I am so excited to share our new paper in @Nature: the first programmable, site-specific integration of a large DNA payload into T cells in vivo. A single IV injection results in therapeutic levels of TRAC-targeted CAR T cells in multiple models. nature.com/articles/s41586-0… a 🧵

Proud supporters of this at @open_phil after we saw @mfgrp’s wild paper on it a few years ago. Much left to figure out! Chasing down “big-if-true” findings like this is a good fit for science philanthropy, since donors can move quickly, flexibly, reactively vs govt grant cycles

Saw a talk this week on the trippiest thing: bacterial cultures on skin induce immune responses. At Michael Fischbach's lab, they demonstrated immunizing mice against tetanus by just dabbing an engineered version of a harmless staph culture on its head. Unlike intramuscular vaccination, the antibody levels don't seem to demonstrate any waning, even after a year. This is both scientifically very interesting (can vaccines just be... creams?), and an amazing reminder of how much we still don't know. We could have discovered this decades ago, but somehow never noticed until now.

The Weill Cancer Hub is fostering groundbreaking @UCSF–@Stanford collaborations to develop transformative cancer therapies. I’m grateful to co-lead one of the selected teams with @mfgrp to advance next-generation in vivo CAR T cell therapy!

I’ve been busy this week… 👀 Passed my PhD defense! Insanely grateful for @mfgrp. Truly epic scientist and human.

What an amazing story that was such a blast to collaborate on with @mfgrp lab!!! Phenomenal work led by @DjenetBousbaine and all co-authors!! Unroll this thread and be amazed 🤯👇🏾

A typical project for an incoming graduate student might involve 1–2 weeks of planning and 2–5 years of execution, [yet] the problem you choose will influence the impact of your work just as much as the quality of your execution. – Michael Fischbach buzzsprout.com/1744020/episo… @mfgrp

@SU2C Scientific Advisory Committee member @mfgrp published a paper in @Nature showing that immunity to a common skin bacteria involves a coordinated T and B cell response, which can be redirected against pathogens as a novel form of topical vaccination nature.com/articles/s41586-0…

Extremely proud to find this innovative vaccine platform from Michael Fischbach at Stanford. Imagine no more jabs! Low cost and globally deployable. thetimes.com/uk/science/arti…

The skin — once thought to be a mainly passive barrier — can produce its own antibodies that fight off infections nature.com/articles/d41586-0…

take some time now to read this thread it explains what happens with the immune system when swabbing (no entry!) a bacteria on the head of a mouse it beautifully walks us through the years-long scientific journey and is exemplifies how our competitors are in fact our friends❤️

imo this is one of the most exciting lines of immunology research in recent years

wow 😮 🦠

Big leap forward in our understanding of interactions between our immune systems and microbiomes, and a promising path to new and better vaccines

👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀 And did I say 👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀👀

Epic thread. Not just a very promising result, but also a good story of how research is done.

Could one envision a synthetic receptor technology that is fully programmable, able to detect diverse extracellular antigens – both soluble and cell-attached – and convert that recognition into a wide range of intracellular responses, from transgene expression and real-time fluorescence to modulation of innate cell behavior (excitation or inhibition of neurons, induction of cell migration, etc.)? Today we report in Nature a new technology platform that provides a step in that direction: PAGERs, for Programmable Antigen-gated G protein-coupled Engineered Receptors, convert recognition of extracellular soluble or cell-attached antigens into diverse user-selected responses. PAGERs are based on G-protein coupled receptors (GPCRs), which themselves are not structurally modular, but we were able to build in modular antigen gating by fusing an antagonist peptide to the extracellular N-terminal end, and then gating the antagonist with a fused antigen-binding nanobody.  When antigen binds, it sterically interferes with the antagonist, leading to relief of receptor inhibition. Drug or agonist can then turn on PAGER. nature.com/articles/s41586-0…