Peds Heme Onc Fellow @Stanford/@LPCH | Formerly @UCSFPediatrics | MD/PhD @StanfordMed @mbarnalab | @PDSoros | Physician-Scientist | Gene regulation, RNA bio

@geraldctiu.bsky.social
Joined February 2018
Many of you don't understand how serious this is, so let me break it down. In computer science there is a famous kind of puzzle called 3-SAT. You are given a long list of yes-or-no switches and a set of rules about how they must be arranged, and you have to find a combination that satisfies every rule. The obvious way to solve it is to try every combination, but each new switch doubles the number of possibilities, so a puzzle with a few hundred switches would take longer than the age of the universe to brute force. For decades, the smartest people in the field found clever tricks that made this a little faster, but every trick still hit the same wall: the time required kept exploding as the puzzle grew. About 25 years ago, two computer scientists, Russell Impagliazzo and Ramamohan Paturi, working with Francis Zane, turned that wall into a formal idea. They proposed the Exponential Time Hypothesis, which says this explosion is not a failure of human cleverness but a law of nature. No algorithm, however brilliant, will ever solve 3-SAT without the time blowing up exponentially. Nobody could prove it, but almost everyone believed it, and it became one of the foundations of modern computer science. Researchers used it as a measuring stick. If you could show that solving some other problem quickly would also crack 3-SAT quickly, you had shown that problem was hopelessly hard too. Hundreds of papers, across scheduling, graphs, logic and much more, rest on this one assumption. Now an internal AI model at OpenAI claims to have broken it. It says it found an algorithm that solves these puzzles meaningfully faster than the hypothesis allows, and it has checked the proof in a computer verification system called Lean. And here is the remarkable part: the very people who proposed the hypothesis, Impagliazzo and Paturi, along with MIT's Ryan Williams, are now leading the public review of whether a machine has disproved their own idea. So what happens next? If the disproof holds, a large part of theoretical computer science has to be revisited. Every result that said "this problem cannot be solved faster, assuming ETH" loses its foundation, and researchers will have to work out which of those walls were real and which were simply where we stopped looking. It does not mean everything becomes easy. The new algorithm is still slow in absolute terms and this is not the famous P versus NP problem being solved. But it means our map of what is possible was wrong in a place we were very confident about, and it was an AI that redrew it. If the disproof fails, the hypothesis survives and the field breathes out, but we will still have watched an AI produce serious, checkable work on one of the deepest questions in the discipline, closely enough that the founders of the idea had to take it seriously. Either way, something has shifted.
An internal model at OpenAI has produced a claimed refutation of ETH! Russell Impagliazzo, Mohan Paturi, and I have been asked to help organize an open and independent examination of this claim. 1/4
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Gerald Tiu retweeted
Thrilled to share my freshly "baked" Baker lab paper. We took a bottom-up approach to designing transcriptional regulators. Instead of relying on natural activation domains, we designed compact proteins that recruit specific cofactors. Activators for now, repressors to come!
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Ever wonder if tRNAs can regulate the identity of a cancer cell? @HsiehLab @FredHutch postdoc @yeonsookim_phd did and discovered a single tRNA that can control lineage dependency and drug sensitivity in prostate cancer published today @Nature: nature.com/articles/s41586-0…
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BREAKING NEWS The 2026 #NobelPrize in Physiology or Medicine has been awarded to Karl Deisseroth, Peter Hegemann and Georg Nagel “for their discoveries concerning light-gated ion channels and optogenetics.”
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Cell–cell interactions are key to all biological processes, but there hasn't been a good way to perform inter-cellular screens for genetic regulators of these interactions in vivo. We developed match-seq (multiplexed associative tagging of cell interaction histories) - using engineered virus-like particles to transfer barcoded mRNAs from 'sender' to neighboring 'receiver' cells, so you can reconstruct cellular interactions with sequencing alone, no imaging required. We coupled match-seq with CRISPR + scRNA-seq in cancer, revealing cancer-immune interaction neighborhoods at scale, and new cancer genes that can be targeted for tumor rejection via immune cell interactions. Led by the brilliant @peterdu_ with Bassik lab! biorxiv.org/content/10.64898…
CRISPR screens are great at telling you what a gene is doing inside your cells. But what if you're interested in what's happening to its neighbors? Today, I'm excited to share match-seq, a new method that deciphers cell-cell interactions using barcoded RNA transfer. 1/9
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As usual, Zvi has the best take on the Navier-Stokes proof, Theres a lot of fog and confusion, but the real story here is that it didn’t even take OpenAI two weeks to train a model that’s a step change above Astra, at least when it comes to math capability.
