Degenerative Diseases Program

Differentiation of Neural Stem Cells

Faulty proteins

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.

Director's statement

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 Kaufman, Ph.D., Program Director

Appointments

Adjunct Appointments

Wanda Reynolds, Ph.D.

Publications

Senescence-associated secretory phenotype contributes to pathological angiogenesis in retinopathy.

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

VPS35 regulates cell surface recycling and signaling of dopamine receptor D1.

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

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 Aug 26 ;

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

Proinsulin misfolding is an early event in the progression to type 2 diabetes.

Arunagiri A, Haataja L, Pottekat A, Pamenan F, Kim S, Zeltser LM, Paton AW, Paton JC, Tsai B, Itkin-Ansari P, Kaufman RJ, Liu M, Arvan P

Elife 2019 Jun 11 ;8

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 Jun ;21(6):755-767

Targeting the unfolded protein response in head and neck and oral cavity cancers.

Cole DW, Svider PF, Shenouda KG, Lee PB, Yoo NG, McLeod TM, Mutchnick SA, Yoo GH, Kaufman RJ, Callaghan MU, Fribley AM

Exp Cell Res 2019 Sep 1 ;382(1):111386

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