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Javier Gomez

Mentor: Thomas Rutkowski, PhD

Year Entered Into Program: 2010

PhD Institution: University of Iowa, 2016

Affiliations

  • Molecular and Cellular Biology Program

Research Description

The general goal of my current research project is to understand how the endoplasmic reticulum (ER) senses and deals with stress from the cell through the unfolded protein response (UPR). The UPR mediated by three proteins within the ER: ATF6, Ire1 and Perk. These proteins sense stress, and act to alleviate it by inhibiting protein synthesis, degrading mRNA's or even cell death under extreme conditions. Although originally defined as sensing stress arising from misfolded proteins, protein aggregation and excess protein synthesis, it has been recently shown that the UPR has a much broader role in cellular homeostasis.

Previous studies from our lab have suggested that the UPR plays an important role in establishing cellular homeostasis through transcriptional programming. The UPR has been shown to modulate genes involved in lipid biosynthesis. These observations brought about the idea that the UPR regulates more processes in the cell than just those sensed when proteins are misfolded.

However, little is known about how the UPR senses these stresors and how it modulates its response to them. The UPR must be able to discern between different stresses, activate one or more of the UPR resident components and culminate in up- or downregulation of genes to return the cell to homeostasis. However, the UPR must also be able to identify the strength and persistence of a stress, in addition to the type. The UPR must balance competing processes, such as upregulation of ER chaperones versus downregulation of protein synthesis; or in the most extreme case, between adaptation and survival or apoptosis.

My research goal is to understand how the UPR senses different stresses and how it modulates it output towards those stresses. In this complex signaling pathway, there are many proteins and genes involved in modulating the response. The specific contribution of the UPR components is paramount in determining how the UPR functions.

Awards

  • Travel grant, Computational Cell Biology Summer Course, Cold Spring Harbor Laboratory, NY, 2011
  • University of Iowa Presidential Fellowship, 2010-2011

Publications

  1. Gomez, J.A., Rutkowski, D.T.: Experimental reconstitution of chronic ER stress in the liver reveals feedback suppression of BiP mRNA expression. Elife 5:e20390, 2016.  PMCID: PMC5179193