About the Hendershot Lab

Protein production occurs in the endoplasmic reticulum. Here, proteins undergo origami-like folding into 3-dimensional structures that are critical to their function. Proteins that fail to fold properly must be degraded. More than 100 diseases are attributed to failures in protein folding or disposal. Our laboratory investigates mechanisms of protein folding and the impact of genetic mutations in disease development.

Science Team

Our research summary

One third of the human genome includes proteins that will enter the endoplasmic reticulum (ER) co-translationally where they will fold and assemble into native complexes before being transported to the cell surface or secreted.  All aspects of multicellular life are dependent on the fidelity of their maturation.  As such stringent quality control mechanisms are in place to ensure that improperly folded or assembled proteins are prevented from leaving the ER and traveling along the secretory pathway.  

Hendershot Lab

Our laboratory studies the molecular chaperones and folding enzymes that execute this critical checkpoint and the mechanisms to identify proteins that fail to reach their native conformation and target them for retrotranslocation to the cytosol for degradation by the proteasome.  If the capacity of these systems is exceeded, unfolded proteins accumulate in the ER and activate a signal transduction cascade known as the unfolded protein response (UPR). This response aims to restore ER homeostasis or, if unsuccessful, induce apoptosis. The UPR contributes to processes as diverse as differentiation, viral infections, neurodegeneration, and cancer. Our research aims to uncover the molecular aspects of protein folding in the ER and the consequences of failures in this critical process.   

We discovered the nucleotide exchange factor for one chaperone, and discovered that mutations in this protein cause Marinesco Sjörgen’s syndrome, an orphan disease that disrupts the function of multiple tissues leading to a host of problems for affected children. Every cell depends on these chaperones and their proper functioning. We have conducted a large study using experimental models to investigate the chaperones involved in Marinesco Sjörgen’s syndrome and identified the mechanisms leading to the progressive myopathy, one of the hallmarks associated with the disease. 

Hendershot Lab

Another major project in our laboratory centers on protein folding and how molecular chaperones engage proteins and protect them or target them for degradation. We are studying a specific protein involved in a genetic form of interstitial lung disease, which can manifest soon after birth and cause severe respiratory disfunction for affected children. We are also interested in how ER chaperones identify these abnormal proteins and make the determination to either facilitate folding or target them for destruction.  

The accumulation of proteins in the ER is involved in several diseases. Our laboratory identified many of the mechanisms underlying this accumulation and contributed to the understanding of how unfolded protein signals can drive transcriptional responses. Our research uses a variety of technologies and methodologies, including computational biology, proteomics, genome engineering, electron microscopy, and bioinformatics to address these areas. 

Selected Publications

About Linda M. Hendershot

Dr. Hendershot earned a BS from Eastern Kentucky University and a PhD in microbiology from the University of Alabama at Birmingham before beginning her longstanding research career with St. Jude. Since 1987, she has led a robust laboratory-based research program that explores protein folding in the cells and the biological impact of protein misfolding, including how the accumulation of unfolded proteins may contribute to disease.

Linda M. Hendershot, PhD

The team

Talented group of molecular and cell biologists passionate about using basic research to realize St. Jude’s mission to end catastrophic childhood diseases

Contact us

Linda M. Hendershot, PhD

Tumor Cell Biology
MS350
St. Jude Children Research Hospital

262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
901-595-2475 Linda.Hendershot@stjude.org
262 Danny Thomas Place
Memphis, TN, 38105-3678 USA
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