Chad Grueter, PhD

Portrait
Associate Professor of Internal Medicine - Cardiovascular Medicine

Contact Information

Primary Office
4332 Pappajohn Biomedical Discovery Building
Iowa City, IA 52242
319-335-3379

Education

PhD, Molecular Physiology and Biophysics, Vanderbilt University
Postdoctoral Fellow, UT Southwestern Medical Center

Center, Program and Institute Affiliations

Fraternal Order of Eagles Diabetes Research Center

Research Summary

The basis for the research in my laboratory lies in my strong interest in understanding the transcriptional and posttranscriptional processes that are disrupted in heart disease. In our previous studies, we identified a novel transcriptional signaling pathway in the heart that mediates the heart’s ability to regulate whole body metabolism. Through a combination of pharmacological and genetic gain- and loss-of-function studies in mice, we found the heart is capable of regulating whole body metabolism through a mechanism that is governed by MED13 and miR-208a. MED13 is a particularly interesting component of the Mediator complex because it functions as a molecular bridge between the core complex and kinase submodule, providing a mechanism for spatial and temporal control of Mediator-dependent regulation of transcription. Recently, we have identified a key role for other components of the Mediator complex including CDK8 and MED1 in regulation cardiac function and the cardiac transcriptional profile. We primarily utilize mutant mouse models to study the proteomic, molecular, bioinformatic and biochemical methods to study the molecular signaling events controlling cardiac transcriptional response to stress.

Publications

Chen, X., Zhabyeyev, P., Azad, A. K., Wang, W., Minerath, R. A., DesAulniers, J., Grueter, C. E., Murray, A. G., Kassiri, Z., Vanhaesebroeck, B. & Oudit, G. Y. (2019). Endothelial and cardiomyocyte PI3Kß divergently regulate cardiac remodelling in response to ischaemic injury. Cardiovascular research, 115(8), 1343-1356. PMID: 30496354.

Minerath, R. A., Hall, D. D. & Grueter, C. E. (2019). Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure. Heart failure reviews. PMID: 30972522.

Minerath, R. A., Dewey, C. M., Hall, D. D. & Grueter, C. E. (2019). Regulation of cardiac transcription by thyroid hormone and Med13. Journal of molecular and cellular cardiology, 129, 27-38. PMID: 30769017.

Hall, D. D., Spitler, K. M. & Grueter, C. E. (2019). Disruption of cardiac Med1 inhibits RNA polymerase II promoter occupancy and promotes chromatin remodeling. American journal of physiology. Heart and circulatory physiology, 316(2), H314-H325. PMID: 30461303.

Guo, A., Wang, Y., Chen, B., Wang, Y., Yuan, J., Zhang, L., Hall, D., Wu, J., Shi, Y., Zhu, Q., Chen, C., Thiel, W. H., Zhan, X., Weiss, R. M., Zhan, F., Musselman, C. A., Pufall, M., Zhu, W., Au, K. F., Hong, J., Anderson, M. E., Grueter, C. E. & Song, L. S. (2018). E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator. Science (New York, N.Y.), 362(6421). PMID: 30409805.

Hall, D. D., Ponce, J. M., Chen, B., Spitler, K. M., Alexia, A., Oudit, G. Y., Song, L. S. & Grueter, C. E. (2017). Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure. JCI insight, 2(15). PMID: 28768905.

Spitler, K. M., Ponce, J. M., Oudit, G. Y., Hall, D. D. & Grueter, C. E. (2017). Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming. American journal of physiology. Heart and circulatory physiology, 312(4), H768-H780. PMID: 28159809.

Dewey, C. M., Spitler, K. M., Ponce, J. M., Hall, D. D. & Grueter, C. E. (2016). Cardiac-Secreted Factors as Peripheral Metabolic Regulators and Potential Disease Biomarkers. Journal of the American Heart Association, 5(6). PMID: 27247337.

Guo, A., Hall, D., Zhang, C., Peng, T., Miller, J. D., Kutschke, W., Grueter, C. E., Johnson, F. L., Lin, R. Z. & Song, L. S. (2015). Molecular Determinants of Calpain-dependent Cleavage of Junctophilin-2 Protein in Cardiomyocytes. The Journal of biological chemistry, 290(29), 17946-55. PMID: 26063807.

Baskin, K. K., Grueter, C. E., Kusminski, C. M., Holland, W. L., Bookout, A. L., Satapati, S., Kong, Y. M., Burgess, S. C., Malloy, C. R., Scherer, P. E., Newgard, C. B., Bassel-Duby, R. & Olson, E. N. (2014). MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver. EMBO molecular medicine, 6(12), 1610-21. PMID: 25422356.

Long, C., Grueter, C. E., Song, K., Qin, S., Qi, X., Kong, Y. M., Shelton, J. M., Richardson, J. A., Zhang, C. L., Bassel-Duby, R. & Olson, E. N. (2014). Ataxia and Purkinje cell degeneration in mice lacking the CAMTA1 transcription factor. Proceedings of the National Academy of Sciences of the United States of America, 111(31), 11521-6. PMID: 25049392.

Grueter, C. E. (2013). Mediator complex dependent regulation of cardiac development and disease. Genomics, proteomics & bioinformatics, 11(3), 151-7. PMID: 23727265.

