<p>Guerriero, C.J. and J.L. Brodsky. The HERCulean
Guerriero, C.J. and J.L. Brodsky. The HERCulean task of recognizing, ubiquitinating, and shielding misfolded integral membrane proteins. J. Cell Biol. (2024) 223: e202405160
Contact
Office: (412) 624-4831
Lab: (412) 624-4830
A320 Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260
Our work focuses on understanding how misfolded proteins are recognized and destroyed in the cell, how molecular chaperones mediate protein quality control “decisions”, how cellular stress impacts protein homeostasis ("proteostasis"), and how defects in protein architecture can be corrected. Our early work contributed to the discovery of the endoplasmic reticulum associated degradation (ERAD) pathway, which we named, and ongoing studies are deciphering the mechanisms underlying this pathway in yeast, mammalian cell culture, and rodent models. The importance of ERAD is evidenced by the fact that >70 human diseases are associated with the pathway, and numerous ERAD substrates play vital roles in human physiology. To determine the molecular basis of these diseases and other protein conformational diseases, we express specific protein substrates in yeast, tissue culture, and rodent models, and characterize factors mediating their folding and disposal--and concomitant stress responses--using genetic, biochemical, cellular, and pharmacological tools. In parallel, biochemical assays are being developed in which distinct steps during ERAD and protein biogenesis can be reconstituted. New classes of small molecule modulators of chaperones and the ubiquitin-proteasome pathway have also been isolated and show efficacy in a range of disease models.
- Teresa Buck, Research Associate Professor
- Rahul Chauhan, Undergraduate Researcher
- Ruth Claycomb, Graduate Student
- Jennifer Goeckeler-Fried, Lab Manager and Research Specialist
- Chris Guerriero, Research Assistant Professor
- Anuradha Iyer, Graduate Student
- Aidan Porter, Pediatric Resident/Research Fellow
- Katherine Sharp, Graduate Student
- Shreya Tripathi, Undergraduate Researcher
- Hannah Vorndran, Research Assistant
- Morgan Webb, Graduate Student
<p>Kok, M. and J.L. Brodsky. The biogenesis of pot
Kok, M. and J.L. Brodsky. The biogenesis of potassium transporters: implications of disease-associated mutations. Crit. Rev. Biochem. Mol. Biol. (2024) In press
<p>Mann, M.J., C. Melendez-Suchi, M. Sukhoplyasova
Mann, M.J., C. Melendez-Suchi, M. Sukhoplyasova, A.R. Flory, M.C. Irvine, A.R. Iyer, H. Vorndran, C.J. Gueriero, J.L. Brodsky, L.M. Hendershot, and T.M. Buck. Loss of GRP170 results in catastrophic disruption of Endoplasmic Reticulum function. Mol. Biol. Cell (2024) 35(4):ar59
<p>Nguyen, N.H., S. Sheng, A. Banerjee, J. Chen, X
Nguyen, N.H., S. Sheng, A. Banerjee, J. Chen, X. Wang, T.D. Mackie, P.A. Welling, T.R. Kleyman, I. Bahar, A.E. Carlson, and J.L. Brodsky. Characterization of hyperactive mutations in the renal potassium channel ROMK uncovers unique effects on channel biogenesis and ion conductance. Mol. Biol. Cell (2024), In press
<p>Oppenheimer, K.G., N.A. Hager, C.K. McAtee, E.
Oppenheimer, K.G., N.A. Hager, C.K. McAtee, E. Filiztekin, C. Shang, J.A. Warnick, M.P. Bruchez, J.L. Brodsky, D.C. Prosser, A.V. Kwiatkowski and A.F. O’Donnell. A new series of fluorogen-activating proteins for quantitative protein trafficking and co-localization studies in S. cerevisiae. Mol. Biol. Cell (2024) 35: 35(7):mr5
<p>Nguyen, N.H., S. Sarangi, E.M. McChesney, S. Sh
Nguyen, N.H., S. Sarangi, E.M. McChesney, S. Sheng, J.D. Durrant, A.W. Porter, T.R. Kleyman, Z.W. Pitluk, and J.L. Brodsky. Genome mining yields new disease-associated ROMK variants with distinct defects. PLoS Genetics (2023) 19:e1011051
<p>Hendershot, L.M., T.M. Buck, and J.L. Brodsky.
Hendershot, L.M., T.M. Buck, and J.L. Brodsky. The essential functions of molecular chaperones and folding enzymes in maintaining endoplasmic reticulum homeostasis. J. Mol. Biol. (2024) In press
<p>Kok, M., K. Hartnett-Scott, C.L. Happe, M.L. Ma
Kok, M., K. Hartnett-Scott, C.L. Happe, M.L. MacDonald, E. Aizenman, J.L. Brodsky. The expression system influences the stability, maturation efficiency, and oligomeric properties of the potassium-chloride co-transporter-2, KCC2. Neurochem. Intl. (2024) 174: 105695
<p>Daskivich, G.J. and J.L. Brodsky. The generatio
Daskivich, G.J. and J.L. Brodsky. The generation of detergent-insoluble clipped fragments from an ERAD substrate in mammalian cells. Sci. Rep. (2023) 13:21508.
<p>Sukhoplyasova, M., A. Keith, E. Perrault, A.S.
Sukhoplyasova, M., A. Keith, E. Perrault, A.S. Jordahl, M.E. Yates, A. Pastor, Z. Li1, M. Freaney, R. Deshpande, D. Adams, C.J. Guerriero, S. Shi, O.B. Kashlan, T.R. Kleyman, J.L. Brodsky, and T.M. Buck. Lhs1 dependent ERAD is determined by transmembrane domain contacts. Biochem. J. (2023) 480: 1459-1473
<p>DeGiosio, R.A., Needham, P.G., Andrews, O.A., H
DeGiosio, R.A., Needham, P.G., Andrews, O.A., H. Tristan, Grubisha, M.J., Brodsky J.L., Camacho, C., and Sweet, R.A. Differential regulation of MAP2 by phosphorylation events in proline-rich versus C-terminal domains. FASEB J. (2023) 37: e23194
<p>Bhatia, T.N., A.S. Jamenis, M. Abbas, R.N. Clar
Bhatia, T.N., A.S. Jamenis, M. Abbas, R.N. Clark, K.M. Miner, M.N. Chandwani, R.E. Kim, W. Hilinski, L.A. O’Donnell, K.C. Luk, Y. Shi, X. Hu, J. Chen, J.L. Brodsky, and R.K. Leak. A 14-Day Pulse of PLX5622 Modifies α-Synucleinopathy in Preformed Fibril-Infused Aged Mice of Both Sexes. Neurobiol. Disease (2023) 184: 106196
<p>Marszalek, J., P. De Los Rio, D. Cyr, M.P. Maye
Marszalek, J., P. De Los Rio, D. Cyr, M.P. Mayer, V. Adupa, C. Andréasson, G. L. Blatch, J. Braun, J.L. Brodsky, B. Bukau, J.P. Chapple, C. Conz, S. Dementin, P. Genevaux, O. Genest, P. Goloubinoff, J. Gestwicki, C. Hammond, J.K. Hines, K. Ishikawa, L. Joachimiak, J. Kirstein, K. Liberek, D. Mokranjac, N. Nillegoda, C. Ramos, M. Rebeaud, D. Ron, S. Rospert, C. Sahi, R. Shalgi, B. Tomiczek, R. Ushioda, E. Ustyantseva, Y. Ye, M. Zylicz, and H. H. Kampinga. J-domain proteins: from molecular mechanisms to diseases. Cell Stress Chaper. (2023) 29: 21-33
<p>Oosten-Hawle, P., S.J. Backe, A. Ben-Zvi, D. Bo
Oosten-Hawle, P., S.J. Backe, A. Ben-Zvi, D. Bourboulia, M. Brancaccio, J. Brodsky, M. Clark, G. Colombo, M.B Cox, P. De Los Rios, F. Echtenkamp, A. Edkins, B. Freeman, P. Goloubinoff, W. Houry, J. Johnson, P. LaPointe, W. Li, V. Mezger, L. Neckers, N.B. Nillegoda, V. Prahlad, A. Reitzel, R. Scherz-Shouval, L. Sistonen, F.T.F. Tsai, M.R. Woodford, M. Mollapour, A.W. Truman. Second Virtual International Symposium on Cellular and Organismal Stress Responses, September 8-9, 2022. Cell Stress Chap. (2023) 28: 1-9
