Assistant Professor @ Stanford ChemE synthetic biology, biomolecular engineering synbiogaolab.bsky.social/
Stanford, CA
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Editing 14 genes is no small feat, but I am not seeing enough evidence that "it is a dire wolf". Our community needs to communicate better to the public, now mor than ever, and imo that includes not exaggerating what we can deliver.
TIME's new cover: The dire wolf is back after over 10,000 years. Here's what that means for other extinct species ti.me/4jlJB54
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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…
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Our ADAR-based RNA sensors just came online! rdcu.be/cWX7o It allows you to express protein payloads in live cells in direct response to the presence of specific RNA transcripts. Also @EerikKaseniit, welcome to twitter.
As we work towards DNA-free circuits, we realized we could use some new RNA sensors in living cells. So we built RADAR biorxiv.org/content/10.1101/… Congrats to Eerik, @katznoa1, @NatalieSKolber, @claytoncalli, and thanks to our plant biologist neighbors, Diego, Will, and @Sattely_lab
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As we work towards DNA-free circuits, we realized we could use some new RNA sensors in living cells. So we built RADAR biorxiv.org/content/10.1101/… Congrats to Eerik, @katznoa1, @NatalieSKolber, @claytoncalli, and thanks to our plant biologist neighbors, Diego, Will, and @Sattely_lab
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Excited to announce the opening of my lab in Stanford ChemE next April! Tinkering with molecular circuits, viral vectors, and human cells for new biomedical solutions. Partners in crime wanted: students, postdocs, collaborators… More at gaolab.blog
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Save the date: the 10th (!) Mammalian Synthetic Biology Workshop will be held on 6/22-6/23, 2023 at Stanford. For the very first time on the west coast of the US.
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Radar Tx is de-stealthed today! It's been so great working (or rather, tagging along) with co-founders, @EerikKaseniit, Sophia Lugo, and Jim Collins. We've assembled a stellar research team, forging ahead with new designs. We are still hiring more. endpts.com/startup-launches-…
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Following our field's inspiring history of building synthetic receptors, here we share our lab's first attempt at a post-transcriptional one. Based on ADAR-editing and compatible with various inputs/outputs.
Post-Transcriptional Modular Synthetic Receptors
ift.tt/Yu9qIdk
#biorxiv_synbio
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When we talk about viral protease-based circuits, people wonder: "if it's meant as therapeutics, are you concerned about immunogenicity"? Now, in hDIRECT, we established control of cytokines using a human protease and its FDA-approved inhibitor: doi.org/10.1101/2024.01.18.5…
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LIDAR is out! rdcu.be/efugD We've improved a lot, e.g., making MESA-like LIDAR work, RNAseq of on-/off-target editing, and optimizing RNA delivery. We are one baby step closer to making it useful for therapeutics. NIH high-risk high-reward program provides key support.
Following our field's inspiring history of building synthetic receptors, here we share our lab's first attempt at a post-transcriptional one. Based on ADAR-editing and compatible with various inputs/outputs.
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This is now officially the first peer reviewed paper from our lab :) rdcu.be/cHcAc Did I mention that we are always looking for synbio-curious students and postdocs to develop/apply RELEASE, RADAR, and more tools down the pike?
Wish you could control intercellular communication using protein circuits? First preprint from the lab! Proud of what @AlexVlahos, Jenny, and Carlos achieved, and how every lab member persisted through COVID. Also missing old colleagues @RonZhu2015, Lucy, and @ElowitzLab already.
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Wish you could control intercellular communication using protein circuits? First preprint from the lab! Proud of what @AlexVlahos, Jenny, and Carlos achieved, and how every lab member persisted through COVID. Also missing old colleagues @RonZhu2015, Lucy, and @ElowitzLab already.
Excited to share the first work from my post-doc with @SynBioGaoLab at @Stanford_ChEMH. This pre-print highlights a platform to control the secretion and display of proteins that is compatible with pre-existing protein based synthetic circuits.
