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Meredith Jackrel was a Post-Doctoral Fellow and Research Associate in the lab from March 2010 to July 2017. She received her Ph.D. in Chemistry from Yale University in 2010 and graduated from the College of New Jersey with a BS in Chemistry in 2004. In 2011, Meredith won an American Heart Association Post-Doctoral Fellowship! In 2014, Meredith was selected as a finalist for the Regeneron Prize for Creative Innovation in a Postdoctoral Fellow and also won a Target ALS Springboard Fellowship. In 2017, Meredith went on to establish her own research program as an Assistant Professor in the Chemistry Department at Washington University in St. Louis.

Publications

March, Z.M., K. Sweeney°, H. Kim°, X. Yan°, L.M. Castellano, M.E. Jackrel, J. Lin, E. Chuang, E. Gomes, C. W. Willicott, K. Michalska, R. Jedrzejczak, A. Joachimiak, K.A. Caldwell, G.A. Caldwell, O. Shalem, and J. Shorter. (2020). Therapeutic genetic variation revealed in diverse Hsp104 homologs. eLife. 9:e57457. pdf file link (°Co-second author).

Mack, K.L.*, H. Kim*, M.E. Jackrel, J. Lin, J.E. DeNizio, X. Yan, E. Chuang, A. Tariq, R.R. Cupo, L.M. Castellano, K.A. Caldwell, G.A. Caldwell, and J. Shorter. (2020). Tuning Hsp104 specificity to selectively detoxify α-synuclein. BioRxiv. doi: 10.1101/2020.04.15.043935. pdf file link (*Co-first author.).

Tariq, A.*, J. Lin*, M.E. Jackrel*, C.D. Hesketh, P.J. Carman, K.L. Mack, R. Weitzman, C. Gambogi, O.A. Hernandez Murillo, E.A. Sweeny, E. Gurpinar, A.L. Yokom, S.N. Gates, K. Yee, S. Sudesh, J. Stillman, A.N. Rizo, D.R. Southworth, and J. Shorter. (2019). Mining disaggregase sequence space to safely counter TDP-43, FUS, and alpha-synuclein proteotoxicity. Cell Rep. 28(8):2080–2095. pdf file link (*Co-first author).

Ryan, J.J., M.L. Sprunger, K. Holthaus, J. Shorter^, and M.E. Jackrel^. (2019). Engineered protein disaggregases mitigate toxicity of aberrant prion-like fusion proteins underlying sarcoma. J. Biol. Chem. 294(29):11286–11296. pdf file link (^Co-corresponding author).

Durie, C.L., J. Lin, N.W. Scull, K.L. Mack, M.E. Jackrel, E.A. Sweeny, L.M. Castellano, J. Shorter, and A.L. Lucius. (2019). Hsp104 and potentiated variants can operate as distinct non-processive translocases. Biophys. J. 116(10):1856-1872. pdf file link

Michalska, K.*, K. Zhang*, Z.M. March*, C. Hatzos-Skintges, G. Pintilie, L. Bigelow, L.M. Castellano, L.J. Miles, M.E. Jackrel, E. Chuang, R. Jedrzejczak, J. Shorter, W. Chiu, and A. Joachimiak. (2019). Structure of Calcarisporiella thermophila Hsp104 disaggregase that antagonizes diverse proteotoxic misfolding events. Structure. 27(3):449-463. pdf file link (*Co-first author).

Guo, L.*, H.J. Kim*, H. Wang*, J. Monaghan°, F. Freyermuth°, J.C. Sung°, K. O’Donovan, C.M. Fare, Z. Diaz, N. Singh, Z.C. Zhang, M. Coughlin, E.A. Sweeny, M.E. DeSantis, M.E. Jackrel, C.B. Rodell, J.A. Burdick, O.D. King, A.D. Gitler, C. Lagier-Tourenne, U.B. Pandey, Y.M. Chook, J.P. Taylor, and J. Shorter. (2018). Nuclear-import receptors reverse aberrant phase transitions of RNA-binding proteins with prion-like domains. Cell. 173(3):677-692. pdf file link (*Co-first author. °Co-second author).

Tariq, A.*, J. Lin*, M.M. Noll*, M.P. Torrente, K.L. Mack, O. Hernandez Murillo, M.E. Jackrel, and J. Shorter. (2018). Potentiating Hsp104 activity via phosphomimetic mutations in the middle domain. FEMS Yeast Res. doi: 10.1093/femsyr/foy042. pdf file link (*Co-first author).

Gates, S.N*., A.L. Yokom*, J. Lin, M.E. Jackrel, A.N. Rizo, N.M. Kendsersky, C.E. Buell, E.A. Sweeny, K.L. Mack, E. Chuang, M.P. Torrente, M. Su, J. Shorter, and D.R. Southworth. (2017). Ratchet-like polypeptide translocation mechanism of the AAA+ disaggregase Hsp104. Science. 357(6348):273-279. pdf file link (*Co-first author).

