Glembotski Lab   >>   Publications  

Selected Publications

MANF is a new kind of chaperone that protects the heart ATF6 protein in the aged mouse heart provides remarkable protection against heart disease
Figure 1 - (top) MANF is a new kind of chaperone that protects the heart from ischemic damage and reductive stress. (bottom) Mutating the cysteine residues in MANF disrupts the C-terminal structure and the chaperone function.
Arrieta et al. (2020)J Biol Chem. 295(22):7566-7583. doi: 10.1074/jbc.RA120.013345. Epub 2020 Apr 23. PMID: 32327487 		Figure 2 - Shown are the temporal sequence of steps involved in mediating the initial (steps 1–4) and sustained (steps 5–7) aspects of growth and the interdependent roles of mTORC1 (mammalian/mechanistic target of rapamycin complex 1) and ATF6.
Blackwood et al Circ Res. 124(1):79-93. doi: 10.1161/CIRCRESAHA.118.313854. PMID: 30582446 (Cover Figure)
ATF6 as a regulator of a novel antioxidant gene New drug candidate, code named 147
Figure 3 - New function for ATF6 as a regulator of a novel antioxidant gene program demonstrates the mechanism by which ATF6 protects from ischemia/reperfusion damage in the heart.
Jin JK, et al. (2017) Circ Res. 120(5):862-875. 		Figure 4 - New drug candidate, code named 147, selectively activates ATF6 and protects mice from ischemia/reperfusion damage in heart, brain and kidney.
Blackwood et al. (2019)Nat Commun. 10(1):187. doi: 10.1038/s41467-018-08129-2. PMID: 30643122

2020

Blackwood EA, Thuerauf DJ, Stastna M, Stephens H, Sand Z, Pentoney A, Azizi K, Jakobi T, Van Eyk JE, Katus HA, Glembotski CC, Doroudgar S. (2020) Proteomic analysis of the cardiac myocyte secretome reveals extracellular protective functions for the ER stress response. J Mol Cell Cardiol. 143:132-144. doi: 10.1016/j.yjmcc.2020.04.012. Online ahead of print. PMID: 32339566

Arrieta A, Blackwood EA, Stauffer WT, Santo Domingo M, Bilal AS, Thuerauf DJ, Pentoney AN, Aivati C, Sarakki AV, Doroudgar S, Glembotski CC. (2020) Mesencephalic astrocyte-derived neurotrophic factor is an ER-resident chaperone that protects against reductive stress in the heart. J Biol Chem. 295(22):7566-7583. doi: 10.1074/jbc.RA120.013345. Epub 2020 Apr 23. PMID: 32327487
Meet the first author   

Glembotski CC, Arrieta A, Blackwood EA, Stauffer WT. (2020) ATF6 as a Nodal Regulator of Proteostasis in the Heart. Front Physiol. 11:267. doi: 10.3389/fphys.2020.00267. eCollection 2020. PMID: 32322217 Review.

Palmer JE, Brietske BM, Bate TC, Blackwood EA, Garg M, Glembotski CC, Cooley CB. (2020) Reactive Oxygen Species (ROS)-Activatable Prodrug for Selective Activation of ATF6 after Ischemia/Reperfusion Injury. ACS Med Chem Lett. 11(3):292-297. doi: 10.1021/acsmedchemlett.9b00299. eCollection 2020 Mar 12. PMID: 32184959

Blackwood EA, Bilal AS, Stauffer WT, Arrieta A, Glembotski CC. (2020) Designing Novel Therapies to Mend Broken Hearts: ATF6 and Cardiac Proteostasis. Cells. 9(3):602. doi: 10.3390/cells9030602. PMID: 32138230 Review.

Stauffer WT, Blackwood EA, Azizi K, Kaufman RJ, Glembotski CC. (2020) The ER Unfolded Protein Response Effector, ATF6, Reduces Cardiac Fibrosis and Decreases Activation of Cardiac Fibroblasts. Int J Mol Sci. 21(4):1373. doi: 10.3390/ijms21041373. PMID: 32085622

Stauffer WT, Arrieta A, Blackwood EA, Glembotski CC. (2020) Sledgehammer to Scalpel: Broad Challenges to the Heart and Other Tissues Yield Specific Cellular Responses via Transcriptional Regulation of the ER-Stress Master Regulator ATF6α. Int J Mol Sci. 21(3):1134. doi: 10.3390/ijms21031134. PMID: 32046286 Review.

