Thomas Rutkowski, PhD

Portrait
Associate Professor of Anatomy and Cell Biology

Contact Information

Office: 1-570 Bowen Science Building
Iowa City, IA 52242
319-335-7739

Lab: 1-500 Bowen Science Building
Iowa City, IA 52242
319-335-7735

Education

BS, Biotechnology, University of Delaware
PhD, Cell Biology, University of California San Francisco

Post Doctoral Fellow, Howard Hughes Medical Institute, University of Michigan Medical Center

Education/Training Program Affiliations

Department of Cell and Developmental Graduate Program, Interdisciplinary Graduate Program in Molecular and Cellular Biology, Medical Scientist Training Program

Center, Program and Institute Affiliations

Center for Gene Therapy of Cystic Fibrosis and other Genetic Diseases, Fraternal Order of Eagles Diabetes Research Center, Holden Comprehensive Cancer Center

Research Summary

Our laboratory seeks to understand a fundamental but very poorly understood question in biology: When a cell encounters stress (i.e., anything that perturbs normal cellular function), how does it decide whether to adapt to the stress or die? We use diverse experimental approaches to address this question, encompassing systems biology, molecular and cell biology, and vertebrate genetics and physiology. By tackling this question, we hope to better understand diseases of stress, including neurodegeneration, cancer, metabolic syndrome, and others, and even normal cellular development and function. There are many ways in which stress can be manifested to a cell, including pathogenic infection, chemical insult, genetic mutation, nutrient deprivation, and the course of normal cellular function. The endoplasmic reticulum (ER) is the site of synthesis and folding of secretory and cell-surface proteins. The cellular response to ER stress (also known as the Unfolded Protein Response, or UPR) serves as a model for understanding not only the mechanisms by which stress is sensed, but also the ways in which the consequences of alterations of homeostasis in one location (i.e., the ER) impact diverse areas of cell function, including gene expression, metabolism, cancer, cell signaling, and apoptosis.

Publications

DeZwaan-McCabe, D., Sheldon, R. D., Gorecki, M. C., Guo, D. F., Gansemer, E. R., Kaufman, R. J., Rahmouni, K., Gillum, M. P., Taylor, E. B., Teesch, L. M. & Rutkowski, D. T. (2017). ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis. Cell reports, 19(9), 1794-1806. PMID: 28564599.

Gomez, J. A., Rutkowski, D. T. (2016). Experimental reconstitution of chronic ER stress in the liver reveals feedback suppression of BiP mRNA expression. eLife, 5, e20390. PMID: 27938665.

Jo, F., Jo, H., Hilzendeger, A. M., Thompson, A. P., Cassell, M. D., Rutkowski, D. T., Davisson, R. L., Grobe, J. L. & Sigmund, C. D. (2015). Brain endoplasmic reticulum stress mechanistically distinguishes the saline-intake and hypertensive response to deoxycorticosterone acetate-salt. Hypertension (Dallas, Tex. : 1979), 65(6), 1341-8. PMID: 25895586.

Mao, H. Z., Ehrhardt, N., Bedoya, C., Gomez, J. A., DeZwaan-McCabe, D., Mungrue, I. N., Kaufman, R. J., Rutkowski, D. T. & Péterfy, M. (2014). Lipase maturation factor 1 (lmf1) is induced by endoplasmic reticulum stress through activating transcription factor 6a (Atf6a) signaling. The Journal of biological chemistry, 289(35), 24417-27. PMID: 25035425.

Staber, J. M., Pollpeter, M. J., Arensdorf, A., Sinn, P. L., Rutkowski, D. T. & McCray, Jr, P. B. (2014). piggyBac-mediated phenotypic correction of factor VIII deficiency. Molecular therapy. Methods & clinical development, 1, 14042. PMID: 26015980.

Gomez, J. A., Tyra, H. M., DeZwaan-McCabe, D., Olivier, A. K. & Rutkowski, D. T. (2014). Synthetic embryonic lethality upon deletion of the ER cochaperone p58(IPK) and the ER stress sensor ATF6a. Biochemical and biophysical research communications, 443(1), 115-9. PMID: 24275136.

