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Molecular Medicine

Faculty

William E. Balch, Ph.D.

Professor
Department of Molecular Medicine
California Campus
Laboratory Website
webalch@scripps.edu
(858) 784-2310

Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology
Professor of Immunology, Department of Chemical Physiology
Institute for Childhood and Neglected Diseases
Professor, Department of Cell and Molecular Biology
Faculty, Graduate Program

Research Focus

Molecular basis for membrane trafficking and protein folding disease

Our laboratory is interested in understanding the rules that direct protein traffic through secretory pathway of eukaryotic cells. We use structural, biochemical, morphological and molecular tools to study mechanisms of protein folding and protein-protein interactions that mediate membrane vesicle targeting and fusion. We are particularly interested in defining the key trafficking defects that lead to hereditary amyloid disease, childhood emphysema, and cystic fibrosis, all diseases related to the inability of specific proteins to be properly transported to their site of function in the cell.

Education

Ph.D., Microbiology, University of Illinois, Urbana, IL, 1979

Selected References

For a complete list of publications: http://www.scripps.edu/balch/publications.html  

Wang, C., Bouchecareilh, M., Balch, W.E. 2017. Measuring the Effect of Histone Deacetylase Inhibitors (HDACi) on the Secretion and Activity of Alpha-1 Antitrypsin. Methods Mol. Biol.  1639:185-193.

Misharin, A.V., Morales-Nebreda, L., Reyfman, P.A., Cuda, C.M., Walter, J.M., McQuattie-Pimentel, A.C., Chen, C.I., Anekalla, K.R., Joshi, N., Williams, K.J.N., Abdala-Valencia, H., Yacoub, T.J., Chi, M., Chiu, S., Gonzalez-Gonzalez, F.J., Gates, K., Lam, A.P., Nicholson, T.T., Homan, P.J., Soberanes, S., Dominguez, S., Morgan, V.K., Saber, R., Shaffer, A., Hinchcliff, M., Marshall, S.A., Bharat, A., Berdnikovs, S., Bhorade, S.M., Bartom, E.T., Morimoto, R.I., Balch, W.E., Sznajder, J.I., Chandel, N.S., Mutlu, G.M., Jain, M., Gottardi, C.J., Singer, B.D., Ridge, K.M., Bagheri, N., Shilatifard, A., Budinger, G.R.S., Perlman, H. 2017. Monocyte-derived alveolar macrophages drive lung fibrosis and persist in the lung over the life span. J. Exp. Med. J Exp Med. 2017 Aug 7;214(8):2387-2404. doi: 10.1084/jem.20162152. Epub 2017 Jul 10.

Budinger, G.S., Kohanski, R.A., Gan, W., Kobor, M.S., Amaral, L.A., Armanios, M., Kelsey, K.T., Pardo, A., Tuder, R., Macian, F., Chandel, N., Vaughan, D., Rojas, M., Mora, A.L., Kovacs, E., Duncan, S.R., Finkel, T., Choi, A., Eickelberg, O., Chen, D., Agusti, A., Selman, M., Balch, W.E., Busse, P., Lin, A., Morimoto, R., Sznajder, J.I., Thannickal, V.J. 2017. The Intersection Of Aging Biology and The Pathobiology of Lung Diseases: A Joint NHLBI/NIA Workshop. J. Gerontol. A. Biol. Sci. Med. Sci. doi: 10.1093/gerona/glx090. [Epub ahead of print].

Pipalia, N.H., Subramanian, K., Mao, S., Ralph, H., Hutt, D.M., Scott, S.M., Balch, W.E., Maxfield, F.R. 2017. Histone deacetylase inhibitors correct the cholesterol storage defect in most NPC1 mutant cells. J. Lipid Res.. doi: 10.1194/jlr.M072140. [Epub ahead of print].

Wang, C., Balch, W.E. 2016. Managing the adaptive proteostatic landscape: restoring resilience in Alpha-1 antitrypsin deficiency. In: Adam Wanner, M.a.R.A.S., MD, Ph.D editor. Respir. Med.: Humana Press - Springer International Publishing AG Switzerland; p. 53-83.

Veit, G., Avramescu, R.G., Chiang, A.N., Houck, S.A., Cai, Z., Peters, K.W., Hong, J.S., Pollard, H.B., Guggino, W.B., Balch, W.E., Skach, W.R., Cutting, G.R., Frizzell, R.A., Sheppard, D.N., Cyr, D.M., Sorscher, E.J., Brodsky, J.L., Lukacs, G.L. 2016. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol. Biol. Cell. 27(3):424-433.

