Scripps Research Joint Appointments

The Skaggs Institute for Chemical Biology
Professor of Immunology, Department of Chemical Physiology
Institute for Childhood and Neglected Diseases
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

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

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

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