Mike Lee

New music alert!! In my pre-science life I used to make music 🎸🎤🎵 And I just put out a new song! The link below will get you to your preferred streaming/music service. Check it out 🙂 onlyonce.hearnow.com

@stolinski It’s crazy how may replies here missed your point entirely 🤦‍♂️

It's crazy how AI is really good at the stuff I don't know anything about and total dog shit at the stuff I do.

The archaeal roots of eukaryotic life pnas.org/doi/10.1073/pn… 🧬💻🧪

Sassy2: Batch Searching of Short DNA Patterns biorxiv.org/content/10.648… 🧬💻🧪 github.com/RagnarGrootKoe…

Accelerating minimap2 for whole-genome alignment academic.oup.com/bioinformatics… 🧬💻🧪 github.com/at-cg/mm2-plus

A new mechanism for “RNA memory”! 😱 Thrilled to share another crazy paper from the lab (can’t believe we posted 2 in 2 days!), summarizing >10 years of research: Work on transgenerational inheritance of small RNAs in the powerful model organism C. elegans changed how we think about what’s possible in inheritance and evolution, because it allows the most heretical thing: inheritance of parental responses to the environment! However, it’s still unclear whether RNAs are inherited across generations in other animals, largely because the RNA-dependent RNA polymerases that amplify heritable small RNAs and prevent their dilution in C. elegans are not conserved in mammals. In this new work, an amazing collaboration with the Rink and Wurtzel labs, we show that planarians establish long-lasting and heritable small RNA–based gene regulatory states despite lacking canonical RNA-dependent RNA polymerases and nuclear RNAi machinery (that are required in C. elegans). You might say “they are both worms…” BUT planarians are evolutionarily very distant from C. elegans (flatworms vs. roundworms, diverged more than 500 million years ago), making this particularly surprising. These are totally different animals. We find that ingestion of double-stranded RNA induces sequence-specific silencing that persists for months and survives repeated cycles of whole-body regeneration. Even more strikingly, RNAi can be transferred between animals, echoing James V. McConnell’s controversial “RNA memory” experiments from the 1970s (his lab was targeted by the Unabomber terrorist Ted Kaczynski, who sent McConnell a bomb. This and other controversies ended this line of experiments…) Mechanistically, we find that the response transitions from a transient systemic dsRNA-triggered phase to a stable, cell-autonomous post-transcriptional “memory phase” maintained by antisense small RNAs. Using a new luminescence reporter (transgenesis is currently impossible in planarians), we show that silencing spreads along the targeted gene and identify a weird type of planarian small RNAs with untemplated polyA tails. RNAi inheritance without canonical RdRPs establishes planarians as a powerful system for studying RNA-based regulatory inheritance beyond C. elegans and raises the possibility that RNA-mediated inheritance may be more broadly conserved in animals, potentially even in mammals. Here’s a video of a planarian that is treated by RNAi against β-catenin and develops multiple heads instead of just one. This is one of the phenotypes that is inherited. Another phenotype is “loss of eyes” (which we show is not only inherited across multiple regeneration cycles, but can also be transmitted between animals in transplantation experiments). Amazing work led by first authors Prakash Cherian and Idit Aviram (co-supervised by Omri and me). Please read the preprint, the link is in the next tweet, and share!

geneSTRUCTURE: A Modern Platform for Visualization of Gene Structures biorxiv.org/content/10.648… 🧬💻🧪 github.com/hashimotoshump…

Big update for #gbdraw! - Multi-record circular plots: Genomes with multiple replicons can now be displayed in a single view! - Advanced linear plots: Focus on regions of interest with granular control over feature selection and color-coding! Try now: gbdraw.app

Excited to share this preprint that describes my latest work on using GPUs to accelerate processing of RNA-seq data. The title says it all: "RNA-seq analysis in seconds using GPUs" now on biorxiv biorxiv.org/content/10.648… Figure 1 shows they key result

I used Claude Opus 4.5/4.6 (and a bit of Codex GPT-5.3) to port edgeR to Python. See edgePython github.com/pachterlab/edg… This allowed me to develop a single-cell DE method that extends NEBULA with edgeR Empirical Bayes. All in one week. Details in doi.org/10.64898/2026.…

23 million people saw me say I was voting Trump I was wrong Now I want 23 million people to see this 🧵 ⬇️

