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
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)
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
Phosphorylation of eIF2α Promotes Schwann Cell Differentiation and Myelination in CMT1B Mice with Activated UPR.
Scapin C, Ferri C, Pettinato E, Bianchi F, Del Carro U, Feltri ML, Kaufman RJ, Wrabetz L, D'Antonio M
J Neurosci 2020 Oct 14 ;40(42):8174-8187
Soluble SORLA Enhances Neurite Outgrowth and Regeneration through Activation of the EGF Receptor/ERK Signaling Axis.
Stupack J, Xiong XP, Jiang LL, Zhang T, Zhou L, Campos A, Ranscht B, Mobley W, Pasquale EB, Xu H, Huang TY
J Neurosci 2020 Jul 29 ;40(31):5908-5921
Hetz C, Zhang K, Kaufman RJ
Nat Rev Mol Cell Biol 2020 Aug ;21(8):421-438
Unbiased Profiling of the Human Proinsulin Biosynthetic Interaction Network Reveals a Role for Peroxiredoxin 4 in Proinsulin Folding.
Tran DT, Pottekat A, Mir SA, Loguercio S, Jang I, Campos AR, Scully KM, Lahmy R, Liu M, Arvan P, Balch WE, Kaufman RJ, Itkin-Ansari P
Diabetes 2020 Aug ;69(8):1723-1734