Illuminating keratinocyte cell biology @DermatologyUW to understand epidermal differentiation/tissue homeostasis and how they are compromised in skin disease.
Joined October 2021
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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.
Images for #FluorescenceFriday: Our @NikonUSA
@Yokogawa_LS confocal🔬lets us visualize organelle dynamics (ER shown here) within live multi-layer organotypic human epidermis to illuminate the biology of keratinocyte differentiation, which is compromised in skin barrier disorders.
Always an optimistic time heading into Spring and looking forward to more lab outings. Outstanding talk today from Jess @UWM3D PhD student @UWMedicine who finished a super successful Winter rotation. Excited to welcome Alex & Aaron to @SimpsonLabUW rotating in the Spring quarter.
Must celebrate days when everything works because they don't come often. Esp love getting great data on a Friday. Credit to Afua for getting our KO blot protocol just right & @UWM3D student Jess for beautiful images in time for #FluorescenceFriday. @DermatologyUW @UWMedicine
Congrats to CJ Johnson, med student @uwsomwwami, on winning a travel award to proudly represent @SimpsonLabUW at the Western Student & Resident Medical Research Forum in sunny Carmel, CA 😎 Great talk on how ER stress regulates epidermal differentiation @UWMedicine @DermatologyUW
Happy holidays & new year from @SimpsonLabUW @DermatologyUW @UWMedicine! Looking fwd to a 2023 full of exciting science, fruitful collaborations & in-person mtgs across the globe (image crop of organoid epidermis; green=keratin, red=DNA; @NikonUSA Ti2 w/@Yokogawa_LS W1 confocal).
Celebrating the end of a great yr @DermatologyUW @UWMedicine. Hard to believe this time last yr it was a lab of 1. Lucky to have enthusiastic scientists @SimpsonLabUW who make me a proud #NewPI. Still #hiring a #postdoc if you’d like to join us in Seattle: apply.interfolio.com/113194
Congrats to CJ for winning the medical student prize for his poster @UWMedicine Montana site summarizing his summer project🔬🧫on the role of #autophagy in epidermal differentiation. Thanks for representing @SimpsonLabUW & @DermatologyUW in the greater WWAMI region. Very proud🤩
If you've ever had to troubleshoot a lab protocol that suddenly stops working, then you know TFW you finally get a DNA curve like this after wks of failed preps🥳 Special thanks to Mariko, cloning master from @ErikaHolzbaur lab, for helping us figure it out...was the antibiotic🤦♂️