Carrer, M., Liu, N., Grueter, C. E., Williams, A. H., Frisard, M. I., Hulver, M. W., Bassel-Duby, R. & Olson, E. N. (2012). Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378*. Proceedings of the National Academy of Sciences of the United States of America, 109(38), 15330-5. PMID: 22949648.

Grueter, C. E., van Rooij, E., Johnson, B. A., DeLeon, S. M., Sutherland, L. B., Qi, X., Gautron, L., Elmquist, J. K., Bassel-Duby, R. & Olson, E. N. (2012). A cardiac microRNA governs systemic energy homeostasis by regulation of MED13. Cell, 149(3), 671-83. PMID: 22541436.

Moresi, V., Carrer, M., Grueter, C. E., Rifki, O. F., Shelton, J. M., Richardson, J. A., Bassel-Duby, R. & Olson, E. N. (2012). Histone deacetylases 1 and 2 regulate autophagy flux and skeletal muscle homeostasis in mice. Proceedings of the National Academy of Sciences of the United States of America, 109(5), 1649-54. PMID: 22307625.

Backs, J., Stein, P., Backs, T., Duncan, F. E., Grueter, C. E., McAnally, J., Qi, X., Schultz, R. M. & Olson, E. N. (2010). The gamma isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption. Proceedings of the National Academy of Sciences of the United States of America, 107(1), 81-6. PMID: 19966304.

Backs, J., Backs, T., Neef, S., Kreusser, M. M., Lehmann, L. H., Patrick, D. M., Grueter, C. E., Qi, X., Richardson, J. A., Hill, J. A., Katus, H. A., Bassel-Duby, R., Maier, L. S. & Olson, E. N. (2009). The delta isoform of CaM kinase II is required for pathological cardiac hypertrophy and remodeling after pressure overload. Proceedings of the National Academy of Sciences of the United States of America, 106(7), 2342-7. PMID: 19179290.

Khoo, M. S., Grueter, C. E., Eren, M., Yang, J., Zhang, R., Bass, M. A., Lwin, S. T., Mendes, L. A., Vaughan, D. E., Colbran, R. J. & Anderson, M. E. (2008). Calmodulin kinase II inhibition disrupts cardiomyopathic effects of enhanced green fluorescent protein. Journal of molecular and cellular cardiology, 44(2), 405-10. PMID: 18048055.

Grueter, C. E., Abiria, S. A., Wu, Y., Anderson, M. E. & Colbran, R. J. (2008). Differential regulated interactions of calcium/calmodulin-dependent protein kinase II with isoforms of voltage-gated calcium channel beta subunits. Biochemistry, 47(6), 1760-7. PMID: 18205403.

Grueter, C. E., Colbran, R. J. & Anderson, M. E. (2007). CaMKII, an emerging molecular driver for calcium homeostasis, arrhythmias, and cardiac dysfunction. Journal of molecular medicine (Berlin, Germany), 85(1), 5-14. PMID: 17119905.

Khoo, M. S., Li, J., Singh, M. V., Yang, Y., Kannankeril, P., Wu, Y., Grueter, C. E., Guan, X., Oddis, C. V., Zhang, R., Mendes, L., Ni, G., Madu, E. C., Yang, J., Bass, M., Gomez, R. J., Wadzinski, B. E., Olson, E. N., Colbran, R. J. & Anderson, M. E. (2006). Death, cardiac dysfunction, and arrhythmias are increased by calmodulin kinase II in calcineurin cardiomyopathy. Circulation, 114(13), 1352-9. PMID: 16982937.

Grueter, C. E., Abiria, S. A., Dzhura, I., Wu, Y., Ham, A. J., Mohler, P. J., Anderson, M. E. & Colbran, R. J. (2006). L-type Ca2+ channel facilitation mediated by phosphorylation of the beta subunit by CaMKII. Molecular cell, 23(5), 641-50. PMID: 16949361.

Wu, Y., Shintani, A., Grueter, C., Zhang, R., Hou, Y., Yang, J., Kranias, E. G., Colbran, R. J. & Anderson, M. E. (2006). Suppression of dynamic Ca(2+) transient responses to pacing in ventricular myocytes from mice with genetic calmodulin kinase II inhibition. Journal of molecular and cellular cardiology, 40(2), 213-23. PMID: 16413575.

Zhang, R., Dzhura, I., Grueter, C. E., Thiel, W., Colbran, R. J. & Anderson, M. E. (2005). A dynamic alpha-beta inter-subunit agonist signaling complex is a novel feedback mechanism for regulating L-type Ca2+ channel opening. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 19(11), 1573-5. PMID: 15994413.

Zhang, R., Khoo, M. S., Wu, Y., Yang, Y., Grueter, C. E., Ni, G., Price, E. E., Thiel, W., Guatimosim, S., Song, L. S., Madu, E. C., Shah, A. N., Vishnivetskaya, T. A., Atkinson, J. B., Gurevich, V. V., Salama, G., Lederer, W. J., Colbran, R. J. & Anderson, M. E. (2005). Calmodulin kinase II inhibition protects against structural heart disease. Nature medicine, 11(4), 409-17. PMID: 15793582.