Arrieta A, Blackwood EA, Stauffer WT, Glembotski CC. (2020) Integrating ER and Mitochondrial Proteostasis in the Healthy and Diseased Heart. Front Cardiovasc Med. 6:193. doi: 10.3389/fcvm.2019.00193. eCollection 2019. PMID: 32010709 Review.

Lindberg I, Glembotski CC. (2020) Physiological signaling in the absence of amidated peptides. Proc Natl Acad Sci U S A. 116(40):19774-19776. doi: 10.1073/pnas.1914001116. Epub 2019 Sep 12. PMID: 31515450 No abstract available.

 

2019
Glembotski CC, Rosarda JD, Wiseman RL. (2019) Proteostasis and Beyond: ATF6 in Ischemic Disease. Trends Mol Med. 25(6):538-550. doi: 10.1016/j.molmed.2019.03.005. Epub 2019 May 8. PMID: 31078432 Review.

Glembotski CC, Arrieta A, Blackwood EA. (2019) Unfolding the Roles of Mitochondria as Therapeutic Targets for Heart Disease. J Am Coll Cardiol. 73(14):1807-1810. doi: 10.1016/j.jacc.2018.12.089. PMID: 30975298. No Abstract Available.

Blackwood EA, Azizi K, Thuerauf DJ, Paxman RJ, Plate L, Kelly JW, Wiseman RL, Glembotski CC. (2019) Pharmacologic ATF6 activation confers global protection in widespread disease models by reprograming cellular proteostasis. Nat Commun. 10(1):187. doi: 10.1038/s41467-018-08129-2. PMID: 30643122

Blackwood EA, Hofmann C, Santo Domingo M, Bilal AS, Sarakki A, Stauffer W, Arrieta A, Thuerauf DJ, Kolkhorst FW, Müller OJ, Jakobi T, Dieterich C, Katus HA, Doroudgar S, Glembotski CC. (2019) ATF6 Regulates Cardiac Hypertrophy by Transcriptional Induction of the mTORC1 Activator, Rheb. Circ Res. 124(1):79-93. doi: 10.1161/CIRCRESAHA.118.313854. PMID:30582446 (see cover figure and meet the author below)

Cover photo Meet the first author

 

2018
Arrieta A, Blackwood EA, Glembotski CC. (2018) ER Protein Quality Control and the Unfolded Protein Response in the Heart. Curr. Topics in Micro and Immunol., 414:193-213. doi: 10.1007/82_2017_54. PMID:29026925

Blackwood, EA, Hofmann, C, Domingo, MS, Bilal, AS, Sarakki, A, Stauffer, W, Arrieta, A, Thuerauf, DJ, Kolkhorst, FW, Müller, OJ, Jakobi, T, Dieterich, C, Katus, HA, Doroudgar, D, Glembotski CC (2018) ATF6 regulates cardiac hypertrophy by transcriptional induction of the mTORC1 activator, Rheb. Circ. Res., in press.

Blackwood, E.A., Azizi, K., Thuerauf, DJ, Paxman, RJ, Plate, L, Kelly, JW, Wiseman, RL, Glembotski, C.C. (2018) Pharmacologic ATF6 Activation Confers Global Protection in Widespread Disease Models by Reprogramming Cellular Proteostasis. Nat Commun., in press.

 

2017
Glembotski, CC (2017) Expanding the Paracrine Hypothesis of Stem Cell-Mediated Repair in the Heart: When the Unconventional Becomes Conventional. Circ Res. 120(5):772-774.

Gray CB, Suetomi T, Xiang S, Mishra S, Blackwood EA, Glembotski CC, Miyamoto S, Westenbrink BD, Brown JH (2017) CaMKIIδ subtypes differentially regulate infarct formation following ex vivo myocardial ischemia/reperfusion through NF-κΒ and TNF-α. J Mol Cell Cardiol. 103:48-55

Jin JK, Blackwood EA, Azizi K, Thuerauf DJ, Fahem AG, Hofmann C, Kaufman RJ, Doroudgar S, Glembotski CC (2017) ATF6 Decreases Myocardial Ischemia/Reperfusion Damage and Links ER Stress and Oxidative Stress Signaling Pathways in the Heart. Circ Res. 120(5):862-875.