Pankow, S., Bamberger, C., Calzolari, D., Martinez-Bartolome, S., Lavallee-Adam, M., Balch, W.E., Yates, J.R., 3rd. 2015. F508 CFTR interactome remodelling promotes rescue of cystic fibrosis. Nature.  528(7583):510-516.

Amaral, M.D., Balch, W.E. 2015. Hallmarks of therapeutic management of the cystic fibrosis functional landscape. J. Cyst Fibrosis.14(6):687-99.

Rauniyar, N., Subramanian, K., Lavallee-Adam, M., Martinez-Bartolome, S., Balch, W.E., Yates, J.R., 3rd. 2015. Quantitative Proteomics of Human Fibroblasts with I1061T Mutation in Niemann-Pick C1 (NPC1) Protein Provides Insights into the Disease Pathogenesis. Mol. Cell Proteomics. 14(7):1734-1749.

Singh, J.K., Balch, W.E. 2015. Proteostatic hotspots in amyloid fibrils protect us from neurodegeneration. Dev. Cell. 32(6):659-660.

Roth, D.M., Hutt, D.M., Tong, J., Bouchecareilh, M., Wang, N., Seeley, T., Dekkers, J.F., Beekman, J.M., Garza, D., Drew, L., Masliah, E., Morimoto, R.I., Balch, W.E. 2014. Modulation of the maladaptive stress response to manage diseases of protein folding. PLoS Biol. 12(11):e1001998.

Rauniyar, N., Gupta, V., Balch, W.E., Yates, J.R. 2014. Quantitative proteomic profiling reveals differentially regulated proteins in cystic fibrosis cells. J. Proteome Res. 13(11):4668-75.

Balch, W. E., Sznajder, J. I., Budinger, S., Finley, D., Laposky, A. D., Cuervo, A. M., Benjamin, I. J., Barreiro, E., Morimoto, R. I., Postow, L., Weissman, A. M., Gail, D., Banks-Schlegel, S., Croxton, T., and Gan, W. 2014. Malfolded protein structure and proteostasis in lung diseases. Am. J. Respir. Crit. Care Med. 189, 96-103

Hamvas, A., Deterding, R., Balch, W. E., Schwartz, D. A., Albertine, K. H., Whitsett, J. A., Cardoso, W. V., Kotton, D. N., Kourembanas, S., and Hagood, J. S. 2014. Diffuse lung disease in children: Summary of a scientific conference. Pediatr. Pulmonol. 49, 400-409

Pottekat, A., Becker, S., Spencer, K. R., Yates, J. R., 3rd, Manning, G., Itkin-Ansari, P., and Balch, W. E. 2013. Insulin biosynthetic interaction network component, TMEM24, facilitates insulin reserve pool release. Cell Rep 4, 921-930

Roth, D. M., and Balch, W. E. 2013. Q-bodies monitor the quinary state of the protein fold. Nat Cell Biol 15, 1137-1139

Powers, E.T., Balch, W.E. 2013. Diversity in the origins of proteostasis networks - a driver for protein function in evolution. Nat. Rev. Mo. Cell Biol. 14(4):237-248.

Calamini, B., Silva, M. C., Madoux, F., Hutt, D. M., Khanna, S., Chalfant, M. A., Allais, C., Ouizem, S., Saldanha, S. A., Ferguson, J., Mercer, B. A., Michael, C., Tait, B. D., Garza, D., Balch, W. E., Roush, W. R., Morimoto, R. I., and Hodder, P. 2013. ML346: A Novel Modulator of Proteostasis for Protein Conformational Diseases. Probe Reports from the NIH Molecular Libraries Program.

Bannykh, S. I., Balch, W. E., Kelly, J. W., Page, L. J., and Shelton, G. D. 2013. Formation of gelsolin amyloid fibrils in the rough endoplasmic reticulum of skeletal muscle in the gelsolin mouse model of inclusion body myositis: comparative analysis to human sporadic inclusion body myositis. Ultrastruct. Pathol. 37, 304-311

Hutt, D.M., Balch, W.E. 2013. Expanding Proteostasis by Membrane Trafficking Networks. Cold Spring Harb Perspect Biol. 10.1101/cshperspect.a013383. [Epub ahead of print].

Gupta, V., and Balch, W.E. 2013. Protein folding: Salty sea regulators of cystic fibrosis. Nat. Chem. Biol. 9:12-14.