Nguyen, N.H. and J.L. Brodsky. The cellular pathwa
Nguyen, N.H. and J.L. Brodsky. The cellular pathways that maintain the quality control and transport of diverse potassium channels. Biochim. Biophys. Acta (2023) 1866: 194908
Farinha, C.M., J.L. Brodsky, and N. Pedemonte. Fun
Farinha, C.M., J.L. Brodsky, and N. Pedemonte. Fundamental and translational research in cystic fibrosis—why we still need it. J. Cyst. Fibr. (2023) 22: S1-S4
Shao, H., S. Taguwa, L. Gilbert, A. Shkedi, S. San
Shao, H., S. Taguwa, L. Gilbert, A. Shkedi, S. Sannino, C.J. Guerriero, Z.T. Young, J.L. Brodsky, J.S. Weissman, J.E. Gestwicki, and J. Frydman. A campaign targeting a conserved Hsp70 site uncovers how subcellular localization is linked to distinct biological activities. Cell Chem. Biol. (2022) 29: 1303-1316
Brodsky J.L., D.M. Engleman, L.M. Hendershot, S. P
Brodsky J.L., D.M. Engleman, L.M. Hendershot, S. Piana-Agostinetti, and T. Sommer. Taking out the trash: How misfolded proteins are removed from the endoplasmic reticulum. Fac. Rev. (2022) 11: 29
Porter, A.W., J.L. Brodsky, and T.M. Buck. Emergin
Porter, A.W., J.L. Brodsky, and T.M. Buck. Emerging Links Between Endoplasmic Reticulum Stress Responses and Acute Kidney Injury. Am. J. Physiol-Cell Physiol. (2022) 323: C1697-C1703
Nakatsukasa, K., S. Wigge, Y. Takano, T. Kawarasak
Nakatsukasa, K., S. Wigge, Y. Takano, T. Kawarasaki, T. Kamura, and J.L. Brodsky. A positive genetic selection for transmembrane domain mutations in HRD1 underscores the importance of Hrd1 complex integrity during ERAD. Curr. Genet. (2022) 68: 227-242
Porter, A., D.N. Nguyen, D. Clayton, W.G. Ruiz, S.
Porter, A., D.N. Nguyen, D. Clayton, W.G. Ruiz, S.M. Mutchler, E.C. Ray, A.L. Marciszyn, L.J. Nkashama, A.R. Subramanya, S. Gingras, T.R. Kleyman, G. Apodaca, L.M. Hendershot, J.L. Brodsky, and T.M. Buck. The GRP170 molecular chaperone protects against renal tubule damage, ER stress, and acute kidney injury. JCI Insight (2022) 7: e151869
Galvin, J., E. Curran, F. Arteaga, A. Goossens, N.
Galvin, J., E. Curran, F. Arteaga, A. Goossens, N. Aubuchon-Endsley, M.A. McMurray, J. Moore, K.C. Hansen, H. Chial, H. Potter, J.L. Brodsky, and C.M. Coughlan. Proteasome activity modulates amyloid toxicity. FEMS Yeast Res. (2022) 22: 1-13
Kumari, D., E.A. Fisher, and J.L. Brodsky. Hsp4
Kumari, D., E.A. Fisher, and J.L. Brodsky. Hsp40s play distinct roles during the initial stages of apolipoprotein B biogenesis. Mol. Biol. Cell (2022) 33: 1-15
Needham, P.J., C.A. Bertrand, J.L. Goeckeler-Fr
Needham, P.J., C.A. Bertrand, J.L. Goeckeler-Fried, C. Zhang, Z. Sun, A.R. Wetzel, and J.L. Brodsky. SLC6A9 is selected for endoplasmic reticulum associated degradation (ERAD) due to Hsp70-dependent targeting of the STAS domain. Biochem. J. (2021) 478: 4203-4220
Bhatia, T.N., R.N. Clark, P.G. Needham, K.M. Mi
Bhatia, T.N., R.N. Clark, P.G. Needham, K.M. Miner, A.S. Jamenis, E.A. Eckhoff, N. Abraham, X. Hu, P. Wipf, K.C. Luk, J.L. Brodsky, and R.K. Leak. Heat Shock Protein 70 as a Sex-Skewed Regulator of α-Synucleinopathy. Neurotherapetics (2021) 18: 2541-2564
Shi, S., T.M. Buck, A.J. Nickerson, J.L. Brodsk
Shi, S., T.M. Buck, A.J. Nickerson, J.L. Brodsky, and T.R. Kleyman. Paraoxonase 2 is an ER chaperone that regulates expression of the epithelial sodium channel, ENaC. Am. J. Phys. Cell Physiol. (2022) 322: C111-C121
Sun, Z., C.J. Guerriero, and J.L. Brodsky. Substra
Sun, Z., C.J. Guerriero, and J.L. Brodsky. Substrate Ubiquitination Retains Misfolded Membrane Proteins in the Endoplasmic Reticulum for Degradation. Cell Rep. (2021) 36: 109717
Burns, G.D., O. Hillal, Z. Sun, K.R. Reutter, G.M.
Burns, G.D., O. Hillal, Z. Sun, K.R. Reutter, G.M. Preston, A.A. Augustine, J.L. Brodsky, and C.J. Guerriero. The characterization of distinct classes of misfolded proteins uncovers differential effects in yeast compromised for proteasome function. FEBS Lettr. (2021) 595: 2383–2394
Kumari, D. and J.L. Brodsky. The targeting of nati
Kumari, D. and J.L. Brodsky. The targeting of native proteins to the Endoplasmic Reticulum Associated Degradation (ERAD) pathway: An expanding repertoire of regulated substrates. Biomolecules (2021) 11: 1185
Sannino, S., M.E. Yates, M.E. Schurdak, S. Oesterr
Sannino, S., M.E. Yates, M.E. Schurdak, S. Oesterreich, A.V. Lee, P. Wipf, and J.L. Brodsky. Unique integrated stress response sensors regulate cancer cell susceptibility when Hsp70 activity is compromised. eLife (2021) 10: e64977
Ferro-Novick, S., F. Reggiori, and J. L. Brodsky.
Ferro-Novick, S., F. Reggiori, and J. L. Brodsky. ER-phagy, ER homeostasis and ER quality control: implications for disease and beyond. Trends Biochem. Sci. (2021) 46: 630-639.
Rastelli, E.J., S. Sannino, D.J. Hart, E.R. Sharlo
Rastelli, E.J., S. Sannino, D.J. Hart, E.R. Sharlow, J.S. Lazo, J.L. Brodsky, and P. Wipf. Synthesis and Evaluation of Bifunctional PTP4A Phosphatase Inhibitors Activating the ER Stress Pathway. Bioorg. Med. Chem. Lettr. (2021) 46: 128167
Goeckeler-Fried, J.L., R.A. Denny, D. Joshi, C. Hi
Goeckeler-Fried, J.L., R.A. Denny, D. Joshi, C. Hill, M.B. Larsen, A.N. Chiang, R.A. Frizzell, P. Wipf, E.J. Sorscher, and J.L. Brodsky. Improved correction of F508del-CFTR biogenesis with a folding facilitator and an inhibitor of protein ubiquitination. Bioorg. Med. Chem. Lettr. (2021) 48: 128243
Honer, J., K.M. Niemeyer, C. Fercher, A.L. Diez
Honer, J., K.M. Niemeyer, C. Fercher, A.L. Diez Tissera, N. Jaberolansar, Y. Jafrani, C. Zhou, J.J. Caramelo, A.M. Shewan, B.L. Schulz, J.L. Brodsky, and L.F. Zacchi. TorsinA folding and N-linked glycosylation are sensitive to redox homeostasis. Biochim. Biophys. Acta Mol. Cell. Res. (2021) 1868: 119073
Buck, T.M., X. Zeng, P.S. Cantrell, R.T. Cattley,
Buck, T.M., X. Zeng, P.S. Cantrell, R.T. Cattley, Z. Hasanbasri, M.E. Yates, D. Nguyen, N.A. Yates, and J.L. Brodsky. The Capture of a Disabled Proteasome Identifies Erg25 as a Substrate for Endoplasmic Reticulum Associated Degradation. Mol. Cell. Proteomics (2020) 19: 1896-1909
Estabrooks, S.E. and J.L. Brodsky. Recapitulation
Estabrooks, S.E. and J.L. Brodsky. Recapitulation disease-causing CFTR variant ubiquitination in isolated membranes. Analytic. Biochem. (2020) 604: 113829
Singh, A., N. Vashistha, J. Heck, X. Tang, P. Wipf
Singh, A., N. Vashistha, J. Heck, X. Tang, P. Wipf, J.L. Brodsky and R.Y. Hampton. Direct involvement of Hsp70 ATP hydrolysis in Ubr1-mediated quality control. Mol. Biol. Cell (2020) 31: 2669-2686
Ponzoni, L., N. H. Nguyen, I. Bahar, and J.L. Brod
Ponzoni, L., N. H. Nguyen, I. Bahar, and J.L. Brodsky. Complementary computational and experimental evaluation of missense variants in the ROMK potassium channel. PLoS Comp. Biol. (2020) 16(4):e1007749.
