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Thomas Rutkowski, PhD

Associate Professor
Anatomy & Cell Biology

Office: 1-570 BSB
Office Phone: 319-335-7739

Lab: 1-500 BSB

Lab Website: https://medicine.uiowa.edu/acb/profile/thomas-rutkowski

Our lab seeks to understand how cells adapt to chronic protein misfolding stress in physiology and disease

There are many ways in which stress can be manifested to a cell, including pathogenic infection, chemical insult, genetic mutation, nutrient deprivation, and even 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, cell signaling, and apoptosis.

A central paradox of the UPR, and in fact all stress response pathways, is that it is marked by the simultaneous activation of both adaptive signaling cascades that help alleviate stress, and apoptotic (i.e., death-promoting) cascades. Yet clearly there are ways for cells to commit to one fate over the other. Unfortunately, very little is understood about how mild but chronic stress leads to long-term changes in cellular programming, or what eventually causes cells to succumb to stress. We are using molecular and cell biological tools to understand the basic mechanisms of adaptation at the cellular level, including how cells integrate information on the nature, strength, and persistence of diverse stressors into discrete outcomes, such as life or death. We are also studying how chronic ER stress contributes to fatty liver in the mouse, which relates the mechanisms of adaptation to a disease (fatty liver disease) of enormous impact on public health.

PubMed link

Department/Program Affiliations:
Anatomy and Cell Biology
Molecular Medicine