Hassan, I., Gaines, K. S., Hottel, W. J., Wishy, R. M., Miller, S. E., Powers, L. S., Rutkowski, D. T. & Monick, M. M. (2014). Inositol-requiring enzyme 1 inhibits respiratory syncytial virus replication. The Journal of biological chemistry, 289(11), 7537-46. PMID: 24497642.

Sadighi Akha, A. A., Theriot, C. M., Erb-Downward, J. R., McDermott, A. J., Falkowski, N. R., Tyra, H. M., Rutkowski, D. T., Young, V. B. & Huffnagle, G. B. (2013). Acute infection of mice with Clostridium difficile leads to eIF2a phosphorylation and pro-survival signalling as part of the mucosal inflammatory response. Immunology, 140(1), 111-22. PMID: 23668260.

Arensdorf, A. M., Rutkowski, D. T. (2013). Endoplasmic reticulum stress impairs IL-4/IL-13 signaling through C/EBPß-mediated transcriptional suppression. Journal of cell science, 126(Pt 17), 4026-36. PMID: 23813955.

Arensdorf, A. M., Diedrichs, D. & Rutkowski, D. T. (2013). Regulation of the transcriptome by ER stress: non-canonical mechanisms and physiological consequences. Frontiers in genetics, 4, 256. PMID: 24348511.

DeZwaan-McCabe, D., Riordan, J. D., Arensdorf, A. M., Icardi, M. S., Dupuy, A. J. & Rutkowski, D. T. (2013). The stress-regulated transcription factor CHOP promotes hepatic inflammatory gene expression, fibrosis, and oncogenesis. PLoS Genetics, 9(12), e1003937. PMID: 24367269.

Chikka, M. R., McCabe, D. D., Tyra, H. M. & Rutkowski, D. T. (2013). C/EBP homologous protein (CHOP) contributes to suppression of metabolic genes during endoplasmic reticulum stress in the liver. The Journal of biological chemistry, 288(6), 4405-15. PMID: 23281479.

Arensdorf, A. M., Dezwaan McCabe, D., Kaufman, R. J. & Rutkowski, D. T. (2013). Temporal clustering of gene expression links the metabolic transcription factor HNF4a to the ER stress-dependent gene regulatory network. Frontiers in genetics, 4, 188. PMID: 24069029.

Zagorodna, O., Martin, S. M., Rutkowski, D. T., Kuwana, T., Spitz, D. R. & Knudson, C. M. (2012). 2-deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines. Oncogene, 31(22), 2738-49. PMID: 21986940.

Tyra, H. M., Spitz, D. R. & Rutkowski, D. T. (2012). Inhibition of fatty acid oxidation enhances oxidative protein folding and protects hepatocytes from endoplasmic reticulum stress. Molecular biology of the cell, 23(5), 811-9. PMID: 22262455.

Hassan, I. H., Zhang, M. S., Powers, L. S., Shao, J. Q., Baltrusaitis, J., Rutkowski, D. T., Legge, K. & Monick, M. M. (2012). Influenza A viral replication is blocked by inhibition of the inositol-requiring enzyme 1 (IRE1) stress pathway. The Journal of biological chemistry, 287(7), 4679-89. PMID: 22194594.

Sadighi Akha, A. A., Harper, J. M., Salmon, A. B., Schroeder, B. A., Tyra, H. M., Rutkowski, D. T. & Miller, R. A. (2011). Heightened induction of proapoptotic signals in response to endoplasmic reticulum stress in primary fibroblasts from a mouse model of longevity. The Journal of biological chemistry, 286(35), 30344-51. PMID: 21757703.

Wu, J., Ruas, J. L., Estall, J. L., Rasbach, K. A., Choi, J. H., Ye, L., Boström, P., Tyra, H. M., Crawford, R. W., Campbell, K. P., Rutkowski, D. T., Kaufman, R. J. & Spiegelman, B. M. (2011). The unfolded protein response mediates adaptation to exercise in skeletal muscle through a PGC-1a/ATF6a complex. Cell metabolism, 13(2), 160-9. PMID: 21284983.