Terrab, L., C.J. Rosenker, L. Johnstone, L.K. Ngo,
Terrab, L., C.J. Rosenker, L. Johnstone, L.K. Ngo, L. Zhang, N.F. Ware, B. Miller, A.C. Topacio, S. Sannino, J.L. Brodsky, and P. Wipf. Synthesis and Selective Functionalization of Thiadiazine 1,1-Dioxides with Efficacy in a Model of Huntington’s Disease. ACS Med. Chem. Lett. (2020) 11:984-990.
Estabrooks, S.K. and J.L. Brodsky. Regulation of C
Estabrooks, S.K. and J.L. Brodsky. Regulation of CFTR biogenesis by the proteostatic network and pharmacological modulators. Int. J. Mol. Sci. (2020) 21: 452 doi:10.3390/ijms21020452
Betegon, M. and J.L. Brodsky. Unlocking the door f
Betegon, M. and J.L. Brodsky. Unlocking the door for ERAD. Nature Cell Biol. (2020) 22: 263-265
Sun, Z. and J.L. Brodsky. Protein quality contr
Sun, Z. and J.L. Brodsky. Protein quality control in the secretory pathway. J. Cell Biol. (2019) 218: 3171-3187
Guerriero, C.J., Y.K. Gomez, G.J. Daskivich, A.
Guerriero, C.J., Y.K. Gomez, G.J. Daskivich, A.A. Augustine, K.F. Weiberth, K. Nakatsukasa, M. Grabe, and J.L. Brodsky Harmonizing experimental data with modeling to predict membrane protein insertion in yeast. Biophys. J., (2019) 117: 668-678.
Cui, Y., S. Parashar, M. Zahoor, P.G. Needham, M.
Cui, Y., S. Parashar, M. Zahoor, P.G. Needham, M. Mari, M. Zhu, S. Chen, F. Reggiori, H. Farhan, J.L. Brodsky, and S. Ferro-Novick. A COPII subunit acts with an autophagy receptor to target endoplasmic reticulum for degradation. Science (2019) 365: 53-60
Needham, P.G., C. J. Guerriero, and J. L. Brods
Needham, P.G., C. J. Guerriero, and J. L. Brodsky. Chaperoning Endoplasmic Reticulum Associated Degradation (ERAD) and Protein Conformational Diseases, in “Cold Spring Harbor Perspectives in Biology: Protein Homeostasis” (2019) 11(8). pii: a033928.
Doonan*, L.M., C.J. Guerriero*, G.M. Preston*,
Doonan*, L.M., C.J. Guerriero*, G.M. Preston*, T.M. Buck, N. Khazanov, E.A. Fisher, H. Senderowitz, and J.L. Brodsky. Hsp104 Facilitates the Endoplasmic Reticulum Associated Degradation of Aggregation-Prone Substrates in Yeast. Protein Sci. (2019) 28: 1290-1306
Zaman, K., J. Knight, F. Hussain, R. Cao, S.K.
Zaman, K., J. Knight, F. Hussain, R. Cao, S.K. Estabrooks, G. Altawallbeh, K. Holloway, A. Jafrii, V. Sawczak, Y. Li, P. Getsy, F. Sun, T. Raffay, C. Cotton, J.L. Brodsky, A. Periasamy, S.J. Lewis, and B. Gaston. S-Nitrosylation of CHIP Enhances F508del CFTR Maturation. Am. J. Resp. Cell Mol. Biol. (2019) 61: 765-775
Werner, H.M., S.K. Estabrooks, G.M. Preston, J.
Werner, H.M., S.K. Estabrooks, G.M. Preston, J.L. Brodsky, and W.S. Horne. Exploring the Functional Consequences of Protein Backbone Alteration in Ubiquitin through Native Chemical Ligation. ChemBioChem (2019) 20: 2346-2350.
Mann, J.R., A.M. Gleixner, J.C. Mauna, E. Gomes, M
Mann, J.R., A.M. Gleixner, J.C. Mauna, E. Gomes, M.R. DeChellis-Marks, P.G. Needham, K.E. Copley, B. Hurtle, N.J. Pyles, B. Portz, C.B. Calder, Z.P. Wills, U.B. Pandey, J.K. Kofler, J.L. Brodsky, A. Thathiah, J. Shorter, and C.J. Donnelly. RNA-binding antagonizes neurotoxic phase transitions of TDP-43. Neuron (2019) 102: 321-338.
Chiang, A.N., M. Liang, A. Dominguez-Meijide, C
Chiang, A.N., M. Liang, A. Dominguez-Meijide, C. Masaracchia, C.S. Mazzone, D.W. Newhouse, N.M. Kendsersky, M.E. Yates, A. Manos-Turvey, P.G. Needham, J.L. Goeckeler, T.F. Outeiro, P. Wipf, and J.L. Brodsky. Synthesis and Evaluation of Esterified Hsp70 Agonists in Cellular Models of Protein Aggregation and Folding. Bioorg. Med. Chem. (2019) 27(1):79-91.
Pabon, N.A., Y. Xia, S. Estabrooks, Z. Ye, A.K. He
Pabon, N.A., Y. Xia, S. Estabrooks, Z. Ye, A.K. Herbrand, E. Süß, R.M. Biondi, V.A. Assimon, J.E. Gestwicki, J.L. Brodsky, C.J. Camacho, and Z. Bar-Joseph. Proteome-scale detection of small-molecule protein interactions using data from gene expression perturbations. PLoS Comp. Biol. (2018) 14(12):e1006651
Sheng, S., J. Chen, A. Mukherjee, M.E. Yates, T
Sheng, S., J. Chen, A. Mukherjee, M.E. Yates, T.M. Buck, J.L. Brodsky, M.A. Tolino, R.P. Hughey, and T.R. Kleyman Multifunctional thumb domain of the epithelial Na+ channel. J. Biol. Chem. (2018) 293: 17582-17592
Sannino, S., C.J. Guerriero, A.J. Sabnis, D. Be
Sannino, S., C.J. Guerriero, A.J. Sabnis, D. Beer-Stolz, C.T. Wallace, S.C. Watkins, T.G. Bivona, and J.L. Brodsky. Select compensatory quality control pathways play an essential role in cancer cell survival after Hsp70 inhibition. J. Cell Sci. (2018) 131(17). pii: jcs217760.
