We recently started studying the cellular mechanisms of a #skin #blistering disorder called #Grover disease and I think we actually found him in one of our confocal microscopy images! Happy Friday from @SimpsonLabUW. Image credit to CJ Johnson in our lab 😁🔬🧫#FluorescenceFriday

Kudos to lab members @ZaverShivam & Afua Tiwaa and many thanks to our amazing collaborator labs @briancapell @PennMedicine and Johann Gudjonsson @umichmedicine. Thanks also to @PennSbdrc @NIH_NIAMS @UWISCRM for supporting our lab to do this work @UWMedicine @DermatologyUW (7/7).

Inhibiting MEK (using a drug class that is already FDA-approved for other diseases) in sheets of SERCA2-deficient keratinocytes restored their cohesion and supports our proposal that targeting this pathway may be a novel treatment to halt skin blistering in Darier disease (5/7)

Importantly, we corroborated these results in skin biopsies from patients with Darier disease. Again, we found that ERK was hyperactive, suggesting this signaling pathway might be responsible for reducing adhesion among the keratinocytes to cause skin blistering in patients (4/7)

We grew gene-edited keratinocytes as organoid epidermis to model Darier disease in 3D tissue & aimed to find new treatment strategies. Combining RNAseq, proteomics & confocal microscopy we found SERCA2 loss led to upregulation of the MAP kinase signaling pathway via MEK/ERK (3/7)

Using CRISPR/Cas9 editing in human keratinocytes (the cells that make up our outer skin barrier, the epidermis), we deleted the disease-linked gene ATP2A2, which encodes a calcium pump (SERCA2) that lives in the endoplasmic reticulum (2/7)

Thrilled to share the 1st @SimpsonLabUW research publication online @JCI_insight. We generated a pre-clinical model of Darier disease, a rare genetic skin blistering disorder that I see in my clinic and for which there are no FDA-approved therapies (1/7) insight.jci.org/articles/vie…

Beautiful week in Seattle☀️😎for a fun lab outing @UWMedicine. It’s been a great summer so far with this outstanding crew of scientists from @uwsomwwami @UWM3D and @DermatologyUW. Proud of their hard work to churn out exciting data and fuel new grant ideas💡🔬🧫🦠🧬

Great week for #confocal #microscopy🔬data from live human #epidermal #keratinocytes🧫@SimpsonLabUW @DermatologyUW. Credit to our outstanding students for these images of actin, ER, lysosomes, and microtubules🤩Happy Friday! #FluorescenceFriday

Excited 🥳 to get official notice for 1st (non-transferred) @NIH_NIAMS grant to @SimpsonLabUW @UWMedicine. Via this R03, we’ll use live microscopy of organoid human skin to learn how keratinocytes use #autophagy to remodel/degrade organelles like ER to form the epidermal barrier.

Beautiful day for a @SimpsonLabUW happy hour! 😎 Of course, this was only after our super serious journal club 🤓📚🔬🧬

Excited to share our results soon @ISID2023Tokyo about our recent work to understand the dynamic behavior of the ER during human epidermal tissue differentiation.