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Gerald Tiu retweeted
We’re sharing a solution to the Navier-Stokes Millennium Prize Problem, one of the deepest problems at the frontier of mathematics. The proof was produced by a group of agents, using an OpenAI next-generation model significantly more capable than GPT-6 Astra. The problem concerns whether the description of smooth three-dimensional fluid motion modeled by the Navier-Stokes equations can break down. It has remained unresolved for roughly 90 years.
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Very cool and natural direction for genetics. @KroganLab identified binders of 100 ASD genes and tested missense variants for their effects on protein-protein interactions. A diversity of mechanisms can emerge from this. Very impressive. science.org/doi/10.1126/scie…
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Excited to share my PhD work, now on @bioRxiv! 🎓🦠Viruses are packed with small ORFs with unknown function. At @JswLab w/ collaborators, we built a pan-viral microprotein atlas that uncovered the oncogenic activity of BNLF2b, an EBV gene linked to cancer. biorxiv.org/content/10.64898…
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1/2 Garcia Lab preprints out now - "Functional Pairing of TCR-pMHC Interactomes by Single-cell Clonal Expansion" led by @LiuDaisyLiu. Super cool tech!
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Tackling a 60-year-old challenge in quantum chemistry: making density functional theory scale nearly linearly with system size. This has huge implications for opening the door to realistic systems that have traditionally been too expensive to simulate. AI has attempted to accelerate these calculations, but models generally struggle to extrapolate, particularly to systems larger than those seen during training. Unlike text or images, quantum-mechanical training data is extremely expensive to generate. We present a single unified AI model that performs quantum-mechanical simulations of both molecules and materials in quasi-linear time. Using a novel Fourier neural operator variant, we learn the underlying Kohn–Sham equation map to produce physics-informed, self-consistent answers. Unlike prior AI approaches that directly predict chemical properties, our model works through intermediate steps to improve difficult predictions, resembling inference-time reasoning in large language models. To demonstrate its scalability, we run a self-consistent calculation of a magnesium dislocation with about 80k electrons on a single GPU, which previously required about 7k GPUs. tensorlab.cms.caltech.edu/us… @DanishK42 @Caltech
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Gerald Tiu retweeted
Transcription Factors are central to cellular identity and function. The human genome currently contains ~1600 of them. But could there be productive human transcription factors that have not evolved? Out today in Cell, a tremendously talented graduate student Oliver Takacsi-Nagy @Oli_TN, together with the @Satpathology Lab, determined to find out. (1/10) authors.elsevier.com/sd/arti…
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Human protein-coding genes evolved from old parts - reconfigured domains from ancestral genes. We can screen short-sequence evolution at scale using mutagenesis, CRISPR, etc, but we had no way to do the same for domain-level evolution. Happy to share our work developing DESynR genes today in @CellCellPress: scalable synthesis and functional screening of thousands of new human genes, built from old parts. DESynR transcription factors outperform native factors and dramatically improve CAR T cell function. A team effort led by the incredible Oliver Takacsi-Nagy! @parkerici @CancerResearch @TheMarkFdn cell.com/cell/fulltext/S0092…
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Four years ago, a mystery case led Core Investigator @jvpluv to discover a new diagnosis (ABCD). Today his team published one of the largest clinical surveys of unexplained spinal cord disease to date in @JAMANeuro, finding ABCD in roughly half of patients.
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Gerald Tiu retweeted
Chromatin has long been proposed to "store" memory related information; but what kind of information, contents or rules does it hold? Check out our new preprint: biorxiv.org/content/10.64898… 1/13
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Dyna-1 is now published in @Nature! Since this preprint thread 18 months ago, there's prospective experimental validation and more! nature.com/articles/s41586-0… Many congratulations to coauthors @ginaelnesr @DorotheeKern and the whole team!
Protein dynamics was the first research to enchant me >10yrs ago, but I left in PhD bc I couldnt find big expt data to evaluate models. Today w @ginaelnesr, I'm thrilled to share the big dynamics data I've been dreaming of, and the mdl we trained: Dyna-1. rb.gy/de5axp
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