Pleased to share this free link to our new review of genome annotation in @NatureRevGenet, which just appeared today. Co-authored with Hyunjoo (Hayden) Ji and Mihaela Pertea @elapertea. We focus particularly on human annotation: rdcu.be/e4mI1

mRNA: what happened — a COVID vaccine designed in an hour & delivered in months what’s coming — personalized cancer vaccines what’s now — a politician at FDA overruling career scientists to cancel the progress

“The vaccine doesn’t prevent COVID.” Neither does a seatbelt prevent car crashes. It prevents you from dying in one. The COVID vaccines were never sold as magical force fields. They were designed to train the immune system to blunt severity. And they did — dramatically. I wish they were a magic shield but they were not When vaccination rates rose, hospitalization and death rates fell — even as cases surged with new variants. If the vaccines “did nothing,” the ICU curves would have moved in parallel between vaccinated and unvaccinated populations. They didn’t. Protection against infection waned as the virus mutated. That’s virology. Coronaviruses evolve. So do influenza viruses. That is not scandal; that is biology. Esp RNA virus biology But protection against severe disease held far better — and that is what determines whether hospitals overflow and morgues deploy refrigeration trucks. The absolutist framing — “it doesn’t prevent COVID” — is rhetorical sleight of hand. It confuses “not perfect” with “not effective.” Nothing in medicine is perfect. The question is not whether breakthrough infections occur. The question is whether you are less likely to end up intubated, hypoxic, or dead. The data answered that clearly. You may resent mandates. You may dislike pharmaceutical companies. But epidemiologic curves do not care about resentment. They care about outcomes. And the outcomes shifted.

You are clinging to a statistic you don’t understand. The “6% died of COVID only” line comes from a CDC table listing death certificates that had no additional conditions recorded. That doesn’t mean the other 94% “didn’t die of COVID.” It means COVID caused pneumonia, ARDS, clotting, stroke, or heart failure — which is what viral infections do. When HIV patients died of pneumocystis pneumonia, we did not say, “Ah, they didn’t die of HIV.” We understood cause and consequence. Over 1.3 million excess deaths occurred in the United States during the pandemic period. That is not a rounding error. That is not “just flu.” That is a historic mortality event confirmed by excess death curves — which do not care about hospital coding, politics, or your favorite podcast. As for the claim that doctors diagnosed COVID for money — that requires believing that thousands of physicians, hospitals, coders, auditors, and insurers across every political jurisdiction engaged in coordinated fraud without evidence. That is conspiracy thinking dressed up as fiscal concern. And yes, early treatment evolved. That’s called science confronting a novel pathogen. If your standard is “medicine must be omniscient on day one,” then you are not arguing medicine — you are arguing for clairvoyance. The hospitals were full. The ICUs were full. Temporary morgues were deployed. Excess mortality surged in waves that matched viral spread across continents. You may dislike public health decisions. You may resent mandates. But denying the scale of mortality requires denying measurable reality. And measurable reality does not bend to ideology.

A major work from our lab is out in Science! @ScienceMag, another key step towards a true demonstration of RNA self-replication. science.org/doi/10.1126/sc… (1/6)

AI is cool and all... but a new paper in @ScienceMagazine kind of figured out the origin of life? The paper reports the discovery of a simple 45-nucleotide RNA molecule that can perfectly copy itself.

Introducing The Structural History of Eukarya (SHE): The first proteome-scale phylogeny constructed entirely from 3D structure. We computed 300 trillion alignments across 1,542 species to map the tree of life. 🧵👇 (1/5)

Scikit-bio: a fundamental Python library for biological omic data analysis nature.com/articles/s4159…

NASA internships I was fortunate enough to get when I was an undergrad motivated and enabled me to change my life ❤️

13 summer internships open at @NASAAmes in space life sciences, multi-omics, AI, biosensors, biomedical AI-Agent, ➕more. U.S. citizens | Undergrad juniors/seniors & grad students | Deadline Feb 27 @JasonWilliamsNY @mason_lab @SpaceAbhi @dr_alphalyrae @mkoeris @rookisaacman @phylogenomics @ThePrimalDino @RobMayeda @PracheeAC @SpaceKoala @BellikOzan @chrismattmann @mouthofmorrison @amir_deylami 🔗 awg.osdr.space/t/2026-nasa-am…