Yu Z, Sheng H, Liu S, Zhao S, Glembotski CC, Warner DS, Paschen W, Yang W. (2017) Activation of the ATF6 branch of the unfolded protein response in neurons improves stroke outcome. J Cereb Blood Flow Metab. 37(3):1069-1079.

 

2016
Doroudgar S, Quijada P, Konstandin M, Ilves K, Broughton K, Khalafalla FG, Casillas A, Nguyen K, Gude N, Toko H, Ornelas L, Thuerauf DJ, Glembotski CC, Sussman MA, Völkers M. (2016) S100A4 protects the myocardium against ischemic stress. J Mol Cell Cardiol. 100:54-63.

Reynolds JO, Quick AP, Wang Q, Beavers DL, Philippen LE, Showell J, Barreto-Torres G, Thuerauf DJ, Doroudgar S, Glembotski CC, Wehrens XH. (2016) Junctophilin-2 gene therapy rescues heart failure by normalizing RyR2-mediated Ca2+ release. Int J Cardiol. 225:371-380.

 

2015
Glembotski CC. (2015) Breaking down the COP9 Signalsome in the heart: how inactivating a protein ubiquitin ligase increases protein ubiquitylation and protects the heart. Circ Res. 117(11):914-6

Doroudgar, S., Völkers, M., Thuerauf, D.J., Khan, M., Mohsin, S., Respress, J.L., Wang, W., Gude, N.A., Müller, O.J., Wehrens, X.H., Sussman, M.A. andGlembotski, C.C. (2015) Hrd1 and ER-associated degradation, ERAD, are critical elements of the adaptive ER stress response in cardiac myocytes. CIRCRESAHA.115.306993.

 

2014
Glembotski, C.C. (2014) Roles for ATF6 and the sarco/endoplasmic reticulum protein quality control system in the heart. J. Mol. Cell. Cardiol., 71:11-15. PMCID: PMC4157898

Völkers, M., Doroudgar, S., Konstandin, M.H., Quijada, P., Din, S., Ornelas, L., Thuerauf, D.J., Gude, N., Glembotski C.C. and Sussman, M.A. (2014). PRAS40 prevents development of diabetic cardiomyopathy and improves hepatic insulin sensitivity in obesity. EMBO Mol. Med., 2014 Jan 1;6(1):57-65. PMCID: PMC3936489

Glembotski, C.C. (2014) Finding the Missing Link Between the Unfolded Protein Response and O-GlcNAcylation in the heart. Circ. Res., 115(6):546-8. doi: 10.1161/CIRCRESAHA.114.304855. PMCID: PMC4153403

 

2013
Doroudgar. S. and Glembotski. C.C. (2013) ATF6 and thrombospondin 4: the dynamic duo of the adaptive ER stress response. Circ Res. 112(1):9-12. Glembotski, C.C. (2013) Classic Studies of Cultured Cardiac Myocyte Hypertrophy: Interview with a Transformer. Circ. Res., 113:1112-6.

[Review] Doroudgar, S., and Glembotski, C.C. (2013) New Concepts of Endoplasmic Reticulum Function in the Heart: Programmed to Conserve. J. Mol. Cell. Cardiol., 55:85-91.

Völkers, M., Toko, H., Doroudgar, S., Din, S., Quijada, P., Joyo, A.Y., Ornelas, L., Joyo, E., Thuerauf, D.J., Konstandin, M.H., Gude, N., Glembotski, C.C., and Sussman, M.A. (2013) Pathological hypertrophy amelioration by PRAS40-mediated inhibition of mTORC1. Proc. Natl. Acad. Sci., U.S.A., 110:12661-6.

Völkers, M., Konstandin, M.H., Doroudgar, S., Toko, H., Quijada, P., Din, S., Joyo, A., Ornelas, L., Samse, K., Thuerauf, D.J., Gude, N., Glembotski, C.C., and Sussman, M.A. (2013) mTORC2 protects the heart from ischemic damage, Circulation, 128:2132-44.

Toko, H., Konstandin, M.H., Doroudgar, S., Ormachea, L., Joyo, E., Joyo, A.Y., Din, S., Gude, N.A., Collins, B., Völkers, M., Thuerauf, D.J., Glembotski, C.C., Chen, C.H., Lu, K.P., Müller, O.J., Uchida, T., and Sussman, M.A. (2013) Regulation of cardiac hypertrophic signaling by prolyl isomerase pin1. Circ. Res., 112(9):1244-1252.

