Research & Clinical Summary

Dr. Simpson launched a research laboratory at the University of Washington in 2021 to study epidermal differentiation and how it is compromised in dermatologic disease. The Simpson Lab focuses on the role of autophagy and organelle degradation in human keratinocytes and how these cellular pathways drive maturation and homeostasis of the epidermal tissue. Using an organotypic model of human skin coupled with advanced microscopy, his lab can visualize the live tissue at the level of single organelles to better understand how the epidermis forms and how disease-associated mutations disrupt the tissue. Ultimately, the Simpson Lab aims to identify novel treatment strategies to promote epidermal tissue regeneration after skin injuries and to restore skin barrier function in inherited and currently incurable dermatologic diseases.

The Simpson Lab is currently accepting M3D students for first-year quarterly rotations.

Publications

Zaver SA, Sarkar MK, Egolf S, Zou J, Tiwaa A, Capell BC, Gudjonsson JE, Simpson CL. Targeting SERCA2 in organotypic epidermis reveals MEK inhibition as a therapeutic strategy for Darier disease. JCI Insight. 2023 Sep 22;8(18). doi: 10.1172/jci.insight.170739. PMID: 37561594

Zaver SA, Johnson CJ, Berndt A, Simpson CL. Live Imaging with Genetically Encoded Physiologic Sensors and Optogenetic Tools. J Invest Dermatol. 2023 Mar;143(3):353-361.e4. doi: 10.1016/j.jid.2022.12.002. PMID: 36822769

Simpson CL, Tokito MK, Uppala R, Sarkar MK, Gudjonsson JE, Holzbaur ELF. NIX initiates mitochondrial fragmentation via DRP1 to drive epidermal differentiation. Cell Rep. 2021 Feb 2;34(5):108689. doi: 10.1016/j.celrep.2021.108689. PubMed PMID: 33535046

Moore AS, Coscia SM, Simpson CL, Ortega FE, Wait EC, Heddleston JM, Nirschl JJ, Obara CJ, Guedes-Dias P, Boecker CA, Chew T-L, Theriot JA, Lippincott-Schwartz J, Holzbaur EL. Actin cables and comet tails organize mitochondrial networks in mitosis. Nature. 2021 Mar; 591(7851): 659-664. PMID: 33658713

Egolf S, Zou J, Anderson A, Simpson CL, Aubert Y, Prouty S, Ge K, Seykora JT, Capell BC. MLL4 mediates differentiation and tumor suppression through ferroptosis. Sci Adv. 2021 Dec 10;7(50):eabj9141. doi: 10.1126/sciadv.abj9141. Epub 2021 Dec 10. PMID: 34890228

Lin-Shiao E, Lan Y, Coradin M, Anderson A, Donahue G, Simpson CL, Sen P, Saffie R, Busino L, Garcia BA, Berger SL, Capell BC. KMT2D regulates p63 target enhancers to coordinate epithelial homeostasis. Genes Dev. 2018 Jan 15;32(2):181-193. doi: 10.1101/gad.306241.117. Epub 2018 Feb 12. PubMed PMID: 29440247

Moore AS, Wong YC, Simpson CL, Holzbaur EL. Dynamic actin cycling through mitochondrial subpopulations locally regulates the fission-fusion balance within mitochondrial networks. Nat Commun. 2016 Sep 30;7:12886. doi: 10.1038/ncomms12886. PMID: 27686185