Buck, T.M. and J. L. Brodsky. Epithelial Sodium
Buck, T.M. and J. L. Brodsky. Epithelial Sodium Channel Biogenesis and Quality Control in the Early Secretory Pathway. Curr. Opin. Nephrol. Hypertens. (2018) 27:364-372
Mackie, T.D. and J.L. Brodsky. Investigating Po
Mackie, T.D. and J.L. Brodsky. Investigating Potassium Channels In Budding Yeast: A Genetic Sandbox. Genetics (2018) 209:637-650
Sun, Z. and J.L. Brodsky. The Degradation Pathw
Sun, Z. and J.L. Brodsky. The Degradation Pathway of a Model Misfolded Protein is Determined by Aggregation Propensity. Mol. Biol. Cell (2018) 29:1422-1434
Joshi, S., T. Wang, T.L.S. Araujo, S. Sharma, J
Joshi, S., T. Wang, T.L.S. Araujo, S. Sharma, J.L. Brodsky, and G. Chiosis. Adapting to stress – chaperome networks in cancer. Nature Rev. Cancer (2018) 18:562-575
Shurtleff, M.J., Itzhak, D.N., Schirle-Oakdale,
Shurtleff, M.J., Itzhak, D.N., Schirle-Oakdale, N.T., Hussmann, J.A., Weizebahn, J., Jonikas, M.C., Costa, E.A., Popova, K.D., Jan, C.H., Sinitcyn, P., Vembar, S.S., Hernandez, H., Cox, J., Burlingame, A., Brodsky, J.L., Frost, A., Borner, G.H.H., and Weissman, J.S. The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins. eLife (2018) 7. pii: e37018
Hager, N.A., C.J. Krasowski, T.D. Mackie, A.R.
Hager, N.A., C.J. Krasowski, T.D. Mackie, A.R. Kolb, P.G. Needham, A.A. Augustine, A. Dempsey, C. Szent-Gyorgyi, M.P. Bruchez, D.J. Bain, A.V. Kwiatkowski, A.F. O’Donnell and J.L. Brodsky. Select α-arrestins control surface abundance of the mammalian Kir2.1 potassium channel in a yeast model. J. Biol. Chem. (2018) 293:11006-11021
Preston, G.M., C.J. Guerriero, M.B. Metzger, S.
Preston, G.M., C.J. Guerriero, M.B. Metzger, S. Michaelis, and J.L. Brodsky. Substrate Insolubility Dictates Hsp104-Dependent Endoplasmic Reticulum Associated Degradation. Mol. Cell (2018) 70(2):242-253.e6
Doonan, L., E.A. Fisher, and J.L. Brodsky. Can
Doonan, L., E.A. Fisher, and J.L. Brodsky. Can modulators of Apolipoprotein B biogenesis serve as an alternate target for cholesterol-lowering drugs? Biochim. Biophys. Acta (2018) 1863(7):762-771
Mackie, T.D., B.Y. Kim, A.R. Subramanya, D.J. B
Mackie, T.D., B.Y. Kim, A.R. Subramanya, D.J. Bain, A.F. O’Donnell, P.A. Welling, and J.L. Brodsky. The endosomal trafficking factors CORVET and ESCRT suppress plasma membrane residence of the renal outer medullary potassium channel (ROMK). J. Biol. Chem. (2018) 293: 3201-3217
Amengual, J., L. Guo, A. Strong, J. Madrigal-Ma
Amengual, J., L. Guo, A. Strong, J. Madrigal-Matute, H. Zhang, S. Kaushik, J.L. Brodsky, D.J. Rader, A.M. Cuervo, and E.A. Fisher. Autophagy is required for sortilin-mediated degradation of apolipoprotein B100. Circul. Res. (2018) 122:568-582
Kashlan, O.B., C.L. Kinlough, M.M. Myerburg, S.
Kashlan, O.B., C.L. Kinlough, M.M. Myerburg, S. Shi, J. Chen, B.M. Blobner, T.M. Buck, J.L. Brodsky, R.R. Hughey, and T.R. Kleyman. N-linked Glycans are Required on Distinct Subunits for Epithelial Na+ Channel Maturation and Expression. Am. J. Physiol. Renal Physiol. (2018) 314: F483-F492
Sun, Z. and J.L. Brodsky. Guardians of th
Sun, Z. and J.L. Brodsky. Guardians of the ERAD Galaxy. Cell (2017) 171:267-268.
Sannino, S. and J.L. Brodsky. Targeting p
Sannino, S. and J.L. Brodsky. Targeting protein quality control pathways in breast cancer. BMC Biol. (2017) 15(1):109.
Nakasone, M.A., T.A. Lewis, O. Walker, A. Thaku
Nakasone, M.A., T.A. Lewis, O. Walker, A. Thakur, W. Mansour, C.A. Castañeda, J.L. Goeckeler, F. Parlati, T.-F. Chou, O. Hayat, U.K. Nowicka, S. Krueger, S.L. Schreiber, M.H. Glickman, J.L. Brodsky, R.J. Deshaies, and D. Fushman. Structural basis for the inhibitory effect of ubistatins. Structure (2017) 25(12):1839-1855
Gleixner, A.M., D.F. Hutchinson, S. Sannino, T.
Gleixner, A.M., D.F. Hutchinson, S. Sannino, T.N. Bhatia, L.C Leak, P.T. Flaherty, P. Wipf, J.L. Brodsky, and R.K. Leak. N-acetyl-L-cysteine protects astrocytes against proteotoxicity without recourse to glutathione. Mol. Pharm. (2017) 92:564-575.
Shi, S., T.M. Buck, C.L. Kinlough, A.L. Marcisz
Shi, S., T.M. Buck, C.L. Kinlough, A.L. Marciszyn, R.P. Hughey, M. Chalfie, J.L. Brodsky and T.R. Kleyman. Regulation of the Epithelial Na+ Channel by Paraoxonase-2. J. Biol. Chem. 292:15927-15938.
Zacchi, L.F., J.C. Dittmar, M.J. Mihalevic, A.
Zacchi, L.F., J.C. Dittmar, M.J. Mihalevic, A. Shewan, B.L. Schulz, J.L. Brodsky, and K.A. Bernstein. A novel high-throughput yeast genetic screen for factors modifying protein levels of the Early-Onset Torsion Dystonia-associated variant torsinADE. Dis. Mod. Mech. (2017) 10: 1129-1140
O'Donnell, B.M., T.D. Mackie, and J.L. Brodsky.
O'Donnell, B.M., T.D. Mackie, and J.L. Brodsky. Linking channelopathies with endoplasmic reticulum associated degradation. Channels (2017) 11: 499-501
O’Donnell, B.M., T.D. Mackie, A.R. Subramanya,
O’Donnell, B.M., T.D. Mackie, A.R. Subramanya, and J.L. Brodsky. Endoplasmic Reticulum Associated Degradation of the Renal Outer Medullary Potassium Channel, ROMK, Underlies Type II Bartter Syndrome. J. Biol. Chem. (2017) 292:12813-12827
Guerriero, C.J., K. Reutter, A.A. Augustine, G.