Rutkowski, D. T., Hegde, R. S. (2010). Regulation of basal cellular physiology by the homeostatic unfolded protein response. The Journal of cell biology, 189(5), 783-94. PMID: 20513765.

Rutkowski, D. T. (2009). A gluconeogenic tryst in the nucleus, with ER stress as the third wheel. Science signaling, 2(96), pe72. PMID: 19903938.

Wang, J., Farr, G. W., Zeiss, C. J., Rodriguez-Gil, D. J., Wilson, J. H., Furtak, K., Rutkowski, D. T., Kaufman, R. J., Ruse, C. I., Yates, 3rd, J. R., Perrin, S., Feany, M. B. & Horwich, A. L. (2009). Progressive aggregation despite chaperone associations of a mutant SOD1-YFP in transgenic mice that develop ALS. Proceedings of the National Academy of Sciences of the United States of America, 106(5), 1392-7. PMID: 19171884.

Rutkowski, D. T., Wu, J., Back, S. H., Callaghan, M. U., Ferris, S. P., Iqbal, J., Clark, R., Miao, H., Hassler, J. R., Fornek, J., Katze, M. G., Hussain, M. M., Song, B., Swathirajan, J., Wang, J., Yau, G. D. & Kaufman, R. J. (2008). UPR pathways combine to prevent hepatic steatosis caused by ER stress-mediated suppression of transcriptional master regulators. Developmental cell, 15(6), 829-40. PMID: 19081072.

Rutkowski, D. T., Kang, S. W., Goodman, A. G., Garrison, J. L., Taunton, J., Katze, M. G., Kaufman, R. J. & Hegde, R. S. (2007). The role of p58IPK in protecting the stressed endoplasmic reticulum. Molecular biology of the cell, 18(9), 3681-91. PMID: 17567950.

Rutkowski, D. T., Kaufman, R. J. (2007). That which does not kill me makes me stronger: adapting to chronic ER stress. Trends in biochemical sciences, 32(10), 469-76. PMID: 17920280.

Wu, J., Rutkowski, D. T., Dubois, M., Swathirajan, J., Saunders, T., Wang, J., Song, B., Yau, G. D. & Kaufman, R. J. (2007). ATF6alpha optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Developmental cell, 13(3), 351-64. PMID: 17765679.

Rutkowski, D. T., Arnold, S. M., Miller, C. N., Wu, J., Li, J., Gunnison, K. M., Mori, K., Sadighi Akha, A. A., Raden, D. & Kaufman, R. J. (2006). Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS biology, 4(11), e374. PMID: 17090218.

Zhang, K., Shen, X., Wu, J., Sakaki, K., Saunders, T., Rutkowski, D. T., Back, S. H. & Kaufman, R. J. (2006). Endoplasmic reticulum stress activates cleavage of CREBH to induce a systemic inflammatory response. Cell, 124(3), 587-99. PMID: 16469704.

Rutkowski, D. T., Kaufman, R. J. (2004). A trip to the ER: coping with stress. Trends in cell biology, 14(1), 20-8. PMID: 14729177.

Rutkowski, D. T., Kaufman, R. J. (2003). All roads lead to ATF4. Developmental cell, 4(4), 442-4. PMID: 12689582.

Rutkowski, D. T., Ott, C. M., Polansky, J. R. & Lingappa, V. R. (2003). Signal sequences initiate the pathway of maturation in the endoplasmic reticulum lumen. The Journal of biological chemistry, 278(32), 30365-72. PMID: 12771148.

Lingappa, V. R., Rutkowski, D. T., Hegde, R. S. & Andersen, O. S. (2002). Conformational control through translocational regulation: a new view of secretory and membrane protein folding. BioEssays : news and reviews in molecular, cellular and developmental biology, 24(8), 741-8. PMID: 12210535.

Rutkowski, D. T., Lingappa, V. R. & Hegde, R. S. (2001). Substrate-specific regulation of the ribosome- translocon junction by N-terminal signal sequences. Proceedings of the National Academy of Sciences of the United States of America, 98(14), 7823-8. PMID: 11416167.