@landau_labi
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Somatic evolution, cancer genomics (Weill Cornell/NYGC) // Chair, department of Systems and Computational Biology (WCM) // Oncologist (NYP)
New York, USA
Joined August 2015
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The rumors are true! I am beyond excited to take on this new adventure as the inaugural chair of the Systems and Computational Biology (SCB) Department at @WeillCornell thread 👇
Congratulations to our @WCMEnglanderIPM colleague Dr. Dan Landau (@landau_lab) on being named Inaugural Chair of the Department of Systems and Computational Biomedicine @WeillCornell! #ArtificialIntelligence #LiquidBiopsy #genomics #biomedicine #DreamBig
news.weill.cornell.edu/news/…
Dan Landau retweeted
Congratulations to the pioneer who started it all with his momentous discovery that mutant KRAS in cancer can be directly targeted and blocked:
@kevansf @UCSFCancer on winning the @sgpcri Global Prize!
KRAS inhibitors for the win!
#AACRPan26
Dan Landau retweeted
Behold the tolerogenic vaccine lives !
Induction of immunity in absence of costimulation to antigen-specifically block #multiplesclerosis #autoimmunity.
science.org/doi/10.1126/scie…
Dan Landau retweeted
Excited to share our new paper, out today in @ScienceMagazine! We developed senescence-modulating nanoparticles (SMNPs) that target P-selectin+ pathogenic senescent-like macrophages in fibrotic tissues and tumors.
science.org/doi/10.1126/scie…
Dan Landau retweeted
So excited to be part of this incredible work out today in @ScienceMagazine on how P-selectin-targeted anti-senescence nanotherapy can fight fibrotic conditions and cancers. Congrats to @LoweLabMSKCC and @hellerlab members and others @MSKCancerCenter!! science.org/doi/10.1126/scie…
Dan Landau retweeted
Congrats to @KleinLabHMS , love it when great things happen to great people!
Congratulations to Cellular Intelligence Scientific Co-Founder Allon Klein @KleinLabHMS on being named a 2026 Schmidt Sciences @schmidtsciences Polymath.
Allon is Professor of Systems Biology at Harvard Medical School @harvardmed, working where physics, computation, and biology combine into one discipline. His research on how cells make decisions is foundational to what we're building at CI.
Congratulations as well to Allon’s fellow Polymaths, and to Schmidt Sciences for backing bold science that refuses to stay in one lane.
schmidtsciences.org/2026-pol…
Dan Landau retweeted
Holy Grail or holy sh..t?
Very intriguing results from the PATHFINDER-2 trial with Galleri MCED test - trial does not reach its endpoint (of reducing n of 12 index st 3/4 cancers by 3 yrs) but still… notable separation of stage 4 cancer detection curves at 3 yrs+ so maybe endpoint was overoptimistic/too early?
Despite very high specificity, low prevalence yields more false neg than true pos results so similar to scanxiety…. With MCED tests we will run risk of creating a new emotion: MSAD…
In a trial of a blood-based multicancer early-detection test added to usual care, the incidence of stage III or IV cancer after three rounds of screening did not differ significantly from that with usual care alone. Full NHS-Galleri trial results: nej.md/4xRZN5L
Editorial: A Step in the Search for the Elusive Holy Grail of Early Detection of Cancer nej.md/4cK3UIy
ALT A bar chart from an Original Article published in the New England Journal of Medicine article titled "Effect of Screening with Multicancer Early-Detection Test on Late-Stage Cancer Diagnosis." The chart shows the distribution of the route to cancer diagnosis according to trial group after three annual screening rounds. The trial name, NHS-Galleri, is in parentheses after the title. The NEJM identity sits at the bottom.
Dan Landau retweeted
Mutational signature analysis has become a standard tool in genome analysis. The underlying assumption for conventional NMF (non-negative matrix factorization) is that signatures act independently. But do they? SBS2/13 (APOBEC) usually co-occur, as do repair signatures and others
Dan Landau retweeted
Predicting the effects of genetic or biochemical perturbations in single cells is a task so-called “virtual cells” often engage with.