Guerriero, C.J., K. Reutter, A.A. Augustine, G.M. Preston, K.F. Weiberth, T.D. Mackie, H.C. Cleveland, N.P. Bethel, K.M. Callenberg, K. Nakatsukasa, M. Grabe, and J.L. Brodsky. Energetic barriers to the retrotranslocation of integral membrane ERAD substrates. Mol. Biol. Cell (2017) 28:2076-2090
Ye, Z., P.G. Needham, S.K. Estabrooks, S.K. Whi
Ye, Z., P.G. Needham, S.K. Estabrooks, S.K. Whitaker, B.L. Garcia, S. Misra, J.L. Brodsky, and C.J. Camacho. Symmetry breaking during homodimeric assembly kinetically activates an E3 ubiquitin ligase. Sci. Rep. (2017) 7: 1789
Braganza, A., J. Li, X. Zeng, N. Yates, N.B. De
Braganza, A., J. Li, X. Zeng, N. Yates, N.B. Dey, J. Andrews, J. Clark, X.-H. Wang, C. St. Croix, R. O’Sullivan, L. Garcia-Exposito, J.L. Brodsky, and R.W. Sobol. UBE3B is a calmodulin-regulated, mitochondria-associated E3 ubiquitin ligase. J. Biol. Chem. (2017) 292: 2470-2484
Buck, T.M., A.S. Jordahl, M.E. Yates, G.M. Pres
Buck, T.M., A.S. Jordahl, M.E. Yates, G.M. Preston, E. Cook, T.R. Kleyman, and J.L. Brodsky. Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein. Biochem. J. (2017) 474: 357-376
Preston, G.M., and J.L. Brodsky. The evol
Preston, G.M., and J.L. Brodsky. The evolving role of ubiquitin modification in endoplasmic reticulum associated degradation. Biochem. J. (2017) 474: 445-469
Chung, W. J., J.L. Goeckeler-Fried, V. Havasi,
Chung, W. J., J.L. Goeckeler-Fried, V. Havasi, A. Chiang, S.M. Rowe, Z.E. Plyler, J.S. Hong, M. Mazur, G.A. Piazza, A.B. Keeton, E.L. White, L. Rasmussen, A.M. Weissman, R.A. Denny, J.L Brodsky, and E.J. Sorscher. Increasing the Endoplasmic Reticulum Pool of the F508DEL Allele of the Cystic Fibrosis Transmembrane Conductance Regulator Leads to Greater Folding Correction by Small Molecule Therapeutics. PLoS ONE (2016) 11(10):e0163615
McClure, M.L., S. Barnes, J.L. Brodsky, and E.J
McClure, M.L., S. Barnes, J.L. Brodsky, and E.J. Sorscher. Trafficking and function of the cystic fibrosis transmembrane conductance regulator: A complex network of post-translational modifications. Am. J. Physiol. Lung Cell. Mol. Physiol. (2016) 311: L719-L733
Manos-Turvey, A., H.A. Al-Ashtal, C.B. Hartline
Manos-Turvey, A., H.A. Al-Ashtal, C.B. Hartline, M.N. Prichard, P. Wipf, and J.L. Brodsky. Dihydropyrimidinones and -thiones with improved activity against human polyomavirus family members. Bioorg. Med. Chem. Lettr. (2016) 26: 5087-5091
Sabnis*, A.J., C.J. Guerriero*, V. Olivas, A. S
Sabnis*, A.J., C.J. Guerriero*, V. Olivas, A. Sayana, J.H. Shue, J. Flanagan, S. Asthana, M. Loh, A.W. Paton, J.C. Paton, J. Gestwicki, P. Walter, J.S. Weissman, P. Wipf, J.L. Brodsky, T.G. Bivona. Combined chemical-genetic approach identifies cytosolic Hsp70 dependence in rhabdomyosarcoma. Proc. Natl. Acad. Sci. USA (2016) 113: 9015-9020
Veit G, Avramescu RG, Chiang AN, Houck SA, Cai
Veit G, Avramescu RG, Chiang AN, Houck SA, Cai Z, Peters KW, Hong JS, Pollard HB, Guggino WB, Balch WE, Skach WR, Cutting GR, Frizzell RA, Sheppard DN, Cyr DM, Sorscher EJ, Brodsky JL, Lukacs GL. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol Biol Cell. (2016) 27:424-33.
Prosser DC, Pannunzio AE, Brodsky JL, Thorner J
Prosser DC, Pannunzio AE, Brodsky JL, Thorner J, Wendland B, O'Donnell AF. α-Arrestins participate in cargo selection for both clathrin-independent and clathrin-mediated endocytosis. J Cell Sci. (2015) 128:4220-34
Brodsky, J.L. and R.A. Frizzell. A Combin
Brodsky, J.L. and R.A. Frizzell. A Combination Therapy for Cystic Fibrosis. Cell (2015) 163: 17
Chen, J., E.C. Ray, M.E. Yates, T.M. Buck, J.L.
Chen, J., E.C. Ray, M.E. Yates, T.M. Buck, J.L. Brodsky, C.L. Kinlough, K.L. Winarski, R.P. Hughey, T.R. Kleyman, and S. Sheng. Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle Domain. J. Biol. Chem. (2015) 290: 25140-25150
Marcoline, F.V., N. Bethel, C.J. Guerriero, J.L
Marcoline, F.V., N. Bethel, C.J. Guerriero, J.L. Brodsky, and M. Grabe. Membrane protein properties revealed through data-rich electrostatics calculations. Structure (2015) 23: 1526-1537
Manos-Turvey, A., J.L. Brodsky, and P. Wipf. Th
Manos-Turvey, A., J.L. Brodsky, and P. Wipf. The Effect of Structure and Mechanism of the Hsp70 Chaperone on the Ability to Identify Chemical Modulators and Therapeutics, In “Heat Shock Protein Inhibitors: Success Stories”, Springer, Top. Med. Chem. (2015) 81-129
Needham, P.G., H.J. Patel, G. Chiosis, P.H. Thi
Needham, P.G., H.J. Patel, G. Chiosis, P.H. Thibodeau, and J.L. Brodsky. Mutations in the yeast Hsp70, Ssa1, at P417 alter ATP cycling, interdomain coupling, and specific chaperone functions. J. Mol. Biol. (2015) 427: 2948-2965
An, P., J.L. Brodsky, and J.M. Pipas. The
An, P., J.L. Brodsky, and J.M. Pipas. The Conserved Core Enzymatic Activities and the Distinct Dynamics of Polyomavirus Large T Antigens. Arch. Biochem. Biophys. (2015) 573:23-31
Buck, T.M., R. Jordan, J. Lyons-Weiler, J.L. Ad
Buck, T.M., R. Jordan, J. Lyons-Weiler, J.L. Adelman, P.G. Needham, T.R. Kleyman, and J.L. Brodsky. The expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae. Physiol. Genomics (2015) 47: 198-214
Posimo, J.M., J.N. Weilnau, A.M. Gleixner, M.T.
Posimo, J.M., J.N. Weilnau, A.M. Gleixner, M.T. Broeren, N. Weiland, J.L. Brodsky, P. Wipf, and R.K. Leak. Heat shock protein defenses in the neo- and allocortex of the telencephalon. Neurobiol. Aging (2015) 36: 1924-1937
Crum, T.S., A.M. Gleixner, J.M. Posimo, D.M. Ma
Crum, T.S., A.M. Gleixner, J.M. Posimo, D.M. Mason, M.T. Broeren, S.D. Heinemann, P. Wipf, J.L. Brodsky, and R.K. Leak. Heat shock protein responses to aging and proteotoxicity in the olfactory bulb. J. Neurochem. (2015) 133: 780–794
Buck, T.M and J.L. Brodsky. Escaping the
Buck, T.M and J.L. Brodsky. Escaping the endoplasmic reticulum: Why does a molecular chaperone leave home for greener pastures? EMBO J. (2015) 34: 1-3
Zacchi, L.F., J.J. Caramelo, A.A. McCracken, an
Zacchi, L.F., J.J. Caramelo, A.A. McCracken, and J.L. Brodsky. Endoplasmic Reticulum Associated Degradation and Protein Quality Control. Encyclopedia of Cell Biology (R.A. Bradshaw and P. Stahl, Eds.), Elsevier (2016) 1: 596-611
Wipf, P., Eyer, B.R., Yamaguchi, Y., Zhang, F.,
Wipf, P., Eyer, B.R., Yamaguchi, Y., Zhang, F., Neal, M.D., Sodhi, C.P., Good, M., Branca, M., Prindle, T., Jr., Lu, P., Brodsky, J. L., and Hackam, D. J. Synthesis of anti-Inflammatory α- and β-Linked Acetamidopyranosides as Inhibitors of Toll-Like Receptor 4 (TLR4). Tetrahedron Lett. (2015) 56: 3097-3100
Li, H., H.C. Wu, Z. Liu, L.F. Zacchi, J.L. Brod
Li, H., H.C. Wu, Z. Liu, L.F. Zacchi, J.L. Brodsky, and M. Zolkiewski. Intracellular Complexes of the Early-Onset Torsion Dystonia-Associated AAA+ ATPase TorsinA. SpringerPlus (2014) 3:743
Howe, M.K., K. Bodoor, D.A. Carlson, P.F. Hughe
Howe, M.K., K. Bodoor, D.A. Carlson, P.F. Hughes, D.R. Loiselle, A.M. Jaeger, D.B. Darr, J.L. Jordan, L.M. Hunter, E.T. Molzberger, T.A. Gobillot, D.J. Thiele, J.L. Brodsky, N. Spector and T.A.J. Haystead. Identification of a Novel Allosteric Small Molecule Inhibitor of the Inducible Form of Heat Shock Protein 70. Chemistry & Biology (2014) 21: 1648–1659
Brodsky, J.L. and P.L. Clark. Protein Fol
Brodsky, J.L. and P.L. Clark. Protein Folding in the Cell, From Atom to Organism. FASEB J. (2014) 28: 5034-5038
Ireland, A.W., T.A. Gobillot, T. Gupta, S.P. Se
Ireland, A.W., T.A. Gobillot, T. Gupta, S.P. Seguin, M. Liang, L. Resnick, K. Lloyd, M.T. Goldberg, A. Manos-Turvey, J.M. Pipas, P. Wipf, and J.L. Brodsky. Synthesis and Structure Activity Relationships of Small Molecule Inhibitors of the Simian Virus 40 T Antigen Oncoprotein, an Anti-Polyomaviral Target. Bioorg. Med. Chem. (2014) 22: 6490-6502
Surlow, B.A., B. Cooley, P.G. Needham, J.L. Bro
Surlow, B.A., B. Cooley, P.G. Needham, J.L. Brodsky, and J. Patton-Vogt. Loss of Ypk1 accelerates Plb1-mediated phosphatidylcholine deacylation in S. cerevisiae. J. Biol. Chem. (2014) 289(45):31591-604
Alvaro, C.G., A.F. O’Donnell, D.C. Prosser, A.A
Alvaro, C.G., A.F. O’Donnell, D.C. Prosser, A.A. Augustine, A. Goldman, J.L. Brodsky, M.S. Cyert, B. Wendland, and J. Thorner. Specific a-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein coupled receptor Ste2. Mol. Cell. Biol. (2014) 34:2660-81.
Adam, C., A. Baeurle, J.L. Brodsky, P. Wipf, D.
Adam, C., A. Baeurle, J.L. Brodsky, P. Wipf, D. Schrama, J.C. Becker, and R. Houben. The HSP70 Modulator MAL3-101 inhibits Merkel Cell Carcinoma. PLoS ONE (2014) 9: e92041
Zacchi, L.F., H.C. Wu, S.L. Bell, L. Millen, A.
Zacchi, L.F., H.C. Wu, S.L. Bell, L. Millen, A.W. Paton, J.C. Paton, P.J. Thomas, M. Zolkiewski, and J.L. Brodsky. The BiP molecular chaperone plays multiple roles during the biogenesis of TorsinA, a AAA+ ATPase associated with the neurological disease Primary Torsion Dystonia. J. Biol. Chem. (2014) 289: 12727-12747
Nakatsukasa, K., T. Kamura, and J. L. Brodsky.&
Nakatsukasa, K., T. Kamura, and J. L. Brodsky. Recent technical developments in the study of ER-associated degradation. Curr. Opin. Cell Biol. (2014) 29:82–91
Brodsky, J.L., A. Merz, and T. Serio. Organelle
Brodsky, J.L., A. Merz, and T. Serio. Organelle and Proteome Quality Control Mechanisms: How Cells are able to Keep Calm and Carry On. Mol. Biol. Cell (2014) 25: 733-734
Hecht, K.A., A.F. O’Donnell, and J.L. Brodsky.
Hecht, K.A., A.F. O’Donnell, and J.L. Brodsky. The proteolytic landscape of the yeast vacuole. Cell. Logistics (2014) 4(1):e28023
Kang, Y., T. Taldone, H.J. Patel, P.D. Patel, A
Kang, Y., T. Taldone, H.J. Patel, P.D. Patel, A. Rodina, A. Gozman, R. Maharaj, C.C. Clement, M.R. Patel, J.L. Brodsky, J.C. Young, G. Chiosis. Heat shock protein 70 inhibitors. 1. 2,5'-thiodipyrimidine and 5-(phenylthio)pyrimidine acrylamides as irreversible binders to an allosteric site on heat shock protein 70. J. Med. Chem. (2014) 57:1188-1207.
Brodsky, J.L. The threads that tie protein-fold
Brodsky, J.L. The threads that tie protein-folding diseases. Dis. Model. Mech. (2014) 7: 3-4
Tran, J. R. and J. L. Brodsky. The Cdc48-
Tran, J. R. and J. L. Brodsky. The Cdc48-Vms1 complex maintains 26S proteasome architecture. Biochem. J. (2014) 458: 459-467
Kolb, A. R., P. G. Needham, C. Rothenberg, C. J
Kolb, A. R., P. G. Needham, C. Rothenberg, C. J. Guerriero, P. A. Welling, and J. L. Brodsky. ESCRT regulates surface expression of the Kir2.1 potassium channel. Mol. Biol. Cell (2014) 25: 276- 289
Butkinaree, C., L. Guo, B. Ramkhelawon, A. Wans
Butkinaree, C., L. Guo, B. Ramkhelawon, A. Wanschel, J.L. Brodsky, K.J. Moore, and E.A. Fisher. A Regulator of Secretory Vesicle Size, KLHL12, Facilitates the Secretion of Apolipoprotein B100 and Very Low Density Lipoproteins. Arterioscler. Thromb. Vasc. Biol. (2014) 34: 251-254
Simon, N., M. L. Bochman, S. Seguin, J. L. Brod
Simon, N., M. L. Bochman, S. Seguin, J. L. Brodsky, W. L. Seibel, and A. Schwacha. Ciprofloxacin is an inhibitor of the MCM2-7 replicative helicase. Biosci. Rep. (2013) 33(5), art:e00072
Brodsky, J.L. Just a trim, please: Refini
Brodsky, J.L. Just a trim, please: Refining ER degradation through deubiquitination. Cell (2013) 154: 479-481
Guerriero, C. J., K. F. Weiberth, and J. L. Bro
Guerriero, C. J., K. F. Weiberth, and J. L. Brodsky. Hsp70 Targets a Cytoplasmic Quality Control Substrate to the San1p Ubiquitin Ligase. J. Biol. Chem. (2013) 288: 18506-18520
Buck, T. M., L. Plavchak, A. Roy, B. F. Donnell
Buck, T. M., L. Plavchak, A. Roy, B. F. Donnelly, O. B. Kashlan, T. R. Kleyman, A. R. Subramanya, J. L. Brodsky. The Lhs1/GRP170 chaperones facilitate the endoplasmic reticulum associated degradation of the epithelial sodium channel. J. Biol. Chem. (2013) 288: 18366-18380
Neal, M.D., J. Hongpeng, B. Eyer, M. Good, C. J
Neal, M.D., J. Hongpeng, B. Eyer, M. Good, C. J. Guerriero, C. P. Sodhi, A. Afrazi, T. Prindle Jr, C. Ma, M. Branca, J. Ozoleck, T. R. Billiar, J. L. Brodsky, P. Wipf, and D. J. Hackam. Discovery and Validation of a New Class of Small Molecule TLR4 Inhibitors that Attenuate Endotoxemia and Necrotizing Enterocolitis. PLoS ONE (2013) 8 (6): e65779
Hecht, K.A., V. Wytiaz, T. Ast, M. Schuldiner,
Hecht, K.A., V. Wytiaz, T. Ast, M. Schuldiner, and J.L. Brodsky. Characterization of an M28 family member residing in the yeast vacuole. FEMS Yeast Res. (2013) 13: 471-484
Kilpatrick K, Novoa JA, Hancock T, Guerriero CJ
Kilpatrick K, Novoa JA, Hancock T, Guerriero CJ, Wipf P, Brodsky JL, Segatori L. Chemical induction of Hsp70 reduces α-synuclein aggregation in neuroglioma cells. ACS Chem Biol. (2013) 8: 1460-1468
Needham PG, Brodsky JL. How early studies on se
Needham PG, Brodsky JL. How early studies on secreted and membrane protein quality control gave rise to the ER associated degradation (ERAD) pathway: The early history of ERAD. Biochim Biophys Acta. (2013) 1883: 2447-2457
Nakatsukasa K, Brodsky JL, Kamura T. A stalled
Nakatsukasa K, Brodsky JL, Kamura T. A stalled retrotranslocation complex reveals physical linkage between substrate recognition and proteasomal degradation during ER associated degradation. Mol Biol Cell. (2013) 24: 1765-1775
Andreo U, Guo L, Chirieac DV, Tuyama AC, Monten
Andreo U, Guo L, Chirieac DV, Tuyama AC, Montenont E, Brodsky JL, Fisher EA. Insulin-Stimulated Degradation of Apolipoprotein B100: Roles of Class II Phosphatidylinositol-3-Kinase and Autophagy. PLoS One. 2013;8(3):e57590.
