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

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

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

ER stress and inflammation crosstalk in obesity.

Ajoolabady A, Lebeaupin C, Wu NN, Kaufman RJ, Ren J

Med Res Rev 2022 Aug 17 ;

Endoplasmic reticulum stress in liver diseases.

Ajoolabady A, Kaplowitz N, Lebeaupin C, Kroemer G, Kaufman RJ, Malhi H, Ren J

Hepatology 2022 May 6 ;

S1P/S1PR3 signalling axis protects against obesity-induced metabolic dysfunction.

Chakrabarty S, Bui Q, Badeanlou L, Hester K, Chun J, Ruf W, Ciaraldi TP, Samad F

Adipocyte 2022 Dec ;11(1):69-83

In Vitro Stimulation of IRE1α/XBP1-Deficient B Cells with LPS.

Zhu H, Jiang C, Kaufman RJ, Li H, Singh N

Methods Mol Biol 2022 ;2378:221-231

ATF6 is required for efficient rhodopsin clearance and retinal homeostasis in the P23H rho retinitis pigmentosa mouse model.

Lee EJ, Chan P, Chea L, Kim K, Kaufman RJ, Lin JH

Sci Rep 2021 Aug 11 ;11(1):16356

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