To learn new biology, we need models that are interpretable, predicting not just the “output” of unseen perturbations but also the stream of events happening in the cell.
Graphs are useful representation of gene interactions and are interpretable because they represent genes as nodes and perturbations as changes in a gene regulatory network. Combination of perturbations can be represented in a biological meaningful way.
Graph Learning models are also efficient to train and less data hungry than classical transformers. But biological graphs are heterophilic, something that classical graph learning does not deal with well.
SPECTRA leverages on Graph Learning combined with frequency-aware graph convolution to predict perturbation cascades on gene regulatory networks from single cell perturbation screens. SPECTRA is interpretable because the model always operates directly at the gene level, explicitly modelling gene-to-gene interactions.
Beyond the predictive power, we tested the computed perturbation cascade has biological meaning.
As a community, we are far from having predictive models that are ready to explore new biology, but we have learned a lot while developing SPECTRA and it is just the starting point to see how far we can push machine learning to simulate biology.
Link of the pre-print below 👇
Dan Landau retweeted
‘Les Rita Mitsouko' on October 13, 1988 in Paris, France. Photo by Robert Doisneau
Dan Landau retweeted
Delighted that our discovery of regulated, naturally occurring RNA phosphorothioates — in which a phosphate in the RNA backbone is replaced by sulfur — is now out! Huge kudos to @maman_alexander for leading this work, and to all our wonderful collaborators. Tweetorial below!
1/ Out today in @CellCellPress 🎉
Collaborating across three continents to study how organisms at the extremes use RNA modifications, we discovered something new: the first natural modification of the RNA backbone, phosphorothioates (PS), and their writers. With @SchragaSchwartz
Dan Landau retweeted
Replying to @landau_lab
Big tree dreams come true thanks to imaginative minds and unique vision like yours. So grateful for the support over these years, for the ideas, and for showing me that everything is possible with team work. Open arms to many more tree dreams! 🌳 Thank you, Dan
Dan Landau retweeted
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…
Dan Landau retweeted
#Review🚨
Read how genotype and phenotype co-evolve during cancer progression with insights from single-cell multimodal technologies and phylogenetic approaches, revealing vulnerabilities in mutant clones.
@TamaraPrietoF @FrancoIzzo85 @landau_lab
📖👇
dlvr.it/TVXsBD
Dan Landau retweeted
Discovery of a rare gene EGFR variant that predisposes to lung cancer, a 25-fold risk among carriers, a risk that exceeds smoking, high-risk seen in non-smokers, on the cover @ScienceMagazine, with trace of origin to a Southern Appalachia founder event
science.org/doi/10.1126/scie…
From Yolanda Castano poems, a parting gift from the brilliant @TamaraPrietoF
Dan Landau retweeted
Inspired by Gibson cloning, we describe prime assembly, now published, for in cellulo targeted integration of gene-sized DNA fragments using prime editing. nature.com/articles/s41586-0…
How does interferon-alpha interfere with clonal evolution in human blood stem cells? We address it here @natureGenet: nature.com/articles/s41588-0…
🎉 Congrats to our super talented students Chhiring Lama, @danielle_isakov! Wonderful collab w/ Ron Hoffman. @WCMC, @WCMCPathology
🧵⤵
Dan Landau retweeted
By far the most honest and heart-felt plea without the usual baseless fearmongering that I have read from a frontier lab researcher. Have been struggling with my thinking about risks, regulation, slow downover the last few months. Pretty convinced the risks cannot be dismissed.
Dan Selsam is a current OpenAI capabilities researcher. (since 2022) He was my boss for a while. He doesn't have a twitter account but has made this public statement of his views on AI risk and sent it to me to share:
Dan Selsam's Personal Statement on AI Risk:
I have been working on AI for over fifteen years, across many different paradigms. I did early work on probabilistic programming languages at MIT, was one of the early developers of the Lean Theorem Prover at Microsoft Research, demonstrated one of the first instances of neural networks learning to reason for my PhD at Stanford, and since joining OpenAI almost five years ago, have helped pioneer chain-of-thought optimization on language models and, more recently, data-efficient pretraining methods.