Bouchecareilh, M., Hutt, D.M., Szajner, P., Flotte, T.R., and Balch, W.E. 2012. Histone Deacetylase inhibitor (HDACi) Suberoylanilide Hydroxamic Acid (SAHA) Mediated Correction of Alpha-1 Antitrypsin Deficiency. J. Biol. Chem. 287: 38265-38278.

Hulleman, J.D., Balch, W.E., and Kelly, J.W. 2012. Translational attenuation differentially alters the fate of disease-associated fibulin proteins. FASEB J. 261: 4548-60.

Coppinger, J.A., Hutt, D.M., Razvi, A., Koulov, A.V., Pankow, S., Yates, J.R., 3rd, and Balch, W.E. 2012. A chaperone trap contributes to the onset of cystic fibrosis. PLoS One 7:e37682.

Bouchecareilh, M., and Balch, W.E. 2012. Proteostasis, an Emerging Therapeutic Paradigm for Managing Inflammatory Airway Stress Disease. Curr. Mol. Med. 1:815-826.

Hutt, D.M., Roth, D.M., Chalfant, M.A., Youker, R.T., Matteson, J., Brodsky, J.L., and Balch, W.E. 2012. FK506 Binding Protein 8 Peptidylprolyl Isomerase Activity Manages a Late Stage of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Folding and Stability. J. Biol. Chem. 287:21914-21925.

Solomon, J.P., Page, L.J., Balch, W.E., and Kelly, J.W. 2012. Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention. Crit. Rev. Biochem. Mol. Biol. 4: 282-296.

Calamini, B., Silva, M.C., Madoux, F., Hutt, D.M., Khanna, S., Chalfant, M.A., Saldanha, S.A., Hodder, P., Tait, B.D., Garza, D., Balch, W.E., and Morimoto, R.I. 2012. Small-molecule proteostasis regulators for protein conformational diseases. Nat. Chem. Biol. 8:185-196.

Hulleman, J.D., Kaushal, S., Balch, W.E., and Kelly, J.W. 2011. Compromised mutant EFEMP1 secretion associated with macular dystrophy remedied by proteostasis network alteration. Mol. Biol. Cell 22:4765-4775.

Hutt, D.M., Olsen, C.A., Vickers, C.J., Herman, D., Chalfant, M., Montero, A., Leman, L.J., Burkle, R., Maryanoff, B.E., Balch, W.E., and Ghadiri, M.R. 2011. Potential Agents for Treating Cystic Fibrosis: Cyclic Tetrapeptides that Restore Trafficking and Activity of DeltaF508-CFTR. ACS Med. Chem. Lett. 2:703-707.

Peters, K.W., T. Okiyoneda, W.E. Balch, I. Braakman, J.L. Brodsky, W.B. Guggino, C.M. Penland, H.B. Pollard, E.J. Sorscher, W.R. Skach, P.J. Thomas, G.L. Lukacs, and R.A. Frizzell. 2011. CFTR Folding Consortium: Methods Available for Studies of CFTR Folding and Correction. Methods Mol. Biol. 742:335-53.

Balch, W.E., and J.R. Yates, 3rd. 2011. Application of mass spectrometry to study proteomics and interactomics in cystic fibrosis. Methods Mol. Biol. 742:227-47.

Powers, E.T., and W.E. Balch. 2011. Protein folding: Protection from the outside. Nature. 471:42-3.

Balch, W.E. 2011. Introduction to Section II: Omics in the Biology of Cystic Fibrosis. Methods Mol. Biol. 742:189-91.

Zhang, X., C. Dong, Q.J. Wu, W.E. Balch, and G. Wu. 2011. Di-acidic motifs in the membrane-distal C-termini modulate the transport of angiotensin II receptors from the endoplasmic reticulum to the cell surface. J. Biol. Chem. 23:20525-35.

Roth, D.M., and W.E. Balch. 2011. Modeling general proteostasis: proteome balance in health and disease. Curr. Opin. Cell Biol. 2:126-34.

Balch, W.E., D.M. Roth, and D.M. Hutt. 2011. Emergent properties of proteostasis in managing cystic fibrosis. Cold Spring Harb Perspect Biol. 2:pii: a004499.

Bouchecareilh, M., and W.E. Balch. 2011. Proteostasis: a new therapeutic paradigm for pulmonary disease. Proc. Am. Thorac. Soc. 8:189-95.

Links

The Balch Lab

Balch Selected Publications

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty