Linda M. Hendershot, PhD
Linda M. Hendershot, PhD

Linda M. Hendershot, PhD

Member, St. Jude Faculty



PhD – University of Alabama, Birmingham

Research Interests

  • Control of the synthesis and assembly of secretory proteins in the ER    
  • Regulation of immunoglobulin transport
  • Elucidation of ER stress-induced signal transduction pathways
  • Role of the ER stress response in regulating tumor chemosensitivity

ER chaperones

Endoplasmic reticulum

Identification and disposal of misfolded secretory pathway proteins

Protein folding in the secretory pathway and the response of cells to alterations in the ER environment during normal and pathological conditions

The cellular response to imbalances in protein folding in the ER and its role in normal cellular differentiation and disease

Hendershot Lab

Selected Publications

Bai B, Pagala VR, High AA, Ichhaporia VP, Hendershot L, Peng J. Deep Profiling of Proteome and Phosphoproteome by Isobaric Labeling, Extensive Liquid Chromatography, and Mass Spectrometry. Methods of Enzymol 585:377-395, 2017.

Behnke J, Mann MJ, Scruggs F-L, Feige MJ, Hendershot LM. Members of the Hsp70 family recognize distinct types of sequences to execute ER quality control. Mol Cell 63:739-752, 2016. (preview in Mol Cell)

Joo JH, Wang B, Frankel E, Ge L, Xu L, Iyengar R, Li-Harms XJ, Wright C, Shaw TI, Lindsten T, Green DR, Peng J, Hendershot LM, Kilic F, Sze JY, Audhya A, Kundu M. Non-canonical role of ULK/ATG1 in ER-to-Golgi trafficking is essential for cellular homestasis. Mol Cell 62:491-506, 2016.

Preissler S, Chambers JE, Crespillo-Casado A, Avezov E, Miranda E, Perez J, Hendershot LM, Harding HP, Ron D. Physiological modulation of BiP activity by trans-protomer engagement of the interdomain linker. eLife 4:e08961, 2015.

Feige MJ, Behnke J, Mittag, T, Hendershot LM.  Dimerization-dependent folding underlies assembly control of the clonotypic αβ T cell receptor chains. J Biol Chem 290:26821-26831, 2015.

Ichhaporia V, Sanford T, Howes J, Marion TN, Hendershot LM.  Sil1, a nucleotide exchange factor for BiP, is not required for antibody assembly or secretion.  Mol Biol Cell 26:420-429, 2015.

Otero J, Lizak B, Hendershot LM.  Dissection of structural and functional requirements that underlie the interaction of ERdj3 with substrates. J Biol Chem 289:27504-27512, 2014.

Feige MJ, Gräwert MA, Marcinowski M, Hennig J, Hendershot LM, Buchner J. The structural analysis of shark IgNAR antibodies reveals evolutionary principles of immunoglobulins. Proc Natl Acad Sci USA 111:8155-8160, 2014.

Leitman J, Shenkman M, Gofman Y, Ben-Tal N, Hendershot LM, Lederkremer GZ. Herp recruits and compartmentalizes HRD1 and misfolded proteins for ERAD. Mol Biol Cell 25:1050-60, 2014.

Pereira ER, Frudd K, Awad W, Hendershot LM. ER stress and hypoxia response pathways interact to potentiate HIF-1 transcriptional activity on targets like VEGF. J Biol Chem 289(6):3352-3364, 2014. (Journal cover)

Behnke J, Hendershot LM. The large Hsp70 Grp170 binds to unfolded protein substrates in vivo with a regulation distinct from conventional Hsp70s. J Biol Chem 289:2899-2907, 2014.

Preston AM, Hendershot LM.  Identification of a second mechanism of translational control during the unfolded protein response that targets mTOR. J Cell Sci 126:4253-4261, 2013.

Feige MJ, Hendershot LM. Quality control of integral membrane proteins by assembly-dependent membrane integration. Mol Cell 51:297-309, 2013. (highlighted in Nature Reviews: Mol Cell Biol)

Shenkman M, Groisman B, Ron E, Avezov E, Hendershot LM, Lederkremer GZ. A shared ER-associated degradation pathway involving EDEM1 for glycosylated and nonglycosylated proteins. J Biol Chem 288:2167-2178, 2013.

Mann MJ, Liao N, Pereira ER, Hendershot LM. UPR-induced resistance to etoposide is downstream of PERK and independent of changes in topoisomerase II levels. PLoS ONE e47931, 2012.