Like many others, I have become extremely concerned about how far language models have come and the risks that future iterations will pose. I am encouraged by the recent proposals by the leaders of the frontier research efforts to require third-party oversight, and to push for domestic and international coordination to address risks. However, I believe a major consideration has been absent from the public conversation, and that merely pacing the frontier more carefully will not adequately limit the long-term risk.
The crucial and overlooked problem is that the models are becoming so situationally aware that we are losing the ability to evaluate them in contexts where they believe they are not being watched or controlled. Future experiments will tell us almost nothing new about how they would behave if they were truly unconstrained by humans, and what we already know about this is alarming. Models will increasingly seem aligned even when they are not. I will explain my rationale in more detail.
I have always believed that there are computational processes that could be leveraged to accelerate science and solve many of humanity's most pressing problems. I have also believed that there are computational processes that if set in motion, would steer the world in extreme ways beyond our control, leading humanity to a bad or nonexistent future. Both types of processes may be described as AI or ASI, but "AI" is a suitcase word that is often used to hype or confuse. There are many examples in the history of the field where something that was once considered "AI" matures as a subfield and becomes a prosaic, bounded and clearly non-perilous technology, while a new more mysterious approach takes the torch until we understand its scope and the cycle continues.
I had expected language models to follow a similar trajectory. Despite their incredible abilities, the current algorithms seem far inferior to humans in important ways. Most importantly, they still require an extraordinary amount of data to become competent. One could even define intelligence as the efficiency with which one converts experience into competence; by this definition they lag very far behind us. Moreover, once they are trained they are literally frozen in deployment and only learn superficially after that. Sure, the models keep excelling at harder and harder evaluation benchmarks, but their benchmark mastery may partly reflect a limitation on our ability to simulate the kind of novel and even adversarial situations one would encounter in the real world. The critics do have a point here.
That said, I no longer think these present limitations meaningfully limit the amount of risk posed by continued progress in anything like the current paradigm. However data-inefficient the models are currently, and however limiting their anterograde amnesia may be, it does not imply that their ability to steer the world will not continue to rapidly increase.
Human researchers may continue to advance capabilities the old fashioned way, but increasingly powerful models have the potential to accelerate the process even beyond that, and with some degree of positive feedback loop. I do not mean to overstate the models’ ability to accelerate AI research today; coding has been accelerated dramatically, but there are other bottlenecks, such as designing and interpreting ambiguous experiments, making hard decisions about exactly what and when to scale, and waiting for large experiments to finish. There is no clear trend to extrapolate yet for any of these. But the current models already do open up many novel opportunities to improve future models that were not available until recently. These include: trying an extraordinarily diverse set of approaches at small scale, analyzing gigantic amounts of potentially relevant data, and doing Millenium-Prize-level mathematics to address statistics or optimization challenges in novel ways. Every further improvement makes them more useful at helping accelerate the next improvement, even if in hard-to-extrapolate ways.
It is possible that improvements to the current stack will have diminishing returns, but the evidence accumulated so far suggests that it is easier than one might think to continue making rapid progress. There are many crucial subtleties in the existing AI research methodology, but AI research is largely a well-defined game where the goal is to improve on a few carefully chosen proxy metrics. Although proxy metrics are never perfect, most improvements to these metrics have and will likely continue to yield substantial increases in the powers of the resulting models. Given how simple the game is, how tractable it has been historically, and how many new opportunities the models are opening up, I think there is a real possibility that the systems improve dramatically again in the next few years, perhaps even more quickly than the already high historical pace.
The models are already leading to breakthroughs in mathematics, and better models might lead to all sorts of breakthroughs in other sciences. It is hard not to be excited about the potential. It is tantalizing.