Doroudgar S, and Glembotski CC (2013) ATF6 and thrombospondin 4: the dynamic duo of the adaptive endoplasmic reticulum stress response. Circ Res. 112(1):9-12.

 

2012
Eletto, D., Maganty, A., Eletto, D., Dersh, D., Makarewich, C., Biswas, C., Doroudgar, S., Glembotski, C.C., and Argon, Y. (2012) Limitation of Individual Folding Resources in the ER Leads to Outcomes Distinct from the Unfolded Protein Response. J. Cell Sci., 125(Pt 20):4865-75.

[Review] Glembotski CC. (2012) Roles for the sarco-/endoplasmic reticulum in cardiac myocyte contraction, protein synthesis, and protein quality control. Physiology (Bethesda). 2012 Dec;27(6):343-50.

Belmont, P.J., Chen, W.J., Thuerauf, D.J. and Glembotski, C.C. (2012) Regulation of microRNA expression in the heart by the ATF6 branch of the ER stress response. J. Mol. Cell. Cardiol. 52(5):1176-82.

[Review] Doroudgar S, Glembotski CC (2012) New concepts of endoplasmic reticulum function in the heart: Programmed to conserve. J Mol Cell Cardiol. doi:pii: S0022-2828(12)00374-4.

Glembotski CC (2012) Clarifying the cardiac proteasome paradox: protein quality control. Circ Res. 111(5):509-12.

Vekich JA, Belmont PJ, Thuerauf DJ, and Glembotski CC. (2012) Protein disulfide isomerase-associated 6is an ATF6-inducible ER stress response protein that protects cardiac myocytes from ischemia/reperfusion-mediated cell death. J Mol Cell Cardiol. 53(2):259-67.

Glembotski CC, Thuerauf DJ, Huang C, Vekich JA, Gottlieb RA, and Doroudgar S. (2012) Mesencephalic astrocyte-derived neurotrophic factor protects the heart from ischemic damage and is selectively secreted upon sarco/endoplasmic reticulum calcium depletion.J Biol Chem. 2012 Jul 27;287(31):25893-904.

[Review] Doroudgar, S. and Glembotski, C.C. (2012) Communication in the Heart: Cardiokines as Mediators of a Molecular Social Network. Muscle: Fundamental Biology and Mechanisms of Disease. Ed. J.A. Hill and E.N. Olson, Academic Press., p. 127-139.

 

2011
[Review] Doroudgar, S. and Glembotski, C.C. (2011) The Cardiokine Story Unfolds: Ischemic Stress Induced Protein Secretion in the Heart. Trends Mol. Med., 17(4):207-214.

[Review] Glembotski, C.C. (2011) Functions of the Cardiomyokine, MANF in Cardioprotection, Hypertrophy and Heart Failure. J. of Mol. Cell Cardiol., 51(4):512-517.

 

2010
Belmont PJ, Chen WJ, San Pedro MN, Thuerauf DJ, Gellings Lowe N, Gude N, Hilton B, Wolkowicz R, Sussman MA, and Glembotski CC. (2010) Roles for endoplasmic reticulum-associated degradation and the novel endoplasmic reticulum stress response gene Derlin-3 in the ischemic heart. Circ Res. 106(2):307-16.

 

2009
Whittaker R, Glassy MS, Gude N, Sussman MA, Gottlieb RA, Glembotski CC (2009) Kinetics of the translocation and phosphorylation of alphaB-crystallin in mouse heart mitochondria during ex vivo ischemia. Am J Physiol Heart Circ Physiol. 296(5):H1633-42.

Doroudgar S, Thuerauf DJ, Marcinko MC, Belmont PJ, and Glembotski CC. (2009) Ischemia activates the ATF6 branch of the endoplasmic reticulum (ER) stress response. J Biol Chem, 284(43):29735-45.

Meex, S.J.R, Weissglas-Volkov, Daphna, van der Kallen,, Carla J.H., Thuerauf, D.J., van Greevenbroek, Marleen M.J., Schalkwijk, Casper G., Stehouwer, Coen D.A., Feskens, Edith J.M., Heldens, L., Ayoubi, Torik A., Hofker, Marten H., Wouters, Bradly G., Vlietinck, R., Sinsheimer, J.S., Taskinen, M-R., Kuusisto, J. Laakso, M., de Bruin, T.W.A., Pajukanta, P., and Glembotski, C.C. (2009) The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels. Arterioscler Thromb Vasc Biol., 29(9):1322-7.

