2013): 4158–69. https://doi.org/10.1172/JCI69003.Full Text Link to Item
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Smith, Matthew C., K Matthew Scaglione, Victoria A. Assimon, Srikanth Patury, Andrea D. Thompson, Chad A. Dickey, Daniel R. Southworth, Henry L. Paulson, Jason E. Gestwicki, and Erik R. P. Zuiderweg. “The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex.” Biochemistry 52, no. 32 (August 13, 2013): 5354–64. https://doi.org/10.1021/bi4009209.Full Text Link to Item
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Scaglione, Kenneth Matthew, Venkatesha Basrur, Naila S. Ashraf, John R. Konen, Kojo S. J. Elenitoba-Johnson, Sokol V. Todi, and Henry L. Paulson. “The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates.” J Biol Chem 288, no. 26 (June 28, 2013): 18784–88. https://doi.org/10.1074/jbc.C113.477596.Full Text Link to Item
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Todd, Peter K., Seok Yoon Oh, Amy Krans, Fang He, Chantal Sellier, Michelle Frazer, Abigail J. Renoux, et al. “CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome.” Neuron 78, no. 3 (May 8, 2013): 440–55. https://doi.org/10.1016/j.neuron.2013.03.026.Full Text Link to Item
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Scaglione, K Matthew, Eszter Zavodszky, Sokol V. Todi, Srikanth Patury, Ping Xu, Edgardo Rodríguez-Lebrón, Svetlana Fischer, et al. “Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP.” Mol Cell 43, no. 4 (August 19, 2011): 599–612. https://doi.org/10.1016/j.molcel.2011.05.036.Full Text Link to Item
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Lass, A., R. Cocklin, K. M. Scaglione, M. Skowyra, S. Korolev, M. Goebl, and D. Skowyra. “The loop-less tm Cdc34 E2 mutant defective in polyubiquitination in vitro and in vivo supports yeast growth in a manner dependent on Ubp14 and Cka2.” Cell Division 6 (March 31, 2011). https://doi.org/10.1186/1747-1028-6-7.Full Text
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Todi, Sokol V., K Matthew Scaglione, Jessica R. Blount, Venkatesha Basrur, Kevin P. Conlon, Annalisa Pastore, Kojo Elenitoba-Johnson, and Henry L. Paulson. “Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117.” J Biol Chem 285, no. 50 (December 10, 2010): 39303–13. https://doi.org/10.1074/jbc.M110.181610.Full Text Link to Item
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Todi, Sokol V., Brett J. Winborn, K Matthew Scaglione, Jessica R. Blount, Sue M. Travis, and Henry L. Paulson. “Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3.” Embo J 28, no. 4 (February 18, 2009): 372–82. https://doi.org/10.1038/emboj.2008.289.Full Text Link to Item
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Winborn, Brett J., Sue M. Travis, Sokol V. Todi, K Matthew Scaglione, Ping Xu, Aislinn J. Williams, Robert E. Cohen, Junmin Peng, and Henry L. Paulson. “The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains.” J Biol Chem 283, no. 39 (September 26, 2008): 26436–43. https://doi.org/10.1074/jbc.M803692200.Full Text Link to Item
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Scaglione, K Matthew, Parmil K. Bansal, Andrew E. Deffenbaugh, Alexi Kiss, Johnnie M. Moore, Sergey Korolev, Ross Cocklin, Mark Goebl, Katsumi Kitagawa, and Dorota Skowyra. “SCF E3-mediated autoubiquitination negatively regulates activity of Cdc34 E2 but plays a nonessential role in the catalytic cycle in vitro and in vivo.” Mol Cell Biol 27, no. 16 (August 2007): 5860–70. https://doi.org/10.1128/MCB.01555-06.Full Text Link to Item
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Kim, Hyoung Tae, Kwang Pyo Kim, Fernando Lledias, Alexei F. Kisselev, K Matthew Scaglione, Dorota Skowyra, Steven P. Gygi, and Alfred L. Goldberg. “Certain pairs of ubiquitin-conjugating enzymes (E2s) and ubiquitin-protein ligases (E3s) synthesize nondegradable forked ubiquitin chains containing all possible isopeptide linkages.” J Biol Chem 282, no. 24 (June 15, 2007): 17375–86. https://doi.org/10.1074/jbc.M609659200.Full Text Link to Item
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Deffenbaugh, Andrew E., K Matthew Scaglione, Lingxiao Zhang, Johnnie M. Moore, Tione Buranda, Larry A. Sklar, and Dorota Skowyra. “Release of ubiquitin-charged Cdc34-S - Ub from the RING domain is essential for ubiquitination of the SCF(Cdc4)-bound substrate Sic1.” Cell 114, no. 5 (September 5, 2003): 611–22. https://doi.org/10.1016/s0092-8674(03)00641-x.Full Text Link to Item
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- Teaching & Mentoring
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Recent Courses
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