Alexander Stark

@garrytan It's always nice to see more people in this space, but "barely touched territory" seems exaggerated. To design these enhancers, they use a model from a paper that also does AI-based enhancer design! And they provided wetlab validation of their sequences.

The Programmable Genomics Lab at @UMassGCB just officially launched our site! We have a "simple" goal: to develop synthetic regulatory elements that target every cell type in every tissue, and control payload dosage/duration Check it out! programmable-genomics.github.io

The way to accelerate science is to SLOW it down. Fewer papers please! We’re drowning in meaningless text. One GREAT paper per lab per decade is more than enough. q.e.d 👇

@OdedRechavi I would NOT want q.e.d. be my reviewer

@OdedRechavi in my experience q.e.d. provides interesting feedback but is essentially useless without expert interpretation. it comes up with all kinds of nitty gritty stuff

AlphaGenome is out in @nature today along with model weights! 🧬 📄 Paper: nature.com/articles/s4158… 💻 Weights: github.com/google-deepmin… Getting here wasn’t a straight path. We sat down @googledeepmind to discuss the story behind the model, paper & API: youtu.be/V8lhUqKqzUc

@fiddle @MoffittLab @CSHL Deadline TODAY January 23 - please join the Systems Biology: Global Regulation of Gene Expression meeting in beautiful @CSHL (March 11-14). Register and submit your abstract here: meetings.cshl.edu/meetings.aspx?…. Please Repost!

@fiddle @MoffittLab Deadline extended to January 23 - please join the Systems Biology: Global Regulation of Gene Expression meeting in beautiful @CSHL (March 11-14). Register and submit your abstract here: meetings.cshl.edu/meetings.aspx?…. Please Repost!

Join @fiddle, @MoffittLab, @sara_mostafav, me and all speakers for the 2026 CSHL meeting Systems Biology: Global Regulation of Gene Expression, March 11-14. Abstract deadline January 9! More infos and registration at meetings.cshl.edu/meetings.aspx?…

Our preprint "Predictive design of tissue-specific mammalian enhancers that function in vivo in the mouse embryo" is on bioRxiv: biorxiv.org/content/10.648… . Amazing collaboration by @TedChen1999CN, @Loubiere20 (@IMPvienna, @viennabiocenter), ... (1/2)

Now on bioRxiv: Activator-promoter compatibility in mammals - Hcfc1 is a key and intrinsically CGI-promoter-specific co-activator that cannot activate non-CGI promoters. Lead by @FilipNemcko & Kevin Sabath in collab. with @plaschka_lab (@IMPvienna) biorxiv.org/content/10.648… (1/2)

Read the full story in our preprint! 👇 biorxiv.org/content/10.648… Excited to share this work with my co-first author Kevin Sabath - a fantastic collaboration between the @AlexanderStark8 and @plaschka_lab labs! 🤝🧪

Using Hcfc1 as a model, we show it functions as a molecular bridge: it connects CGI-bound TFs directly to TFIID. This recruitment overcomes a rate-limiting step unique to CGI promoters, enabling transcription initiation. 🧬🌉

Do transcriptional activators work on any promoter? Our data says no. 🙅‍♂️ Despite driving ~2/3 of mammalian genes, CpG island (CGI) promoters have remained a puzzle. We identified >50 activators that are exclusively compatible with this promoter class. 🧬

I have always been fascinated by transcriptional activators that display intrinsic specificity towards some but not other promoter types as these imply alternative mechanisms! Hcfc1 directly bridges TFs to TFIID to overcome a rate-limiting step and activate CGI transcription.

... @jmschreiber91 (now @UMassChan), @evgenykvon (@UCIBioSci,@UCIrvine), and all other authors! Congrats to the entire team, you're making dreams come true - de novo enhancer design in mammals, in vivo! Happy holiday reading to all: biorxiv.org/content/10.648… .