MSTPublications: August 2024
ER-phagy drives age-onset remodeling of endoplasmic reticulum structure-function and lifespan.
Donahue E, Hepowit NL, Keuchel B, Mulligan AG, Johnson DJ, Ellisman M, Arrojo E Drigo R, MacGurn J, Burkewitz K.
bioRxiv [Preprint]. 2024 Aug 8:2024.08.07.607085. doi: 10.1101/2024.08.07.607085.
The endoplasmic reticulum (ER) comprises an array of structurally distinct subdomains, each with characteristic functions. While altered ER-associated processes are linked to age-onset pathogenesis, whether shifts in ER morphology underlie these functional changes is unclear. We report that ER remodeling is a conserved feature of the aging process in models ranging from yeast to C. elegans and mammals. Focusing on C. elegans as an exemplar of metazoan aging, we find that as animals age, ER mass declines in virtually all tissues and ER morphology shifts from rough sheets to tubular ER. The accompanying large-scale shifts in proteomic composition correspond to the ER turning from protein synthesis to lipid metabolism. To drive this substantial remodeling, ER-phagy is activated early in adulthood, promoting turnover of rough ER in response to rises in luminal protein-folding burden and reduced global protein synthesis. Surprisingly, ER remodeling is a pro-active and protective response during aging, as ER-phagy impairment limits lifespan in yeast and diverse lifespan-extending paradigms promote profound remodeling of ER morphology even in young animals. Altogether our results reveal ER-phagy and ER morphological dynamics as pronounced, underappreciated mechanisms of both normal aging and enhanced longevity.
Functional overlap of inborn errors of immunity and metabolism genes defines T cell metabolic vulnerabilities.
Patterson AR, Needle GA, Sugiura A, Jennings EQ, Chi C, Steiner KK, Fisher EL, Robertson GL, Bodnya C, Markle JG, Sheldon RD, Jones RG, Gama V, Rathmell JC.
Sci Immunol. 2024 Aug 16;9(98):eadh0368. doi: 10.1126/sciimmunol.adh0368. Epub 2024 Aug 16.
Large language models facilitate the generation of electronic health record phenotyping algorithms.
Yan C, Ong HH, Grabowska ME, Krantz MS, Su WC, Dickson AL, Peterson JF, Feng Q, Roden DM, Stein CM, Kerchberger VE, Malin BA, Wei WQ.
J Am Med Inform Assoc. 2024 Sep 1;31(9):1994-2001. doi: 10.1093/jamia/ocae072.
Defining documentation burden (DocBurden) and excess DocBurden for all health professionals: A scoping review.
Levy DR, Withall J, Mishuris RG, Tiase V, Diamond CJ, Douthit B, Grabowska M, Lee R, Moy A, Sengstack P, Adler-Milstein J, Detmer DE, Johnson KB, Cimino JJ, Corley ST, Murphy J, Rosenbloom T, Cato K, Rossetti SC.
Appl Clin Inform. 2024 Aug 13. doi: 10.1055/a-2385-1654. Online ahead of print.
Expanded profiling of WD repeat domain 5 inhibitors reveals actionable strategies for the treatment of hematologic malignancies.
Meyer CT, Smith BN, Wang J, Teuscher KB, Grieb BC, Howard GC, Silver AJ, Lorey SL, Stott GM, Moore WJ, Lee T, Savona MR, Weissmiller AM, Liu Q, Quaranta V, Fesik SW, Tansey WP.
Proc Natl Acad Sci U S A. 2024 Aug 27;121(35):e2408889121. doi: 10.1073/pnas.2408889121. Epub 2024 Aug 21.
Jump-starting chimeric antigen receptor-T cells to go the extra mile with nanotechnology.
Chada NC, Wilson JT.
Curr Opin Biotechnol. 2024 Aug 20;89:103179. doi: 10.1016/j.copbio.2024.103179. Online ahead of print.