Weaver, C.L., E.C. Duran, K.L. Mack, J. Lin, M.E. Jackrel, E.A. Sweeny, J. Shorter, and A.L. Lucius. (2017). Avidity for polypeptide binding by nucleotide-bound Hsp104 structures. Biochemistry. 56(15):2071–2075. pdf file link

Yasuda, K., S.F. Clatterbuck-Soper, M.E. Jackrel, J. Shorter, and S. Mili. (2017). Cytoplasmic FUS inclusions disrupt Kinesin-­1 leading to loss of detyrosinated microtubules and RNA mislocalization. J. Cell Biol. 216(4):1015-1034. pdf file link

Jackrel, M.E.^, and J. Shorter^. (2017). Protein-remodeling factors as potential therapeutics for neurodegenerative disease. Front. Neurosci. 11:99. pdf file link (^Co-corresponding author).

Yokom, A.L., S.N. Gates, M.E. Jackrel, K.L. Mack, M. Su, J. Shorter, and D.R. Southworth. (2016). Spiral architecture of the Hsp104 disaggregase reveals the basis for polypeptide translocation. Nat. Struct. Mol. Biol. 23(9):830-7. pdf file link

Torrente, M.P., E. Chuang, M.M. Noll, M.E. Jackrel, M.S. Go, and J. Shorter. (2016). Mechanistic insights into Hsp104 potentiation. J. Biol. Chem. 291(10):5101-5115. pdf file link

Jackrel, M.E., K. Yee, A. Tariq, A.I. Chen, and J. Shorter. (2015). Disparate mutations confer therapeutic gain of Hsp104 function. ACS Chem. Biol. 10(12):2672-9. pdf file link

Jackrel, M.E., and J. Shorter. (2015). Engineering enhanced protein disaggregases for neurodegenerative disease. Prion 9(2):90-109. pdf file link

Sweeny, E.A., M.E. Jackrel, M.S. Go, M.A. Sochor, B.M. Razzo, M.E. DeSantis, K. Gupta, and J. Shorter. (2015). The Hsp104 N-terminal domain enables disaggregase plasticity and potentiation. Mol. Cell. 57(5):836-849. pdf file link

Jackrel, M.E., A. Tariq, K. Yee, R. Weitzman, and J. Shorter. (2014). Isolating potentiated Hsp104 variants using yeast proteinopathy models. J. Vis. Exp. 93:e52089 doi:10.3791/52089. pdf file link

Jackrel, M.E., and J. Shorter. (2014). Potentiated Hsp104 variants suppress toxicity of diverse neurodegenerative disease-linked proteins. Dis. Model Mech. 7(10):1175-1184. pdf file link

Jackrel, M.E., and J. Shorter. (2014). Reversing deleterious protein aggregation with re-engineered protein disaggregases. Cell Cycle. 13(9):1379-1383. pdf file link

Jackrel, M.E., M.E. DeSantis, B.A. Martinez, L.M. Castellano, R.M. Stewart, K.A. Caldwell, G.A. Caldwell, and J. Shorter. (2014). Potentiated Hsp104 variants antagonize diverse proteotoxic misfolding events. Cell. 156:170–182. pdf file link

DeSantis, M.E., E.H. Leung, E.A. Sweeny, M.E. Jackrel, M. Cushman-Nick, A. Neuhaus-Follini, S. Vashist, M.A. Sochor, M.N. Knight, and J. Shorter. (2012). Operational Plasticity Enables Hsp104 to Disaggregate Diverse Amyloid and Non-Amyloid Clients. Cell. 151:778-793. pdf file link

Jackrel, M.E. and J. Shorter. (2011). Shock and awe: unleashing the heat shock response to treat Huntington disease. J. Clin. Invest. 121(8): 2972-2975. pdf file link

Jackrel, M.E., A.L. Cortajarena, T.Y. Liu and L.Regan. (2010). Screening libraries to identify proteins with desired binding activities using a split-GFP reassembly assay. ACS Chem Biol. 5 (6): 553–562. pdf file link

Jackrel, M.E., R. Valverde and L. Regan. (2009) Redesign of a protein - peptide interaction: characterization and applications. Protein Science. 18(4): 762-74. pdf file link

Champion, E.A., B.H. Lane, M.E. Jackrel, L.Regan and S.J. Baserga. (2008). A direct interaction between the Utp6 half-a-tetratricopeptide repeat domain and a specific peptide in Utp21 is essential for efficient pre-rRNA processing. Mol Cell Biol. 28(21): 6547-56. pdf file link

 

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Department of Biochemistry & Biophysics
p3
University of Pennsylvania