Excited to share my PhD story, out in @Dev_Cell today: We show that Nrf2-driven induction of the pentose phosphate pathway stimulates liver regeneration after injury. Thanks to @DrAndrewCox, @MAF_Dawson, Cox Lab and @TheDawsonLab members! Incoming 🧵1/9.

#zebrafish researchers, @ZDMSociety is hosting #ZDM18 in Boston this year (Oct 13-15). One of my favourite conferences with interesting talks and is always fun! Abstract submissions and early bird registrations close on July 11. Hope to see you there!.

RT @whitefishlab: Lipid droplets are commonly seen in cancer cells. In our new paper, @Eleanor_M_Johns characterizes the lipid droplet "co….

RT @BenLai_Taiwan: One of the highlights of the #ZDM17 has to be the fruitful discussion during DEI lunch with people from (almost) all con….

Thanks for the opportunity to share this work! An exciting story is brewing, and it started from Maya Emmons-Bell’s surprising observation where the regenerative microenvironment of the caudal fin is tumour suppressive. Hope to share the full story at the next ZDM 😊.

#ZDM17 — what a conference 🤩 Thank you to @ZDMSociety for an incredible few days of science (and party)! I learnt so much from all the talks and chats, and was in awe of the keynotes (@LeilaAkkari1/@Planaria1). Extra special to catch up with the Cox Lab 🥹

RT @ZebrafishRock: It wouldn’t be a fish meeting without a Twitter/X photo-op! #RockOn #ZDM17 @ZDMSociety

A refreshing perspective on the importance of curiosity-driven and basic science.

RT @AusAmbCroatia: It felt like a Saturday afternoon in suburban Australia when the Oxford Uni AFL club took on local AFL teams in Zagreb.….

RT @PijpersLizzy: Exciting news! First first author paper is here! Epigentic targeted CRISPR screening reveals PRMT1 as a negative regulato….

Can’t believe it’s been 4 weeks since I started as a post doc in @whitefishlab, @Ludwig_Cancer in Oxford – where I’ll be exploring the relationship between regeneration and melanoma development 🧫🐟! . Also feeling grateful to have found the best AFL team in the UK @OUARFC 🤩

Collectively we have gained insights into metabolic reprogramming during regeneration. We hope that our studies will provide possible therapeutic avenues to stimulate regeneration in patients with acute liver failure.

Quantification of individual BrdU+ hepatocytes in vivo identified that NS supplementation improved hepatocyte proliferation significantly in Nrf2KO animals. Collectively, we demonstrated that Nrf2-regulated PPP promotes liver regeneration through nucleotide biosynthesis. 9/9.

This was suppressed by the inhibition of the PPP’s rate limiting enzyme, G6PD. As PPP products stimulate both antioxidant defence and nucleotide biosynthesis, we supplemented APAP-exposed zebrafish with the antioxidant N-acetyl cysteine and a cocktail of deoxynucleosides. 8/9.

@DrAndrewCox @MAF_Dawson @MrTonylope @aj12aj @BalicJesse @yihchih @BladenCerys @TheDawsonLab Nrf2 activation following liver injury induced genes involved in the pentose phosphate pathway (PPP) in an evolutionarily conserved manner. Through in vivo imaging, we show that hepatocytes rapidly proliferate following injury. 7/9.

@DrAndrewCox @MAF_Dawson @MrTonylope @aj12aj @BalicJesse @yihchih @BladenCerys @TheDawsonLab SLAM-ITseq revealed an initial metabolic switch from fed to the fasted state in hepatocytes, that preceded the activation of the Nrf2 pathway. We found that Nrf2-deficient animals had poorer overall survival following liver injury compared to their WT counterparts. 6/9.

@DrAndrewCox @MAF_Dawson @MrTonylope @aj12aj @BalicJesse @yihchih @BladenCerys @TheDawsonLab Using the SLAM-Tseq approach, we bypassed laborious cell-enrichment steps (as hepatocytes only make up ~3% of a whole zebrafish) and identified distinct temporal dynamics of nascent gene expression in hepatocytes following liver injury. 5/9.

@DrAndrewCox @MAF_Dawson @MrTonylope @aj12aj @BalicJesse @yihchih @BladenCerys @TheDawsonLab Hepatocytes are the main contributors to liver regeneration. Consequently, we developed a zebrafish model wherein hepatocyte-specific expression of uracil phosphoribosyltransferase (UPRT) allowed us to perform metabolic labelling of nascent transcripts in vivo (SLAM-ITseq). 4/9.

@DrAndrewCox @MAF_Dawson @MrTonylope @aj12aj @BalicJesse @yihchih @BladenCerys @TheDawsonLab Liver injury upon drug exposure such as acetaminophen (APAP) can occur rapidly, overwhelming the capacity to regenerate and resulting in acute liver failure. We were curious to see the early transcriptional responses following liver injury. 3/9.

First and foremost, thank you to everyone who made this possible, in particular, @DrAndrewCox and @MAF_Dawson. In addition to Talhah, @MrTonylope , Andrea, @aj12aj, @BalicJesse, @yihchih and @BladenCerys and the rest of the Cox Lab and @TheDawsonLab. 2/9.