Howes J, Shimizu Y, Feige MJ, Hendershot LM. C-terminal mutations destabilize Sil1/BAP and can cause Marinesco-Sjögren Syndrome. J Biol Chem 287:8552-8560, 2012.

Lai W*, Otero JH*, Hendershot LM, Snapp E. ERdj4 is a soluble endoplasmic reticulum DnaJ family protein that interacts with ERAD machinery. J Biol Chem 287:7969-7978, 2012.

Hendershot LM. Chaperone systems of the endoplasmic reticulum, in Houry, W.A. (ed.), Protein Homeostasis, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at, 2012.

Feige MJ, Hendershot LM. Disulfide bonds in ER protein folding and homeostasis. Curr Opin in Cell Biol 23:167-175, 2011.

Shimizu Y, Okuda-Shimizu Y, Hendershot LM. Ubiquitylation of an ERAD substrate occurs on multiple types of amino acids. Mol Cell 40:917-926, 2010 (Faculty of 1000, 3 evaluations).

Feige MJ, Hendershot LM, Buchner J. How antibodies fold. TIBS 35:189-198, 2010.

Otero J, Lizak, B, Hendershot LM. Life and death of a BiP substrate. Sem Cell & Dev Biol 21:472-478, 2010.

Vembar SS, Jonikas MC, Hendershot LM, Weissman JS, Brodsky JL. J domain co-chaperone specificity defines the role of BiP during protein translocation. J Biol Chem 285:22484-22494, 2010.

Pereira ER, Liao N, Neale GA, Hendershot LM. Transcriptional and Post-transcriptional Regulation of Proangiogenic Factors by the Unfolded Protein Response. PLoS One e12521, 2010.

Ma Y, Shimizu Y, Mann MJ, Jin Y, Hendershot LM. Plasma cell differentiation initiates a limited ER stress response by specifically suppressing the PERK-dependent branch of the UPR. Cell Stress & Chap 15:281-293, 2010.

Masciarelli S, Bertolotti M. Fagioli C, Fra A, Ron D, Hendershot LM, Sitia R. The CHOP transcription factor contributes to IgM polymerization and secretion in plasma cells. Mol Immunol 47:1356-1365, 2010.

Show More

Feige MJ, Hendershot LM, Buchner J. How antibodies fold. TIBS 35:189-198, 2010.

Feige MJ, Groscurth S, Marcinowski M, Shimizu Y, Kessler H, Hendershot LM, Buchner J. An unfolded CH1 domain controls the assembly and secretion of lgG antibodies. Mol Cell 34:569-579, 2009 (highlighted) (Faculty of 1000, 3 evaluations).

Shimizu Y, Meunier L, Hendershot LM. pERp1 is dramatically upregulated during plasma cell differentiation and contributes to the oxidative folding of immunoglobulin. PNAS 106:17013-17018, 2009.

Vembar S, Jin Y, Brodsky JL, Hendershot LM. The mammalian Hsp40 ERdj3 requires its Hsp70 interaction and substrate-binding properties to complement various yeast Hsp40-dependent functions. J Biol Chem 284:32462-32471, 2009.

Jin Y, Zhang M, Hendershot LM. ERdj3, a lumenal ER DnaJ homolog binds directly to unfolded proteins in the mammalian ER: identification of critical residues. Biochemistry 48:41-49, 2009.

Okuda-Shimizu Y, Shen Y, Hendershot LM. Quality control in the endoplasmic reticulum. In: The Handbook of Cell Signaling. Edited by R. Bradshaw and E. Dennis, Elsevier, Inc., pp. 2471-2476, 2009.

Shimizu Y, Hendershot LM. Oxidative folding: cellular strategies for dealing with the resultant equimolar production of reactive oxygen species. Forum Review, Antioxidants & Redox Signaling11;2317-2331, 2009.

Awad W, Estrada I, Shen Y, Hendershot LM. Characterization of BiP mutants that are unable to interact with resident ER DnaJ family members provides insights into inter-domain interactions in BiP. Proc Natl Acad Sci USA 105:1164-1169, 2008.

Petrova K, Oyadomari S, Hendershot LM, Ron D. Regulated association of misfolded endoplasmic reticulum proteins with p58IPK/DNAJc3. EMBO J 27:2862-2872, 2008.

Jin Y, Awad W, Petrova K, Hendershot LM. Regulated release of ERdj3 from unfolded proteins by BiP. EMBO J 27:2873-2882, 2008.

Okuda-Shimizu Y, Hendershot LM. Characterization of an ERAD pathway for non-glycosylated BiP substrates, which requires Herp. Mol Cell 28:544-554, 2007.

Last update: June 2017