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Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology
Professor of Immunology, Department of Chemical Physiology
Institute for Childhood and Neglected Diseases
Department of Molecular Biology
Faculty, Kellogg School of Science and Technology

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

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. 2011 Apr 20. [Epub ahead of print]

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

Balch, W.E., D.M. Roth, and D.M. Hutt. 2011. Emergent properties of proteostasis in managing cystic fibrosis. Cold Spring Harb Perspect Biol. 3

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

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

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

Hutt, D.M., D. Herman, A.P. Rodrigues, S. Noel, J.M. Pilewski, J. Matteson, B. Hoch, W. Kellner, J.W. Kelly, A. Schmidt, P.J. Thomas, Y. Matsumura, W.R. Skach, M. Gentzsch, J.R. Riordan, E.J. Sorscher, T. Okiyoneda, J.R. Yates, 3rd, G.L. Lukacs, R.A. Frizzell, G. Manning, J.M. Gottesfeld, and W.E. Balch. 2010. Reduced histone deacetylase 7 activity restores function to misfolded CFTR in cystic fibrosis. Nat. Chem. Biol. 6:25-33.

Koulov, A.V., P. LaPointe, B. Lu, A. Razvi, J. Coppinger, M.Q. Dong, J. Matteson, R. Laister, C. Arrowsmith, J.R. Yates, 3rd, and W.E. Balch. 2010. Biological and Structural Basis for Aha1 Regulation of Hsp90 ATPase Activity in Maintaining Proteostasis in the Human Disease Cystic Fibrosis. Mol. Biol. Cell. 21:871-84.

Routledge, K.E., V. Gupta, and W.E. Balch. 2010. Emergent properties of proteostasis-COPII coupled systems in human health and disease. Mol. Membr. Biol. 27:385-97

Hutt, D., and W.E. Balch. 2010. Cell Biology. The proteome in balance. Science. 329:766-7.

Murray, A.N., J.P. Solomon, W.E. Balch, and J.W. Kelly. 2010. Discovery and characterization of a mammalian amyloid disaggregation activity. Protein Sci. 19:836-46.

Powers, E.T., R.I. Morimoto, A. Dillin, J.W. Kelly, and W.E. Balch. 2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78:959-91.

Bouchecareilh, M., J.J. Conkright, and W.E. Balch. 2010. Proteostasis Strategies for Restoring {alpha}1-Antitrypsin Deficiency. Proc Am Thorac Soc. 7:415-22

Page, L.J., J.Y. Suk, L. Bazhenova, S.M. Fleming, M. Wood, Y. Jiang, L.T. Guo, A.P. Mizisin, R. Kisilevsky, G.D. Shelton, W.E. Balch, and J.W. Kelly. 2009. Secretion of amyloidogenic gelsolin progressively compromises protein homeostasis leading to the intracellular aggregation of proteins. Proc. Natl. Acad. Sci. U. S. A. 106:11125-30.

Yonemoto, I.T., M.R. Wood, W.E. Balch, and J.W. Kelly. 2009. A general strategy for the bacterial expression of amyloidogenic peptides using BCL-XL-1/2 fusions. Protein Sci. 18:1978-86.

Solomon, J.P., I.T. Yonemoto, A.N. Murray, J.L. Price, E.T. Powers, W.E. Balch, and J.W. Kelly. 2009. The 8 and 5 kDa Fragments of Plasma Gelsolin Form Amyloid Fibrils by a Nucleated Polymerization Mechanism, while the 68 kDa Fragment Is Not Amyloidogenic. Biochemistry (Mosc). 48:11370-80.

Powers, E.T., R.I. Morimoto, A. Dillin, J.W. Kelly, and W.E. Balch. 2009. Biological and chemical approaches to diseases of proteostasis deficiency. Annu. Rev. Biochem. 78:959-91.

Page, L.J., J.Y. Suk, L. Bazhenova, S.M. Fleming, M. Wood, Y. Jiang, L.T. Guo, A.P. Mizisin, R. Kisilevsky, G.D. Shelton, W.E. Balch, and J.W. Kelly. 2009. Secretion of amyloidogenic gelsolin progressively compromises protein homeostasis leading to the intracellular aggregation of proteins. Proc. Natl. Acad. Sci. U. S. A. 106:11125-30.

Hutt, D.M., E.T. Powers, and W.E. Balch. 2009. The proteostasis boundary in misfolding diseases of membrane traffic. FEBS Lett. 583:2639-46.

An, Y., C.Y. Chen, B. Moyer, P. Rotkiewicz, M.A. Elsliger, A. Godzik, I.A. Wilson, and W.E. Balch. 2009. Structural and functional analysis of the globular head domain of p115 provides insight into membrane tethering. J. Mol. Biol. 391:26-41.

Links

The Balch Lab

Balch Selected Publications