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 J. Kaufman, Ph.D., Program Director



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

Therapeutic opportunities for pancreatic β-cell ER stress in diabetes mellitus.

Yong J, Johnson JD, Arvan P, Han J, Kaufman RJ

Nat Rev Endocrinol 2021 Jun 23 ;

Defects in Protein Folding and/or Quality Control Cause Protein Aggregation in the Endoplasmic Reticulum.

Poothong J, Jang I, Kaufman RJ

Prog Mol Subcell Biol 2021 ;59:115-143

S1P2-Gα12 signaling inhibits astrocytic glutamate uptake and mitochondrial oxygen consumption.

Jonnalagadda D, Kihara Y, Rivera R, Chun J

eNeuro 2021 Apr 23 ;

Calcineurin Activity Is Increased in Charcot-Marie-Tooth 1B Demyelinating Neuropathy.

Sidoli M, Reed CB, Scapin C, Paez P, Cavener DR, Kaufman RJ, D'Antonio M, Feltri ML, Wrabetz L

J Neurosci 2021 May 19 ;41(20):4536-4548

Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.

Liu M, Huang Y, Xu X, Li X, Alam M, Arunagiri A, Haataja L, Ding L, Wang S, Itkin-Ansari P, Kaufman RJ, Tsai B, Qi L, Arvan P

J Clin Invest 2021 Jan 19 ;131(2)

eIF2α controls memory consolidation via excitatory and somatostatin neurons.

Sharma V, Sood R, Khlaifia A, Eslamizade MJ, Hung TY, Lou D, Asgarihafshejani A, Lalzar M, Kiniry SJ, Stokes MP, Cohen N, Nelson AJ, Abell K, Possemato AP, Gal-Ben-Ari S, Truong VT, Wang P, Yiannakas A, Saffarzadeh F, Cuello AC, Nader K, Kaufman RJ, Costa-Mattioli M, Baranov PV, Quintana A, Sanz E, Khoutorsky A, Lacaille JC, Rosenblum K, Sonenberg N

Nature 2020 Oct ;586(7829):412-416

Show All Publications