Proteins are the workhorses of the cell, and their function depends on their shape.
When proteins are misfolded or damaged, their shape becomes flawed and they can’t perform their duties. Faulty proteins need to be eliminated before they accumulate, clump or become toxic. Although there are intrinsic cell mechanisms that recognize defective proteins and attempt to remove them, these systems go awry as we age. Almost every age-related degenerative disease is linked to protein misfolding.
Our focus is on understanding how cells discriminate between functional and nonfunctional proteins. We have made important discoveries about the damaging impact of oxidative stress on protein structure and function in the neurodegenerative diseases of Alzheimer’s and Parkinson’s, metabolic diseases of diabetes and liver failure, and inflammatory disease and cancer. Our findings will be translated into new therapies that improve protein folding and preserve cell function in diseases that are major worldwide health concerns.
– Randal J. Kaufman, Ph.D., Program Director
Oubaha M, Miloudi K, Dejda A, Guber V, Mawambo G, Germain MA, Bourdel G, Popovic N, Rezende FA, Kaufman RJ, Mallette FA, Sapieha P
Sci Transl Med 2016 Oct 26 ;8(362):362ra144
SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein.
Huang TY, Zhao Y, Li X, Wang X, Tseng IC, Thompson R, Tu S, Willnow TE, Zhang YW, Xu H
J Neurosci 2016 Jul 27 ;36(30):7996-8011
Wang C, Niu M, Zhou Z, Zheng X, Zhang L, Tian Y, Yu X, Bu G, Xu H, Ma Q, Zhang YW
Neurobiol Aging 2016 Oct ;46:22-31
Role of Proinsulin Self-Association in Mutant <i>INS</i> Gene-Induced Diabetes of Youth.
Sun J, Xiong Y, Li X, Haataja L, Chen W, Mir SA, Lv L, Madley R, Larkin D, Anjum A, Dhayalan B, Rege N, Wickramasinghe NP, Weiss MA, Itkin-Ansari P, Kaufman RJ, Ostrov DA, Arvan P, Liu M
Diabetes 2020 May ;69(5):954-964
The ER Unfolded Protein Response Effector, ATF6, Reduces Cardiac Fibrosis and Decreases Activation of Cardiac Fibroblasts.
Stauffer WT, Blackwood EA, Azizi K, Kaufman RJ, Glembotski CC
Int J Mol Sci 2020 Feb 18 ;21(4)
Lebeaupin C, Blanc M, Vallée D, Keller H, Bailly-Maitre B
FEBS J 2020 May ;287(9):1722-1736
Development of a Reporter System Monitoring Regulated Intramembrane Proteolysis of the Transmembrane bZIP Transcription Factor ATF6α.
Kim JI, Kaufman RJ, Back SH, Moon JY
Mol Cells 2019 Nov 30 ;42(11):783-793
The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.
Pathak SS, Liu D, Li T, de Zavalia N, Zhu L, Li J, Karthikeyan R, Alain T, Liu AC, Storch KF, Kaufman RJ, Jin VX, Amir S, Sonenberg N, Cao R
Neuron 2019 Nov 20 ;104(4):724-735.e6
Publisher Correction: Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.
Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C
Nat Cell Biol 2019 Jul ;21(7):913