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And thank you, @GrinsteinJ for the nice interview with Eerik and Josh: Programmable RNA Sensors Enable Cell Editing and Therapeutic Intervention genengnews.com/gen-edge/prog… via @GENbio
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It's published! rdcu.be/d6kVt
When we talk about viral protease-based circuits, people wonder: "if it's meant as therapeutics, are you concerned about immunogenicity"? Now, in hDIRECT, we established control of cytokines using a human protease and its FDA-approved inhibitor: doi.org/10.1101/2024.01.18.5…
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Pls RT: Do you wanna meet synbio friends old and new? Do you always wonder what mammalian synbio is about? Do you just need an excuse to visit San Jose in summer? The 10th mSBW is open for registration mammalian-synbio.org/2023! Abstract deadline coming up soon too.
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Grateful for the recognition and for my team's dedication. When I wrote it in Oct, I didn't anticipate that the title would feel defiant. The original draft even had a now quaint reference to "the comparative comfort of the ivory tower", which was wisely removed.
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So great meeting everyone again at #msbw2022! Here's Eerik sharing RADAR and reminiscing on the first mSBW :)
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I don't usually tweet grant outcomes for various reasons, but the experience of applying to this one was so refreshing! Thanks to @MartinBJensen and the Impetus Grants and congrats to the other grantees. Looking forward to developing synbio for precision senolytics.
This week we have several new winners to announce, doing either tool-building or testing out-of-the-box ideas:
🪙 @SynBioGaoLab, @Stanford
🪙 @ScheibyeKnudsen, @uni_copenhagen
🪙 @labmccormick, @UNM
🪙 Alan Cohen, USherbrooke
Congratulations all!
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Building on our RELEASE and @rjerala's lumER/membER, we (@AlexVlahos @claytoncalli and the amazing undergrads Sam and Siqi) made a much more compact platform for protein-level regulation of intercellular communication. biorxiv.org/content/10.1101/…
This is now officially the first peer reviewed paper from our lab :) rdcu.be/cHcAc Did I mention that we are always looking for synbio-curious students and postdocs to develop/apply RELEASE, RADAR, and more tools down the pike?
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Directed evolution at its finest. Altering TEV protease specificity. biorxiv.org/content/10.1101/… Congrats! @CarlDenard
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Synbio loves IFFLs, including recent cool works from @ElowitzLab and @GallowayLabMIT. We implemented protease-based IFFLs with unique features for dosage control, and demonstrated them against Rai1 that underlies conditions like SMS and PTLS doi.org/10.1101/2024.10.09.6…
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It'll be bittersweet to see you leave. Thank you for all your contributions. Can't wait to see what a kind lab you'll build and amazing engineering you'll lead, Alex!
I am excited to share that I will be starting as a tenure track Assistant Professor in @CoulterBME at @GeorgiaTech in the upcoming year. I am very grateful of the unwavering support of my postdoctoral mentor, @SynBioGaoLab , and my PhD supervisor, Michael Sefton.
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I forgot to mention that Eric, the grad student who leads this, is considering his next steps. If you wanna steal someone who (almost single-handedly) pulled off this interdisciplinary work for your company/lab, please DM me and I can put in a good word for you :)
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…
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We requested a few that we couldn't synthesize otherwise, and got them through this very first shipment. Cloning went smoothly and the sequences look perfect. Thanks to @AnsaBio for the enabling tech and Early Access!
Announcing 2 key milestones today:
1️⃣ We have synthesized and delivered complex clonal DNA sequences to multiple customers participating in our Early Access Program.
👇
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$100 to register. Our proud tradition of affordability for mammalian synthetic biology workshop. Only two days left to take advantage of it though. mammalian-synbio.org/2023 I can't wait to check out all the outstanding talks and posters that we could barely fit into two days.
We (@genegirl007
@MoKhalilLab
@RogelioHdezL
@LeonardoMorsut
@VeliaSiciliano
@BintuLacra
@GallowayLabMIT
@TheLeonardLab @RosserLab @Ron_Weiss_MIT @diegodidibi and Wilson Wong) have been trying our best to put together a program that you might just enjoy.
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Btw, Alex happens to be the first postdoc to join (and to move on from) my lab. He certainly knows what it's like to grow together with a new lab. To the grad students out there considering postdoc labs: I'm sure he's now well prepared to grow with you.
