Rosalie Lawrence, PhD

Dr. Lawrence's lab studies molecular mechanisms via which cellular stress responses sense metabolites and coordinately adjust cellular metabolism. Specifically, they study structural and biochemical mechanisms via which the Integrated Stress Response pathway is activated. They then build on this understanding to engineer cellular models that display chronic cellular stress phenotypes known to contribute to therapeutic resistance in cancers ranging metastatic breast cancer from glioblastoma. For example, they have built models of chronic-ISR signalign in iPSC-derived astrocytes, to decipher fundamental mechanisms via which chronic stress signaling rewires astrocyte metabolism, and contributes to astrocytomas including glioblastoma. Dr. Lawrence and her lab use biochemical, co-culture modeling, and collaborative in vivo approaches to test the role of stress-driven metabolic remodeling on specialized cell function.

Lawrence, R.E., Shoemaker, S.R., Deal, A. et al. A helical fulcrum in eIF2B coordinates alosteric regulation of stress signaling. Nat Chem Biol 20, 422–431 (2024). Nature Chemical Biology

Samelson AJ, Ariqat N, McKetney J, Rohanitazangi G, Bravo CP, Bose R, Travaglini KJ, Lam VL, Goodness D, Dixon G, Marzette E, Jin J, Tian R, Tse E, Abskharon R, Pan H, Carroll EC, Lawrence RE, Gestwicki JE, Eisenberg D, Kanaan NM, Southworth DR, Gross JD, Gan L, Swaney DL, Kampmann M. CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis. bioRxiv [Preprint]. 2024 Nov 4:2023.06.16.545386. doi: 10.1101/2023.06.16.545386. PMID: 37398204; PMCID: PMC10312804.

Morgane Boone, Lan Wang, Rosalie E Lawrence, Adam Frost, Peter Walter, Michael Schoof (2022) A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation eLife 11:e76171. https://doi.org/10.7554/eLife.76171