A schematic model of the unfolded protein response. Source: W Stroberg et al. (2018) Molecular Biology of the Cell 29, 2969-3062.

Molecular Control Mechanisms of the Unfolded Protein Response

A schematic model of the unfolded protein response. Source: W Stroberg et al. (2018) Molecular Biology of the Cell 29, 2969-3062.

Molecular Control Mechanisms of the Unfolded Protein Response

Roughly one third of all proteins produced in humans are folded in the endoplasmic reticulum (ER). Cellular protein homeostasis requires continuous monitoring of stress in the ER. Stress-detection networks control protein homeostasis by mitigating the deleterious effects of protein accumulation, such as aggregation and misfolding, with precise modulation of chaperone production. The unfolded protein response (UPR) is a multifaceted cellular response to excess unfolded or misfolded proteins within the ER. UPR activation is triggered by heightened protein concentration within the ER lumen which leads to accelerated protein folding and degradation within the ER along with decreased protein synthesis. If efforts to regain protein homeostasis are unsuccessful, the cell begins the process of cell death (apoptosis). Malfunction of the UPR has been implicated in numerous protein misfolding diseases. During aging, the function of the UPR is compromised causing a decline in the ability of the cell to handling protein folding and aggregation, and age-associated diseases.

Our long term goal is deciphering the control mechanism of the UPR to open new therapeutic avenues for the treatment of a range of age-associated and protein folding diseases.

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Santiago Schnell
John A. Jacquez Collegiate Professor of Physiology

My research focuses on developing standard-methods to obtain high quality measurements in the biomedical sciences and mathematical models of biomedical systems.