Our lab will focus on synergizing mammalian synthetic biology with tissue engineering for biomedicine, focusing on improving cell therapies for regenerative medicine or treating cancer. Please spread the word - we are hiring at all levels! #tissueengineering #synbio #diabetes
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mSBW back in Boston next year!
Mark your calendar for the 2024 International Mammalian Synthetic Biology Workshop - uniquely focused on mammalian cell engineering & rational design approaches, pushing the field beyond transgenics & gene editing. Abstracts open soon - bit.ly/48hTZVN
#SBE #mSBW2024
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A state senate bill that will ban citizens of China, Iran, North Korea, or Russia from purchasing real estate. You don't need to be a historian to see where it's going.
No to the bill: chng.it/LGL6cDHm via @Change
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It went by too fast.
Thank you everyone who came to #msbw2023 to share your work! This is (most) of the organizing committee who made it possible. See you next year! 💕
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If you started your weekend agonizing over missing the mSBW abstract deadline, don't! We've extended it to the next weekend. We've got quite some exciting submissions but would always love to hear more from our community. mammalian-synbio.org/2023
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Yes, you hear John right: we brought the already low student registration fee further DOWN.
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Thank you for being such a leader and role model, @CarolynBertozzi! Apparently Stanford decides to inspire us more by juxtaposing our paper with your lecture 😅 @Stanford_ChEMH
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Curious about synbio + tissue engineering (and much more)? Check out Alex's poster and talks at AICHE!
Excited to be at @ChEnected annual meeting this week! Catch me at the MTFC poster session tomorrow 1-3pm (poster 335) and in Monday's Faculty candidate oral session (1:42 pm in Celebration 15). Excited to share my vision on using synthetic biology to create smart therapeutics!
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Cool new RNA/DNA sensor combining RT and splint ligation!
1. Happy to share our latest work @biorxivpreprint on developing SONAR (Sensing Of Nucleic acids using ASOs and Reverse-transcriptases) for sensing and responding to nucleic acids in living cells.
biorxiv.org/content/10.1101/…
👇🧵
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Thank you, Darren Burgess, for the nice highlight of our work @NatureRevGenet! nature.com/articles/s41576-0…
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Don't forget to check out the impressive work from @omarabudayyeh @jgooten @insitubiology biorxiv.org/content/10.1101/… Apparently we didn't save enough creativity for diversifying the acronyms 😅
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A cool RNA sensing mechanism! nature.com/articles/s41467-0…
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Apparently the doi link isn't working yet. Here's the BioRxiv: biorxiv.org/content/10.1101/…
Synbio loves IFFLs, including recent cool works from @ElowitzLab and @GallowayLabMIT. We implemented protease-based IFFLs with unique features for dosage control, and demonstrated them against Rai1 that underlies conditions like SMS and PTLS doi.org/10.1101/2024.10.09.6…
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Also check out lumER and membER from the great @rjerala lab! It's fun to compare our design decisions. When we realized we were working on these strategies in parallel, we decided to preprint together. biorxiv.org/content/10.1101/…
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Wish I could be there. Folks, check out Alex's poster on protein-controlled intercellular communication: Poster # 641324 at the Wednesday afternoon session!
Excited to be representing @SynBioGaoLab at #seed2022! First conference since the pandemic and excited to connect and learn about some cool work being done in the field!
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Personally vouch +1
Stanford Chemical Engineering is hiring!! I have amazing colleagues and will personally vouch for our department as incredibly supportive of junior faculty members. Applications due Nov. 1, more info here:
facultypositions.stanford.ed… @StanfordEng
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We (@genegirl007
@MoKhalilLab
@RogelioHdezL
@LeonardoMorsut
@VeliaSiciliano
@BintuLacra
@GallowayLabMIT
@TheLeonardLab @RosserLab @Ron_Weiss_MIT @diegodidibi and Wilson Wong) have been trying our best to put together a program that you might just enjoy.
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We (@genegirl007 @MoKhalilLab @RogelioHdezL @LeonardoMorsut @VeliaSiciliano @BintuLacra @GallowayLabMIT @TheLeonardLab Ron Weiss, Susan Rosser, Wilson Wong, and Diego Di Bernado) look forward to seeing everybody here!
