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William E. Balch, Ph.D.

Professor
Department of Molecular Medicine
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
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

Professional Experience

2013-2017 Professor, Cell and Molecular Biology (CMB), The Scripps Research Institute
1995-2012 Professor, Cell Biology, The Scripps Research Institute
-2012 Professor (Joint Appointment), Molecular Biology, The Scripps Research Institute

Selected References

All Publications

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

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. 2015 Nov 30. doi: 528(7583):510-6.

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