Jeffrey L. Brodsky

  • Professor, Avinoff Chair of Biological Sciences
  • Protein quality control

Contact

Office: (412) 624-4831
Lab: (412) 624-4831
A320 Langley Hall
4249 Fifth Avenue
Pittsburgh, PA 15260

Figure 1.  A specific protein in yeast can be visualized using fluorescence microscopy

All secreted proteins, and most that ultimately reside within the cell, must traverse the secretory pathway, a network of intracellular organelles housing the “machines” that help secreted proteins mature.Critical components of these machines are a class of proteins known as molecular chaperones, some of which are associated with the endoplasmic reticulum (ER). If, however, protein folding is inefficient or slow, a secreted protein may be targeted for destruction by a process we termed ER Associated Degradation, or ERAD. During ERAD, proteins are selected as being defective, are modified with ubiquitin, and are degraded by the proteasome, a multi-catalytic protease that resides in the cytoplasm. Molecular chaperones are required for ERAD by “deciding” whether a protein is sufficiently mature to transit through the secretory pathway. Molecular chaperones can also direct ERAD substrates to the proteasome. The importance ofunderstanding the molecular mechanism of ERAD and molecular chaperone action is underscored by the fact that several human diseases—including cystic fibrosis, heart and liver disease, diabetes, and neurodegenerative diseases—can arise from defects in chaperone-mediated folding of secreted proteins and/or the ERAD pathway.

Figure 2.  A transcriptional profile analysis of yeast expressing CFTR, the protein that when mutated gives rise to cystic fibrosis

For our studies, the Brodsky laboratory primarily utilizes a model eukaryotic organism, the yeast Saccharomyces cerevisiae (Figure 1). Yeast possess the same intracellular membrane organization and molecular chaperones as human cells but are amenable to rapid genetic analysis. Moreover, the basic machinery required for ERAD is completely conserved between yeast and humans. Current research in the Brodsky laboratory is directed toward understanding how molecular chaperones in the ER and the cytoplasm facilitate ERAD and protein folding in the cell. Human proteins expressed heterologously in yeast, such as CFTR (Figure 2), are being examined as substrates for ERAD and chaperone-mediated folding. Data derived from our genetic studies are complemented by biochemical assays that recapitulate specific steps in the ERAD pathway, and by studies using cells from higher organisms in which disease phenotypes are more relevant. In parallel, we have identified and characterized small molecule modulators of specific molecular chaperones, some of which have potent inhibitory effects on cancer cells and on the replication of human viruses.

Dr. Brodsky is also the Director of the Center for Protein Conformational Diseases (please see www.proteindiseasecenter.pitt.edu/about-our-center for additional information).

Students may find the Metabolic Pathways and Regulation (BIOSC1820) Course Website useful.

E-mail Lab

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), In press

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., In press

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
Dr. Brodsky received his Ph.D. in 1990 with Guido Guidotti at Harvard University, performed his postdoctoral studies with Randy Schekman at the University of California, Berkeley, and joined the Department in 1994.