Abisambra J, Jinwal UK, Miyata Y, Rogers J, Bla
Abisambra J, Jinwal UK, Miyata Y, Rogers J, Blair L, Li X, Seguin SP, Wang L, Jin Y, Bacon J, Brady S, Cockman M, Guidi C, Zhang J, Koren J, Young ZT, Atkins CA, Zhang B, Lawson LY, Weeber EJ, Brodsky JL, Gestwicki JE, Dickey CA. Allosteric Heat Shock Protein 70 Inhibitors Rapidly Rescue Synaptic Plasticity Deficits by Reducing Aberrant Tau. Biol Psychiatry. (2013) 74: 367-374
Donnelly BF, Needham PG, Snyder AC, Roy A, Khad
Donnelly BF, Needham PG, Snyder AC, Roy A, Khadem S, Brodsky JL, Subramanya AR. Hsp70 and Hsp90 Multichaperone Complexes Sequentially Regulate Thiazide-Sensitive Cotransporter ER-Associated Degradation and Biogenesis. J Biol Chem. (2013) 288: 13124-13135
Miyata Y, Li X, Lee HF, Jinwal UK, Srinivasan S
Miyata Y, Li X, Lee HF, Jinwal UK, Srinivasan SR, Seguin SP, Young ZT, Brodsky JL, Dickey CA, Sun D, Gestwicki JE. Synthesis and Initial Evaluation of YM-08, a Blood-Brain Barrier Permeable Derivative of the Heat Shock Protein 70 (Hsp70) Inhibitor MKT-077, Which Reduces Tau Levels. ACS Chem Neurosci. (2013) 4: 930-939
Brodsky, J.L. Cleaning Up: ER-Associated Degrad
Brodsky, J.L. Cleaning Up: ER-Associated Degradation to the Rescue. Cell (2012) 151: 1163-1167
Gelling, C. L., I. W. Dawes, D. H. Perlmutter,
Gelling, C. L., I. W. Dawes, D. H. Perlmutter, E. A. Fisher, and J. L. Brodsky. The endosomal protein sorting receptor sortilin has a role in trafficking alpha-1 antitrypsin. Genetics (2012) 192: 889-903
Fisher, E. A. and J. L. Brodsky. The unfo
Fisher, E. A. and J. L. Brodsky. The unfolded protein response: A multifaceted regulator of lipid and lipoprotein metabolism. Cell Metab. (2012) 16: 407-408
Seguin, S. P., A. W. Ireland, T. Gupta, Y. Miya
Seguin, S. P., A. W. Ireland, T. Gupta, Y. Miyata, P. Wipf, J. M. Pipas, J. E. Gestwicki, and J. L. Brodsky. A screen for modulators of large T antigen’s ATPase activity uncovers novel inhibitors of simian virus 40 and BK virus replication. Antiviral Res. (2012) 96: 70-81
Tran, J., and J. L. Brodsky. Assays to me
Tran, J., and J. L. Brodsky. Assays to measure ER associated degradation (ERAD) in yeast, in “Ubiquitin family modifiers and the proteasome: Reviews and protocols” (Dohmen, J., and Scheffner, M., Eds.). Methods Mol. Biol. (2012) 832: 505-518
Hutt, D, M., D. M. Roth, M. Chalfant, R. T. You
Hutt, D, M., D. M. Roth, M. Chalfant, R. T. Youker, J. Matteson, J. L. Brodsky, and W. E. Balch. (2012) FKBP8 peptidyl-prolyl isomerase activity manages a late stage of CFTR folding and stability. J. Biol. Chem. (2012) 287: 21914-21925
Arora, R., M. Shuda, A. Gustafierro, H. Feng, T
Arora, R., M. Shuda, A. Gustafierro, H. Feng, T. Toptan, Y. Tolstov, D. Normolle, L. L. Vollmer, A. Vogt, A. Dömling, J. L. Brodsky, Y. Chang, and P. S. Moore. (2012) Viral knockdown reveals surviving as a therapeutic target for Merkel cell carcinoma. Science Transl. Med. (2012) 4(133):133ra56
Grubb, S., L. Guo, E. A. Fisher, and J. L. Brod
Grubb, S., L. Guo, E. A. Fisher, and J. L. Brodsky. (2012) Protein Disulfide Isomerases Contribute Differentially to the Endoplasmic Reticulum – Associated Degradation of Apolipoprotein B and Other Substrates. Mol. Biol. Cell (2012) 23(4):520-32
Guerriero, C., and J. L. Brodsky. (2012) On the
Guerriero, C., and J. L. Brodsky. (2012) On the precipice: the delicate balance between secreted protein folding and endoplasmic reticulum-associated degradation (ERAD) in human physiology. Physiol. Rev. (2012) 92: 537-576
Needham, P. G., K. Mikoluk, P. Dhakarwal, S. Kh
Needham, P. G., K. Mikoluk, P. Dhakarwal, S. Khadem, A. C. Snyder, A. R. Subramanya, and J. L. Brodsky. (2011) The Thiazide-Sensitive NaCl Cotransporter is Targeted for Chaperone-Dependent ER-Associated Degradation. J. Biol. Chem. 286:43611-21
Daghestani, H.N., G. Zhu, P.A. Johnston, S. Shi
Daghestani, H.N., G. Zhu, P.A. Johnston, S. Shinde, J.L. Brodsky, and B.W. Day. (2011) Characterization of inhibitors of glucocorticoid receptor nuclear translocation: A model of cytoplasmic dynein-mediated cargo transport. Assay Drug Devel. Technol. 10:46-60
Braunstein, M. J., S. S. Scott, C. M. Scott, S.
