Thrilled to share our new paper: SLC33A1 is the long-sought ER GSSG exporter, maintaining redox homeostasis in the ER. Huge congratulations to my co-first author @shanshanliu1218 and my PIs @KivancBirsoy and @HiteLabMSKCC for leading this work. nature.com/articles/s41556-0… 🧵 1/9

1/ Excited to share our new paper in @NatMetabolism: cysteine excess triggers a mitochondrial iron-dependent cell death. nature.com/articles/s42255-0…

Why is glutathione, rather than cysteine, the major cellular thiol? Our new work by @ToshiNakamura51 suggests unlike other amino acids, excess cysteine is intrinsically toxic to mammalian cells via mitochondrial iron accumulation. @RockefellerUniv nature.com/articles/s42255-0…

Moderna/Merck just ran a 1,137-patient Phase 3 trial where every single dose was unique to that patient's tumor. It worked. The pipeline: surgical resection → whole exome + RNA sequencing → ML neoantigen ranking → mRNA encoding up to 34 patient-specific targets → manufactured and shipped in 8 weeks. One drug, different sequence for every patient. The ML step is worth to note: the algorithm ingests WES + RNA-seq to identify somatic mutations, then predicts which of those will actually be immunogenic, ie, displayed on tumor cell surface and trigger a T-cell response. It's designed to keep learning from accumulated clinical and immunogenicity data across patients, not just per-patient. INTerpath-001 (Stage IIB-IV resected melanoma, 2:1 randomized): combination with pembrolizumab beat Keytruda alone on both primary (RFS) and key secondary (DMFS) at interim. Phase 2b at ASCO 2026 showed 49% reduction in recurrence/death, 59% in distant metastasis/death at 5 years. Phase 3 confirmed both. What this validates: — tumor-specific neoantigen prediction by ML works in a blinded trial at scale — 8-week personalized mRNA manufacturing is operationally real — effect is additive on PD-1 blockade, not redundant This is first positive Ph3 for individualized neoantigen therapy. First positive Ph3 for any mRNA cancer therapeutic. What a great time to live in!! This is the best time for AI & biotech!

Excited to share our new work! We identified SLC33A1 as the major ER GSSG exporter that maintains redox balance in the ER lumen.

Our new work by @shanshanliu1218 and @gadmark addresses a fundamental question: how does ER maintain its unique oxidizing environment, while rest of the cell is reducing? Here, we identify SLC33A1 as the major ER GSSG exporter in mammalian cells. nature.com/articles/s41556-0…

In @NatureCellBio: @KivancBirsoy's lab has discovered that the antioxidant glutathione plays a vital role in maintaining smooth operations of a protein-producing hub in the cell called the endoplasmic reticulum by acting as a protein “proofreader.” 🔗: bit.ly/3Ow8lxM

Check out this amazing work by @shanshanliu1218 and @gadmark !

Check out this impressive work and #tweetorial from @gadmark and @shanshanliu1218! If you’re interested in organellar metabolism and metabolite transport, this is a landmark paper on ER redox metabolism and transport👇

Was an honor to contribute to this tremendous study co-led by the brilliant duo of @gadmark and @shanshanliu1218. Check out the thread below to learn more about how SLC33A1 works to maintain ER redox balance!

Read my latest newsletter on big pharma’s commercials during tonight’s #SuperBowl . And don’t forget to subscribe markgad.beehiiv.com/p/pharma…

California state reservoir levels are now at 130% of normal, holding 7 trillion gallons of water. Remarkable.