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Online at the same time is CellREADR! rdcu.be/cWX7m
And now more ADAR-based sensors from Josh Huang's lab at Duke by Yongjun Qian et al. They took it all the way to the human cortex! biorxiv.org/content/10.1101/…
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And now more ADAR-based sensors from Josh Huang's lab at Duke by Yongjun Qian et al. They took it all the way to the human cortex! biorxiv.org/content/10.1101/…
As we work towards DNA-free circuits, we realized we could use some new RNA sensors in living cells. So we built RADAR biorxiv.org/content/10.1101/… Congrats to Eerik, @katznoa1, @NatalieSKolber, @claytoncalli, and thanks to our plant biologist neighbors, Diego, Will, and @Sattely_lab
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We've been using NFZ. As great as advertised!
New preprint! 🗞️ We used pooled protein screens to develop compact human transcriptional effectors that work across diverse biological contexts to activate or silence gene expression
biorxiv.org/content/10.1101/…
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This work was led by an amazing grad student @carlosaaldrete1, with contributions from @AlexVlahos and our collaborators, Jimin and Qian, who provided critical insights on engineering orthogonality.
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Congrats to co-leads, @Xiaowei0402 & @santimillef , as well as @EerikKaseniit, @claytoncalli, @mengzhang668, @FloraHU8, and Yunxin!
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It's exciting to see proteases' new adventures with ELPs. Congrats, Brendan, Danielle, and all the other co-authors!
Our report on protease-responsive elastin-like polypeptides (ELPs) is now published in Biomacromolecules @MacroJrnls_ACS! PhD student Brendan (@bmwirtz00) explored how proteases can drive phase separation of ELPs. pubs.acs.org/doi/10.1021/acs… Learn more from his tweetorial: 🧵 (1/n)
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Thank you for organizing this, Tae Seok!
#SynBYSS with Dr. David Rampulla, an @NIH director & Prof. Xiaojing Gao @SynBioGaoLab at @Stanford
piped.video/mhWrR2gakH8 via @YouTube
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If I might clumsily point out the economic impact: our project germinated from @impetusgrants and an NIH trailblazer grant that add up to ~$0.5M, and now our company supports a dozen employees.
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If you wonder about the exciting directions @AlexVlahos's taking RELEASE/compRELEASE in, ask him at the meet-the-faculty poster sessions at BMES and AICHE!
Building on our RELEASE and @rjerala's lumER/membER, we (@AlexVlahos @claytoncalli and the amazing undergrads Sam and Siqi) made a much more compact platform for protein-level regulation of intercellular communication. biorxiv.org/content/10.1101/…
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We were inspired by pioneering humanization works from @KoleRoybal and @chembioBryan labs. We especially stood on the shoulders of @MoKhalilLab
lab's synZiFTRs.
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mSBW abstract deadline soon!
Collaborate in mammalian synbio #research to leverage diverse expertise, resources, and perspectives. Advance scientific knowledge & drive innovation in biomedicine & beyond. Help shape the future of this field! Abstracts end April 16 - bit.ly/49qbofF
#SBE #mSBW2024
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SynNotch (and other cool stuff) comes to Stanford! Looking forward, Rogelio!
🟢 My lab is opening in May! 🎊I am #recruiting at all levels to build a diverse group. Join us in discovering new biology and engineering next-gen biotechnology! #synbio #immunology #cancer #microbes Please reach out and RT to help me spread the word! 👉 hl-lab.org/
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Make sure you check out the stunning videos!
Very excited to share our new preprint where we use a deep learning-based feedback algorithm to control gene expression in real time in thousands of single E. coli cells in parallel. This work was led by @jblugagne and @cblassick. 1/
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Higher-order infinitesimal in light of the challenges we are all going through, but still happy that the preprint is out. Missing @ElowitzLab already. Kudos to Michaela and Matthew. Can't have found a more perfect collaborator than Lucy. Thank you all!
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Hard to say since I haven't read the paper from Colossal yet. Based on this though doi.org/10.1038/s41586-020-0…, I suspect it is still more wolf than dire wolf after the claimed number of edits.
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It will be presented by Connor @cnnrcall who's been co-leading the project!
