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Selected Publications

ATF6 as a regulator of a novel antioxidant gene ATF6 protein in the aged mouse heart provides remarkable protection against heart disease
Figure 1 - 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.
Blackwood et al. (2018) Nat Commun., in press.
Figure 2 - Gene therapy studies show that restoring boosting ATF6 protein in the aged mouse heart provides remarkable protection against heart disease.
Jin JK, et al. (2017) Circ Res. 120(5):862-875.

New drug candidate, code named 147 MANF is a new kind of chaperone that protects the heart
Figure 3 - New drug candidate, code named 147, selectively activates ATF6 and protects mice from ischemia/reperfusion damage in heart, brain and kidney.
Blackwood et al. (2018) Nat Commun., in press.

Figure 4 - (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 (2018) Circ. Res., pending.

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.


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.


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.


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.


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


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.


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.


[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.


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.


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.


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.


[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.


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.


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.


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