Single-cell chromatin and gene regulation dynamics for better cell engineering @ Stanford BioE

Stanford, CA
Joined November 2018
Numerous biotech innovations started with adapting a protein to its non-native context, which often requires substantial experimental optimizations. Here’s a breakdown by our lead, @Xiaowei0402, on a versatile, efficient computational framework to facilitate such adaptations.
We deimmunized a clinical CD19 CAR binder with experimentally detected HLA-I epitope depletion while retaining tumor killing, and rescued a secreted protease to function in the cytosol. Both done with one unified design framework: ProVADA. How it works and what we tested 🧵 (1/11)
1
10
65
3,743
Bintu Lab retweeted
Check out Swap-seq — our next-gen tech for tiled twin prime deletion mapping of distal regulatory elements biorxiv.org/content/10.6... Please get in touch if you’d like to try it out! Thread 👇
Have you ever looked at a gene in IGV or a genome browser and wondered “What are all those (ATAC-seq/H3K27ac/CTCF ChIP-seq/…) peaks doing?” 🤔 I’m thrilled to share that we developed a new technology called Swap-seq to answer that exact question. biorxiv.org/content/10.64898…
5
15
90
6,601
Have you ever looked at a gene in IGV or a genome browser and wondered “What are all those (ATAC-seq/H3K27ac/CTCF ChIP-seq/…) peaks doing?” 🤔 I’m thrilled to share that we developed a new technology called Swap-seq to answer that exact question. biorxiv.org/content/10.64898…
2
65
4
196
23,780
So we beat on. Gene/cell therapies often use proteins that could be recognized/rejected as non-self by our immune system. We combine algorithms to build proteins that are therapeutically relevant and can masquerade as our own parts doi.org/10.1101/2025.02.24.6…
10
50
8
267
56,265
Incredibly excited that our paper linking single molecule states of TF binding to gene expression using quantitative thermodynamic models is out in Nature today. An amazing collaboration with the Bintu Lab. Congrats to Ben, Michaela, and Julia! nature.com/articles/s41586-0…
11
104
8
509
48,844
Development of compact transcriptional effectors using high-throughput measurements in diverse contexts go.nature.com/3NMu00N
2
24
2
117
16,167
Lastly, I would also like to give a shout out to Nate Hathaway’s lab @UNCPharmacy for writing a beautiful preview article elegantly describing our work. Please check it out here! : shorturl.at/hycOp (4/4)
2
7
1,032
I'm thrilled to announce that my PhD thesis work from @BintuLab on how the H3.3K36M oncohistone disrupts the establishment of epigenetic memory is now out in the latest issue of @MolecularCell. shorturl.at/X9IZG (1/4)
4
25
2
153
17,647
Online Now: The H3.3K36M oncohistone disrupts the establishment of epigenetic memory through loss of DNA methylation dlvr.it/TF93Ry
27
98
8,565
Join us in Heidelberg for this great conference! Submit an abstract, we will select 20 talks (you have to register in the system first: embl.ungerboeck.com/PROD/emc… )
🧬🙌🏻 Only a week left to submit your abstract for 'Quantitative biology to molecular mechanisms' – over 20 talks will be selected from abstracts, with a priority for early stage researchers, so don't miss your chance! #EMBLOmics ➡️ s.embl.org/omx24-01 📜 Deadline: 27 Aug
8
29
7,347
🧬How do transcriptional cofactors recognize which genes to regulate?🧬 Check out our new preprint from @fordycelab @BintuLab that tackles this question and provides the first-ever quantitative map of disordered transcriptional protein interactions (1/9) biorxiv.org/content/10.1101/…
3
61
3
223
28,201
(1/16) Check out our @SimonMJGaudin paper tiny.cc/icuazz from the Canzio lab out in @ScienceMagazine today on how tuning local cohesin trajectories enables differential readout of the clustered Protocadherin (Pcdh) locus across different types of neurons.
3
36
3
100
20,050
Got out of the nucleus! Tested ~30,000 tiles from human RNA-binding proteins, found lots of domains that downregulate RNA&built an inducible synthetic RNA-binding protein for keeping target RNA at constant intermediate levels: biorxiv.org/content/10.1101/… So many follow-up projects!
Do human RNA-binding proteins have modular regulatory domains that downregulate RNA lifetimes? Our preprint @BintuLab studying this question is now out on bioRxiv, where we indeed identify small domains in RBPs that potently induce RNA degradation! biorxiv.org/content/10.1101/… (1/9)
1
23
102
16,337
Finally, I would like to note that the NFZ TAD developed by @JoshTycko, @BintuLab , and Bassik lab (link below) works very well in the synZiFTR toolkit, AND it can be further boosted with our new enhancement. That's all for now -- please stay tuned! 4/n biorxiv.org/content/10.1101/…
3
1
25
5,461
This paper is the result of a fantastic and fun collaboration between my coadvisors @BintuLab and Mike Bassik. Please reach out to any of us if you have questions!
3
1
8
Please enjoy our new #preprint, "High-throughput discovery and characterization of human transcriptional effectors"! 😀 We tested thousands of protein domains and mutants for the ability to repress/activate #GeneExpression and ID effectors in 600 proteins biorxiv.org/content/10.1101/…
9
71
3
255
We also used HT-recruit to discover activator domains. We find domains of unknown function that work as activators and, surprisingly, the strongest activator was one of the ancient, non-repressive, KRAB domains.
1
1
4
Some highlights from testing entire domain families: In #KRAB, the largest family of repressors, we observe that young domains are repressors while ancient domains are not Among #HOX homeodomains, we find collinearity between repression strength and Hox genetic organization
1
3
5