A platform that allows protein secretion systems to achieve the same tuning capabilities seen in gene circuits? @SynBioGaoLab has created just the thing & it's made possible w/ enzymatic #DNAsynthesis by Ansa.
🗓️ Learn more at our free Dec 10 webinar: fiercebiotech.com/premium/we…
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Led by Eric, with key contributions from JS, and featuring MHC presentation prediction from @DrBinSquared in @AshAlizadeh lab and humanized transcription activation domain from @JoshTycko in @BintuLab and @MCBassik labs.
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Sorry I missed Diego's handle too @diegodidibi and misspelled his name... I'm really bad at this :(
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CMVTO-SEAP-26Sfur-3TM-hcvs-KKMP (GS)
Depositor: @SynBioGaoLab
Purpose: HCVP-inducible tri-transmembrane SEAP RELEASE with GS linkers
hubs.la/Q01jX9nL0
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Mammalian Synthetic Biology Workshop goes to the UK!
It's official! The next Mammalian Synthetic Biology Workshop will be IN PERSON in Edinburgh! Stay tuned for updates! @RosserLab @MoKhalilLab @LeonardoMorsut @TheLeonardLab @Ron_Weiss_MIT @VeliaSiciliano @Laura_RiceU @SynBioGaoLab @GallowayLabMIT @BintuLacra @drkahaynes #msbw2022
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More importantly, for diseases that have to be addressed using nucleic acid therapies, such as some recalcitrant cancers, RNA offers the safer option than the more conventional DNA vectors, because RNA is less likely to leave permanent marks in the patients' cells.
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Congrats again to everyone, especially @carlosaaldrete1 , and @cnnrcall for the functional an in vivo additions during revision.
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Thanks, Lada! One outcome of duct taping the algorithms together is that we realized we can program human zinc fingers with a reasonable success rate (3 out of 3 so far for on-target activation), if that's of any use to anyone.
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We are grateful for Impetus's support when the tech was at a very early stage, Lada! Can't wait to see where we can take it from here.
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None of it would've been possible without the support of NIH and private foundations. We view this as an important step towards helping more patients, such as those with Duchenne muscular dystrophy or Dravet syndrome, with future gene and cell therapies.
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As is typical of such works, we built on what came before us, esp. the ZF programming model developed by
@hsnajafabadi et al, and the protein language model-guided optimization demonstrated by @BrianHie
et al and others.
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It's probably a typo, but chances are the the pups are 99.999999...% gray wolf genome-wise :) how many 9s depends on what the edits are.
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But we wouldn't point to that child and say it's a resurrected Michael Jordan, would we? Even though the difference between the child and Jordan would be much smaller than that between "dire wolf" and dire wolf.
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Haha, I've been mildly annoyed by hypes since forever, but used to "have better things to do".
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Apparently the original post was gone. Here's what the post is referring to: doi.org/10.1126/science.adw0…
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I see our key contribution as demonstrating the simultaneous deployment of multiple algorithms. Immunity-wise, right now it's only based on predicted HLA presentation. It's probably possible to plug in another filter for tertiary epitopes, if there's a good algorithm.
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This works is co-led by @katznoa1 and connie, in collaboration with Wei-Hsiang Huang's lab at McGill, and featuring contributions from Yu-Ju, @JoshTycko, @mengzhang668, Jenny, @BintuLacra, and @MCBassik
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Looking forward to all the great talks! Also check out the NSF funding opportunity, great for trainees who are curious about synthetic biology.
The deadline is approaching to submit an abstract for the Mammalian Synthetic Biology Workshop (June 27)! See comments for opportunity for free registration. #msbw2021 mammalian-synbio.org/2021
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Also precisely to your very nicely argued point, our brains are almost wired to see and believe dire wolves, that makes it all the more important for the communicator to not abuse that. That's why I was upset enough to say anything. Thank you for the engaging discussion.
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If the goal is to resurrect a species, using the definition of species that most of us think of, I don't think one can get there with the current editing tools we have.
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Yeah, I've compared something like TVMVP-2A-TEVP vs TVMVP-tevs-TEVP. They showed different apparent stoichometry... Didn't bother to look deeper into that but I suspect either the protease cleavage efficiency isn't close to 1 or the scars affect activity.
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