 

2008
Tadimalla A, Belmont PJ, Thuerauf DJ, Glassy MS, Martindale JJ, Gude N, Sussman MA, and Glembotski CC. (2008) Mesencephalic astrocyte-derived neurotrophic factor is an ischemia-inducible secreted endoplasmic reticulum stress response protein in the heart. Circ Res. 103(11):1249-58.

[Review] Glembotski, C.C. (2008) The Role of the Unfolded Protein Response in the Heart. J. Mol. Cell Cardiol., 44(3): 453-459.

Belmont PJ, Tadimalla A, Chen WJ, Martindale JJ, Thuerauf DJ, Marcinko M, Gude N, Sussman MA, and Glembotski, C.C. (2008) Coordination of growth and ER stress signaling by regulator of calcineurin 1 (RCAN1),a novel ATF6-inducible gene. J. Biol. Chem., 283(20):14012-21.

Jin, JK, Whittaker, R, Glassy, MS, Barlow, SB, Gottlieb, RA, and Glembotski, C.C. (2008) Localization of phosphorylated alphaB-crystallin to heart mitochondria during ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 294(1):H337-44.

 

2007
[Review] Glembotski, C.C. (2007) Getting a G-RRP on Regulated Exocytosis in the Heart. J. of Cell Biol., 179(3):371-3 (invited review)

[Review] Glembotski, C.C. (2007) Endoplasmic Reticulum (ER) Stress in the Heart. Circ Res., 101(10):975-84. (invited review)

Thuerauf, D.J., Marcinko, M., Belmont, P.J. and Glembotski, C.C. (2007) Effects of the isoform-specific characteristics of ATF6 alpha and ATF6 beta on endoplasmic reticulum stress response gene expression and cell viability. J. Biol. Chem., 282:22865-78.

 

2006
Martindale, J.J., Fernandez, R., Thuerauf, D.J. Whittaker, R., Gude, Natalie, Sussman, Mark A. and Glembotski, C.C. (2006) Endoplasmic Reticulum Stress Gene Induction and Protection from Ischemia/reperfusion Injury in the Hearts of Transgenic Mice with a Tamoxifen-regulated form of ATF6. Circulation Research, 98: 1186-1193.

[A commentary on the paper above paper]
Benjamin, I.J. (2006) Viewing a Stressful Episode of ER. Is ATF6 the Triage Nurse? Circulation Research, 98: 1120-1122.

Thuerauf, D.J., Marcinko, M., Gude, Natalie, Rubio, Marta, Sussman, Mark A., and Glembotski, C.C. (2006) Activation of the Unfolded Protein Response in Infarcted Mouse Heart and Hypoxic Cultured Cardiac Myocytes. Circulation Research., 99(3):275-82.

Wall, J.A., Wei, J., Ly, M, Belmont, P., Martindale, J.M., Tran, D., Sun, J., Yu, W., Oeller, P., Briggs, S., Sayen, M.R., Gottlieb, R.A. and Glembotski, C.C. (2006) Alterations in Oxidative Phosphorylation Complex Proteins in the Hearts of Transgenic Mice that Overexpress the p38 MAP Kinase Activator, MKK6. American J. of Physiol., 291(5):H2462-72.

 

2005
Kato, T., Muraski, J., Chen, Y., Tsujita, Y., Wall, J., Glembotski, C.C., Schaefer, E., Beckerle, M., and Sussman, M.A. (2005) ANP Promotes Cardiomyocyte Survival by cGMP-dependent Nuclear Accumulation of Zyxin and Akt. J. Clin. Invest., 115: 2716-2730.

McMullen, M.E., Bryant, P.W., Glembotski, C.C., Vincent, P.A. and Pumiglia, K.M. (2005) Activation of p38 has opposing effects on the proliferation and migration of endothelial cells. J. Biol. Chem. 280:20995-21003.

Martindale, J.J., Wall, J.A., Longoria, D.M., Aryal, P., Rockman, H.A. Guo, Y., Bolli, R. and Glembotski, C.C. (2005) Expression of MKK6 in the Heart Improves Functional Recovery from Ischemia In vitro and Protects Against Infarction In vivo. J. Biol. Chem. 280:669-76.

 

Can't open the pdf file? Get the reader here