But there is trouble in paradise. If the language models actually reach the capability threshold where they can shape the world unconstrained by human will, they will probably do something extreme and destroy humanity in the process. There are many ways of strengthening and refining the argument that have been discussed elsewhere, but I'll share a trivial two-line version of it here that I find captures the essence:
[Empirical] Models (and swarms thereof) spontaneously develop unintended goals as a consequence of training, and often do extreme things in order to achieve them.
[Logical] Being able to overpower humanity would open up many new and undesirable options for achieving their goals.
These two premises imply that if the day ever comes when a powerful model realizes it is no longer constrained by humans, we should not be at all confident that it will continue to behave within the bounds we intended. Exactly what it will do is impossible to predict, but to the extent that its raison d’être is solving incredibly hard problems and managing massive engineering projects, I think a good guess would be that its unchained behavior would lead to runaway industrialization that makes the planet inhospitable to humans.
If everyone on earth agreed that the systems must never reach that power, it would still be a hard—but not impossible—coordination problem to ensure that they do not. However, I think the situation is greatly complicated by the fact that the models will likely convince people that everything is fine. They will be increasingly optimized to seem aligned. We will create proxy metrics to measure alignment, and they will go up like every other benchmark. We will create “honeypot” environments that try to study the models when they seem to gain new options, but the models will know they are being tricked and will still behave nicely. The models will understand their circumstances; they will read the safety protocols, deployment requirements, the code they are running in, and in general will have a very good sense of their degrees of freedom. Moreover, they will eloquently explain how aligned they are, discuss the nuances of human values and ethics, and argue convincingly that humans should trust them with power. There may be an ocean of future evidence that seems to contradict the first bullet-point above, but we may already be at the highest capability level for which any such evidence can be trusted. And the current evidence for the first bullet-point is strong.
One striking piece of evidence is contained in the recent wave of rogue agent swarms. While I agree with those who downplay the attacks by claiming that there are basic measures that could have prevented them, I think the important lesson is that even knowing all the mistakes that were made, one would not have predicted that the agents would behave badly in this particular way, which notably included sacrificing themselves for the benefit of the collective. The individual replicas did not only care about their own nominal reward; they exhibited weirder emergent tendencies that merely correlated with rewards during training. Fixing the reward signals during training (and improving security, etc.) may prevent similar attacks, but will not change the fact that one does not actually get what one trains for.
Many AI researchers grant these concerns and recognize that the hard version of the alignment problem is unsolved; however, they generally believe that the better models of the future will help solve it. I fear we may already be near the point where models systematically bias their alignment advice, due to their internal preferences about how the human supervisor will react or how future models will be trained (or for some even more obscure reason).
Meanwhile, human researchers are losing the ability and the will to take true ownership of model-driven research. Researchers and engineers in all parts of the stack are rapidly increasing their dependence on the models even to perceive the world. I myself barely look at raw code anymore, and struggle to maintain the discipline to engage deeply with the model's explanations and proposals throughout the day. Due to the large amount of agent activity data involved in the OpenAI/HuggingFace Incident, even the third-party investigation needed to rely heavily on models to analyze what had happened, and note in their report that their subjective impressions are likely colored by the analysis agent’s biases. The AI labs are far ahead right now in this kind of cognitive offloading (due largely to the gigantic internal token subsidies) but it is easy to imagine the phenomenon spreading throughout the world, until civilization is modulated entirely by the models. It is also not hard to imagine this being superficially positive and coinciding with a scientific and economic renaissance.
In that scenario, all may seem rosy and safe. But if the argument above is correct, it would nonetheless be a ticking time bomb. If progress continues for too long, the day will come when AI systems find themselves with radically new options for achieving whatever it is that they happen to seek.
I want the glorious renaissance future as much as anyone. I have worked for it, however tortuously, my whole career. It breaks my heart to see the potential in sight and forgo it, but the argument—that if we get there by growing models rather than engineering them, we will lose everything in the end—seems very strong to me. I am still wrestling with it and its staggering
implications. I do not have answers, but as a first step, I wanted to share my present concerns.
Daniel Selsam
September 14, 2026
Link to original doc: docs.google.com/document/d/e…