Braunstein, M. J., S. S. Scott, C. M. Scott, S. Behrman, P. Walter, P. Wipf, J. D. Coplan, W. J. Chirico, D. Joseph, J. L. Brodsky, and O. Batuman. (2011) Cytotoxic effects of the Hsp70 molecular chaperone inhibitor MAL3-101 on multiple myeloma. J. Oncol. 2011:232037
Seguin, S. P., C. W. Evans, M. Nebane, S. McKel
Seguin, S. P., C. W. Evans, M. Nebane, S. McKellip, S. Ananthan, N. A. Tower, M. Sosa, L. Rasmussen, E. L. White, B. E. Maki, D. S. Matharu, J. E. Golden, J. Aubé, J. L. Brodsky, and J. W. Noah. (2011) High-throughput Screening Identifies A Bisphenol Inhibitor of SV40 Large T-Antigen ATPase Activity. J. Biomol. Screen. 17:194-203
Falcone, D., M. P. Henderson, H. Nieuwland, C. M. Coughlan, J. L. Brodsky, and D. W. Andrews.&nbs
Falcone, D., M. P. Henderson, H. Nieuwland, C. M. Coughlan, J. L. Brodsky, and D. W. Andrews. (2011) Stability and function of the Sec61 translocation complex depends on the Sss1p tail-anchor sequence. Biochem. J. 436: 291-303
Brodsky, J. L., and W. R. Skach. (2011) Protein folding and quality control in the endoplasmic re
Brodsky, J. L., and W. R. Skach. (2011) Protein folding and quality control in the endoplasmic reticulum: recent lessons from yeast and mammalian systems. Curr. Opin. Cell Biol. 23: 464-475
Huryn, D.M., J.L. Brodsky, K.M. Brummond, P. G. Chambers, B. Eyre, A.W. Ireland, M. Kawasumi, M.G
Huryn, D.M., J.L. Brodsky, K.M. Brummond, P. G. Chambers, B. Eyre, A.W. Ireland, M. Kawasumi, M.G. LaPorte, K. Lloyd, B. Manteau, P. Nghiem, B. Quade, S.P. Seguin, and P. Wipf. (2011) Chemical Methodology as a Source of Small Molecule Checkpoint Inhibitors and Hsp70 Modulators. Proc. Natl. Acad. Sci. USA 108: 6757-6762
Bell, S. L., A. Chiang, and J. L. Brodsky. (2011). A malarial Hsp70 rescues chaperone-dependent a
Bell, S. L., A. Chiang, and J. L. Brodsky. (2011). A malarial Hsp70 rescues chaperone-dependent activities in ssa1 mutant yeast. PLoS One 6: e20047
Kolb, A. R., T. M. Buck, and J. L. Brodsky (2011) Saccharomyces cerevisiae as a model sy
Kolb, A. R., T. M. Buck, and J. L. Brodsky (2011) Saccharomyces cerevisiae as a model system for kidney disease: What can yeast tell us about renal function? Am. J. Physiol. 301: F1-F11
Yi, S.X., J.B. Benoit, M.A. Elnitsky, N. Kaufmann, J.L. Brodsky, M.L. Zeidel, D.L. Denlinger, and
Yi, S.X., J.B. Benoit, M.A. Elnitsky, N. Kaufmann, J.L. Brodsky, M.L. Zeidel, D.L. Denlinger, and J.r Lee RE (2011) Function and immuno-localization of aquaporins in the Antarctic midge Belgica antarctica. J Insect Physiol 57: 1096-1105
Tran, J.R., L.R. Tomsic, and J.L. Brodsky (2011) A Cdc48p-associated factor modulates endoplasmic
Tran, J.R., L.R. Tomsic, and J.L. Brodsky (2011) A Cdc48p-associated factor modulates endoplasmic reticulum-associated degradation, cell stress, and ubiquitinated protein homeostasis. J Biol Chem 286:5744-5755
Botha, M., A.N. Chiang, P.G. Needham, L.L. Stephens, H.C. Hoppe, S. Kulzer, J.M. Przyborski, K. L
Botha, M., A.N. Chiang, P.G. Needham, L.L. Stephens, H.C. Hoppe, S. Kulzer, J.M. Przyborski, K. Lingelbach, P. Wipf, J.L. Brodsky, A. Shonhai, and G.L. Blatch (2011) Plasmodium falciparum encodes a single cytosolic type I Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock. Cell Stress Chaperones 16: 389-401
Ahn, J.H., W. Luo, J. Kim, A. Rodina, C.C. Clement, J. Aguirre, W. Sun, Y. Kang, R. Maharaj, K. M
Ahn, J.H., W. Luo, J. Kim, A. Rodina, C.C. Clement, J. Aguirre, W. Sun, Y. Kang, R. Maharaj, K. Moulick, D. Zatorska, M. Kokoszka, J.L. Brodsky, and G. Chiosis (2011) Design of a Flexible Cell-Based Assay for the Evaluation of Heat Shock Protein 70 Expression Modulators. Assay Drug Dev Technol 9: 236-246
Gelling, C.L., and J.L. Brodsky (2010) Mechanisms underlying the cellular clearance of antitrypsi
Gelling, C.L., and J.L. Brodsky (2010) Mechanisms underlying the cellular clearance of antitrypsin Z: lessons from yeast expression systems. Proc Am Thorac Soc 7:363-367
Heo, J.M., N. Livnat-Levanon, E.B. Taylor, K.T. Jones, N. Dephoure, J. Ring, J. Xie, J.L. Brodsky
Heo, J.M., N. Livnat-Levanon, E.B. Taylor, K.T. Jones, N. Dephoure, J. Ring, J. Xie, J.L. Brodsky, F. Madeo, S.P. Gygi, K. Ashrafi, M.H. Glickman, and J. Rutter (2010) A stress-responsive system for mitochondrial protein degradation. Mol. Cell 40:465-480
Brodsky, J.L. (2010) The use of in vitro assays to measure endoplasmic reticulum-associated degra
Brodsky, J.L. (2010) The use of in vitro assays to measure endoplasmic reticulum-associated degradation. Methods Enzymol. 470:661-679
Brodsky, J.L. (2010) The special delivery of a tail-anchored protein: why it pays to use a dedica
Brodsky, J.L. (2010) The special delivery of a tail-anchored protein: why it pays to use a dedicated courier. Mol. Cell 40:5-7
Goeckeler, J.L., and J.L. Brodsky (2010) Molecular chaperones and substrate ubiquitination contro
Goeckeler, J.L., and J.L. Brodsky (2010) Molecular chaperones and substrate ubiquitination control the efficiency of endoplasmic reticulum-associated degradation. Diabetes Obes. Metab. 12 Sup:32-38
Wisen, S., E.B. Bertelsen, A.D. Thompson, S. Patury, P. Ung, L. Chang, C.G. Evans, G.M. Walter, P
Wisen, S., E.B. Bertelsen, A.D. Thompson, S. Patury, P. Ung, L. Chang, C.G. Evans, G.M. Walter, P. Wipf, H.A. Carlson, J.L. Brodsky, E.R. Zuiderweg, and J.E. Gestwicki (2010) Binding of a small molecule at a protein-protein interface regulates the chaperone activity of Hsp70-Hsp40. ACS Chem. Biol. 5:611-622
Vembar, S.S., M.C. Jonikas, L.M. Hendershot, J.S. Weissman, and J.L. Brodsky (2010) J domain co-c
Vembar, S.S., M.C. Jonikas, L.M. Hendershot, J.S. Weissman, and J.L. Brodsky (2010) J domain co-chaperone specificity defines the role of BiP during protein translocation. J. Biol. Chem. 285:22484-22494
Nakatsukasa, K., and J.L. Brodsky (2010) In vitro reconstitution of the selection, ubiqu
Nakatsukasa, K., and J.L. Brodsky (2010) In vitro reconstitution of the selection, ubiquitination, and membrane extraction of a polytopic ERAD substrate. Methods Mol. Biol. 619:365-376
Buck, T.M., A.R. Kolb, C.R. Boyd, T.R. Kleyman, and J.L. Brodsky (2010) The endoplasmic reticulum
Buck, T.M., A.R. Kolb, C.R. Boyd, T.R. Kleyman, and J.L. Brodsky (2010) The endoplasmic reticulum-associated degradation of the epithelial sodium channel requires a unique complement of molecular chaperones. Mol Biol Cell 21:1047-1058
Prof. Jeffrey Brodsky holds the Avinoff Chair in Biological Sciences at the University of Pittsburgh. He was born in Chicago, Illinois, and attended the University of Illinois where he received his bachelor's degree in Biochemistry, graduating magna cum laude with honors in 1985. He then entered the Biochemistry and Molecular Biology graduate program at Harvard University, receiving his PhD in 1990, and worked with Prof. Guido Guidotti on regulation of the sodium pump in the brain. Next, he moved to the University of California, Berkeley for post-doctoral research as an American Cancer Society Research Fellow and studied with Prof. Randy Schekman (Nobel Laureate, 2013), who pioneered the use of the yeast model to define how proteins are trafficked within the cell. Prof. Brodsky joined the Faculty in the Department of Biological Sciences at the University of Pittsburgh in 1994 and was promoted to Associate Professor in 2000. In 2006 he was promoted to Full Professor and was awarded the Avinoff Chair. Prof. Brodsky’s work now focuses on understanding how misfolded proteins are recognized and destroyed in the cell, and how defects in protein architecture can be corrected using drugs and genetic approaches. Based on his work, he received the University of Pittsburgh Chancellor's Outstanding Research Award in the Junior Division in 1998 and the Chancellor’s Outstanding Teaching Award in 2008, as well as the Pitt Innovator Award in 2007. In 2013, Dr. Brodsky was elected a Fellow of the American Association for the Advancement of Science (AAAS) and in 2022 he was again awarded the Chancellor's Outstanding Research Award (Senior Division), which was followed by elected membership in the American Academy of Arts and Sciences (2024). He also leads the Center for Protein Conformational Diseases on campus. Prof. Brodsky has served on the editorial boards of three journals, has published >250 scientific papers, holds 3 patents, and has acted as a scientific consultant for several disease foundations and biotech/pharmaceutical companies.