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

Appointments

Program Director

Randal J. Kaufman, Ph.D.

Primary Appointments

Jerold Chun, M.D., Ph.D.
Shengjie Feng, Ph.D.
Timothy Huang, Ph.D
Xiao Tian, Ph.D.

Secondary Appointments

Charles Spruck, Ph.D.

Publications

Chop/Ddit3 depletion in β cells alleviates ER stress and corrects hepatic steatosis in mice.

Yong J, Parekh VS, Reilly SM, Nayak J, Chen Z, Lebeaupin C, Jang I, Zhang J, Prakash TP, Sun H, Murray S, Guo S, Ayala JE, Satin LS, Saltiel AR, Kaufman RJ

Sci Transl Med 2021 Jul 28 ;13(604)

Trem2 deletion enhances tau dispersion and pathology through microglia exosomes.

Zhu B, Liu Y, Hwang S, Archuleta K, Huang H, Campos A, Murad R, Piña-Crespo J, Xu H, Huang TY

Mol Neurodegener 2022 Sep 2 ;17(1):58

Somatic APP gene recombination in Alzheimer's disease and normal neurons.

Lee MH, Siddoway B, Kaeser GE, Segota I, Rivera R, Romanow WJ, Liu CS, Park C, Kennedy G, Long T, Chun J

Nature 2018 Nov ;563(7733):639-645

Author Correction: Apoptotic stress causes mtDNA release during senescence and drives the SASP.

Victorelli S, Salmonowicz H, Chapman J, Martini H, Vizioli MG, Riley JS, Cloix C, Hall-Younger E, Machado Espindola-Netto J, Jurk D, Lagnado AB, Sales Gomez L, Farr JN, Saul D, Reed R, Kelly G, Eppard M, Greaves LC, Dou Z, Pirius N, Szczepanowska K, Porritt RA, Huang H, Huang TY, Mann DA, Masuda CA, Khosla S, Dai H, Kaufmann SH, Zacharioudakis E, Gavathiotis E, LeBrasseur NK, Lei X, Sainz AG, Korolchuk VI, Adams PD, Shadel GS, Tait SWG, Passos JF

Nature 2024 Jan 2 ;

Impact of eIF2α phosphorylation on the translational landscape of mouse embryonic stem cells.

Amiri M, Kiniry SJ, Possemato AP, Mahmood N, Basiri T, Dufour CR, Tabatabaei N, Deng Q, Bellucci MA, Harwalkar K, Stokes MP, Giguère V, Kaufman RJ, Yamanaka Y, Baranov PV, Tahmasebi S, Sonenberg N

Cell Rep 2023 Dec 28 ;43(1):113615

mRNA translation in astrocytes controls hippocampal long-term synaptic plasticity and memory.

Sharma V, Oliveira MM, Sood R, Khlaifia A, Lou D, Hooshmandi M, Hung TY, Mahmood N, Reeves M, Ho-Tieng D, Cohen N, Cheng PC, Rahim MMA, Prager-Khoutorsky M, Kaufman RJ, Rosenblum K, Lacaille JC, Khoutorsky A, Klann E, Sonenberg N

Proc Natl Acad Sci U S A 2023 Dec 5 ;120(49):e2308671120

Microglial targeted therapy relieves cognitive impairment caused by Cntnap4 deficiency.

Zhang W, Chen H, Ding L, Huang J, Zhang M, Liu Y, Ma R, Zheng S, Gong J, Piña-Crespo JC, Zhang Y

Exploration (Beijing) 2023 Jun ;3(3):20220160

Apoptotic stress causes mtDNA release during senescence and drives the SASP.

Victorelli S, Salmonowicz H, Chapman J, Martini H, Vizioli MG, Riley JS, Cloix C, Hall-Younger E, Machado Espindola-Netto J, Jurk D, Lagnado AB, Sales Gomez L, Farr JN, Saul D, Reed R, Kelly G, Eppard M, Greaves LC, Dou Z, Pirius N, Szczepanowska K, Porritt RA, Huang H, Huang TY, Mann DA, Masuda CA, Khosla S, Dai H, Kaufmann SH, Zacharioudakis E, Gavathiotis E, LeBrasseur NK, Lei X, Sainz AG, Korolchuk VI, Adams PD, Shadel GS, Tait SWG, Passos JF

Nature 2023 Oct ;622(7983):627-636

SNX17 Mediates Dendritic Spine Maturation via p140Cap.

Cui Q, Liang S, Li H, Guo Y, Lv J, Wang X, Qin P, Xu H, Huang TY, Lu Y, Tian Q, Zhang T

Mol Neurobiol 2023 Sep 13 ;

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