William Balch, PhD
Professor
Department of Molecular and Cellular Biology
Research Focus
Modeling the evolution of genetic variation in the human population to describe the role of spatial covariance in managing the function of the protein fold in health and disease in the individual.
The Balch laboratory works to link the evolution of genetic variation in the human population to experimental and computational approaches to describe and manage the function of the protein fold in health and disease.
Defining the role of genetic variation in shaping biological diversity is critical to understanding the global forces at play in health, disease, and aging. We generate an integrated view of genetic variation in the genome and the corresponding changes in the proteome in response to the environment and natural selection using novel machine learning tools that allow us to rigorously assess protein fold function and structure on a residue-by-residue basis at atomic resolution.
Current efforts utilize cell biological, molecular, biochemical and structural approaches in the context of state-of-the-art machine learning Gaussian Process (GP) and in silico computational platforms to link the sequence information found in the genome to the proteome managed by the proteostasis machinery (Hsp70 and Hsp90 co-chaperone systems). Our approach provides a standard model to begin to describe the evolution of protein fold design for any gene dictating health that is compromised in disease – and for development of novel therapeutic approaches to correct the folding problem in the individual.
Select Publications
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Sun, Shuhong; Wang, Chao; Hu, Junyan; Zhao, Pei; Wang, Xi; Balch, William Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.. Cell Rep Med. 2025.
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Zhao, Pei; Wang, Chao; Sun, Shuhong; Wang, Xi; Balch, William Tracing genetic diversity captures the molecular basis of misfolding disease.. Nat Commun. 2024, 15.
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Loguercio, Salvatore; Calverley, Ben C.; Wang, Chao; Shak, Daniel; Zhao, Pei; Sun, Shuhong; Budinger, G.R. S.; Balch, William E. Understanding the host-pathogen evolutionary balance through Gaussian process modeling of SARS-CoV-2. Patterns 2023, 4.
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Balch, William E.; Kelly, Jeffery; Wiseman, R. L.; Labaudiniere, Richard; Jiang, Xin; Grandjean, Julia; Kline, Gabe M.; Zhao, Pei; Wang, Chao; Sun, Shuhong Capturing the conversion of the pathogenic alpha-1-antitrypsin fold by ATF6 enhanced proteostasis. Cell Chemical Biology 2023, 22-42.e5.
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Balch, William E.; Morimoto, R. I.; Dillin, A.; Kelly, Jeffery W. Adapting proteostasis for disease intervention. Science 2008, 319, 916-919.
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Balch, William E.; Anglès, Frédéric; Wang, Chao Triangulating variation in the population to define mechanisms for precision management of genetic disease. Structure 2022.
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Wang, C.; Scott, S. M.; Subramanian, K.; Loguercio, S.; Zhao, P.; Hutt, D. M.; Farhat, N. Y.; Porter, F. D.; Balch, William E. Quantitating the epigenetic transformation contributing to cholesterol homeostasis using Gaussian process. Nature Communications 2019, 10.
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