In August's #EditorsChoice, Gianna Maggiore, @haozhulab.bsky.social & co showed strong clinical potential in reducing #HepatocellularCarcinoma by targeting the actin-binding protein anillin via #siRNA knockdown in #MouseModel.
⚡ doi.org/10.1242/dmm....
📰 doi.org/10.1242/dmm....
That’s a wrap on the past 12 months, with even more #relentlessdiscovery to come in 2026. cri.utsw.edu/discoveries/
@seanjmorrison.bsky.social
@rjdlab.bsky.social
@haozhulab.bsky.social
🧪 #stemcells #regeneration #CancerResearch #metabolism #NYE2025 #NYE2026
ICYMI, there's a new project CRI's @haozhulab.bsky.social will collaborate on: trying to create artificial livers. Read more ⬇️ #relentlessdiscovery #CRIcollaboration 🧪
www.utsouthwestern.edu/newsroom/art...
Henry De Belly, Ph.D., stands in an empty office, with blanks walls and an empty desk, and arms outstretched.
🚨NEW PI ALERT🚨 @henrydebelly.bsky.social is in the house, and look at that *fresh* new office. Clean slate for his next #relentlessdiscovery in CRI's Tissue Regeneration Program (TRP). Onward! Read more about his new lab 👉 cri.utsw.edu/faculty/henr...
🧪 @haozhulab.bsky.social
ONLINE now in @cellpress.bsky.social: A review by CRI's @haozhulab.bsky.social about their #relentlessdiscovery and how somatic mutations are becoming a key discovery engine for disease genetics. 🧪 Read more ⬇️
www.cell.com/cell/fulltex...
new out in Nature, targeting FSP1 to trigger ferroptosis
www.nature.com/articles/s41...
www.nature.com/articles/s41...
ONLINE NOW in @science.org: DeBerardinis Lab discovers protein regulating balance between purine nucleotide production pathways. 🧪
Read more ➡️ cri.utsw.edu/deberardinis...
🔖 full breakdown ⬇️
ONLINE NOW in @science.org: @haozhulab.bsky.social discovers location matters for liver cancer's origins. 🧪
Read more ⬇️ cri.utsw.edu/zhu-lab-show...
🔖 @haozhulab.bsky.social's breakdown ➡️ x.com/Zhu_Lab/stat...
#relentlessdiscovery
![siCdk1 and siAnln decreased tumor burden in the DEN/PB HCC model. (A) Schematic overview of DEN/PB mouse model. At 2 weeks of age, male mice on the C3H strain background were given a single injection of DEN (25 mg/kg) 4 weeks before the start timepoint (-4w). At 6 weeks of age, mice were placed on 0.05% PB drinking water [start timepoint of 0 weeks (0w)]. Mice were injected with siRNA every other week starting at 12 weeks of age (6w), for a total of nine doses (with 5 mg/kg per dose) and sacrificed 1 week after the final dose (23w). (B) Liver weights for DEN/PB mice at 23 weeks after starting PB water, i.e. the final time point. (C) Liver-to-body-weight ratio for DEN/PB mice at the final time point. (D) Representative images of livers from DEN/PB mice at the final time point. (E) Surface tumor numbers were quantified using front and back images of each liver. (F) Representative immunofluorescence images of DEN/PB livers obtained from mice as indicated. Staining was against GS (red) to indicate the degree of WNT activation. Tumors are outlined by yellow dashed lines. One GS+ tumor was seen in the PBS group. Nuclei were stained with DAPI (blue). Scale bars: 800 μm. For panels B, C and E, the P-values with respect to the PBS group are shown above each group.](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:5jupfg23qpjk2643o6aeftly/bafkreia346vromeksdvvhk4ikwhmd5jzwh35ijdqviiprwfwklidcshhqm)
siCdk1 and siAnln decreased tumor burden in the DEN/PB HCC model. (A) Schematic overview of DEN/PB mouse model. At 2 weeks of age, male mice on the C3H strain background were given a single injection of DEN (25 mg/kg) 4 weeks before the start timepoint (-4w). At 6 weeks of age, mice were placed on 0.05% PB drinking water [start timepoint of 0 weeks (0w)]. Mice were injected with siRNA every other week starting at 12 weeks of age (6w), for a total of nine doses (with 5 mg/kg per dose) and sacrificed 1 week after the final dose (23w). (B) Liver weights for DEN/PB mice at 23 weeks after starting PB water, i.e. the final time point. (C) Liver-to-body-weight ratio for DEN/PB mice at the final time point. (D) Representative images of livers from DEN/PB mice at the final time point. (E) Surface tumor numbers were quantified using front and back images of each liver. (F) Representative immunofluorescence images of DEN/PB livers obtained from mice as indicated. Staining was against GS (red) to indicate the degree of WNT activation. Tumors are outlined by yellow dashed lines. One GS+ tumor was seen in the PBS group. Nuclei were stained with DAPI (blue). Scale bars: 800 μm. For panels B, C and E, the P-values with respect to the PBS group are shown above each group.
In this Editor's Choice, Maggiore, Zhu @haozhulab.bsky.social and colleagues reveal the high clinical potential of GalNAc-siRNA-based strategies for preventing hepatocellular carcinoma development in high-risk individuals, particularly through targeting ANLN. doi.org/10.1242/dmm....
#HCC #cancer
Conceptually, selection of somatic mutations that increase clone fitness can predict therapeutic efficacy-BUT some mutations cause conflict between clone and organism. Thanks to our key UK collaborators David Savage, Peter Campbell, Matt Hoare, and contributors from @cri-utsw.bsky.social 8/8
Consistently, Tbx3 KO protected against, and overexpression worsened fatty liver. This is because Tbx3 KO resulted in more VLDL-triglyceride secretion, which moves lipids from the liver to the rest of the body. Consequently, mice suffered from high blood triglyceride levels. 7/8
Loss of function TBX3 mutant clones expand in mice and humans with fatty livers. This suggests that these mutations protect hepatocytes from lipid-induced toxicity. 6/8
The second paper/concept is that some somatic mutations can appear to benefit the clone or organ, but have negative effects for the organism. Congrats to Greg Mannino on his first paper! 5/8 www.jci.org/articles/vie...
Consistently, liver-wide CIDEB inhibition was more protective against disease mechanisms that led to more clone expansion, suggesting that patients with more or larger CIDEB mutant clones might expect greater benefit from CIDEB inhibition. 4/8
CIDEB mutant clones expand more in the context of some fatty liver diets, but not others. This suggests that CIDEB mutations are protective of hepatocytes, but to varying degrees depending on diet type or genetic cause of disease. 3/8
These illustrate 2 concepts about somatic mutations and how they inform therapeutic strategies. The 1st concept is that some mutations predict effective therapies that benefit the individual as well as the clone. Congrats Qiyu Zeng @satishpatel.bsky.social 2/8 www.sciencedirect.com/science/arti...
Introducing 2 new papers from my lab on somatic mutations in liver disease. The 1st is about a mutated gene that leads to improved clone fitness and organismal health (CIDEB). The 2nd is about a mutated gene that leads to improved clone fitness but worse overall health (TBX3). 1/8
Today's #thursdaymotivation is courtesy CRI's @haozhulab.bsky.social: Congrats Gianna Maggiore for your successful #dissertationdefense! Dr. Maggiore's family and lab mates joined to celebrate. Next steps: summertime fun & finishing her M.D. 🎉 #relentlessdiscovery
