MD-PhD student @Harvard @MIT | interested in all things immuno, chem bio, viruses, IM, heme/onc, art hist | @Yale '16, NY native | @runthelistpod
Boston, MA
Joined September 2019
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Blake Smith retweeted
It’s hard not to get addicted to this.
From side conversations with @MEBirnbaum to an incredible result for patients. So proud of the Kelonia team for all the hard work it took to make this real.
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Check out @Steph_Gaglione's amazing preprint introducing a highly scalable (and inexpensive) approach to TCR synthesis that enables library-on-library screening of TCRs + antigens 👇!
Thrilled to share our preprint! We introduce TCRAFT, a method to assemble tens of thousands of TCRs at <$1 each, unlocking high-throughput functional TCR screening from single-cell data.
🧵@kochinstitute @MEBirnbaum @MITChemE @MIT
biorxiv.org/content/10.1101/…
An incredibly impressive body of work from the newly-minted PhD @calebrperez comparing clinical candidate CAR-T architectures head-to-head at single cell resolution, shedding light on mechanisms of differential CAR-T efficacy in vivo with insights into better construct design 🚗
Excited to share some of my PhD work was pre-printed! Using single-cell sequencing, we took a deep look at a library of CAR signaling architectures to try to identify signal-intrinsic drivers of CAR-T function🧵👇 @MEBirnbaum @kochinstitute @MITdeptofBE
biorxiv.org/content/10.1101/…
The authors then applied their TScan-II methodology to uncover antigens in cancer, autoimmunity, & infectious disease across many different MHC class II alleles & TCRs
Their screens uncovered antigens recognized by clonally-expanded CD4+ T cells from Sjögren's syndrome patients
In sum, Dezfulian et al. have successfully re-centaured T cell antigen discovery around CD4+ T cells 😉
cell.com/cell-reports-method…
For their last trick🪄, the authors introduced the candidate human TCR antigen-binding variable region atop a murine TCR constant region resulting in a human-mouse hybrid TCR that reduces cross-reactivity with the endogenous TCR
They termed these chimeras "centaur T cells"🏃🐎
Wrote a Spotlight piece together w/ lab mate @amandaochan & @MEBirnbaum covering an impressive new methodology from @elledge_stephen's group that enables MHC class II antigen discovery for CD4+ T cells called TScan-II
cell.com/cell-reports-method…
They also needed to introduce a reporter of T cell antigen recognition
The reporter is an infrared fluorescent protein (IFP) that only becomes fluorescent upon exposure to cytotoxic granzyme B (GzB), representing a functional & sortable readout of cognate CD4+ T cell recognition
But to do so, the authors needed to engineer both the antigen presenting cells (APCs), alongside the primary T cells used
For the APCs, they modified HEK-293 cells (eHEK-293-II) to lack MHC class I, but present MHC class II allele(s) of interest alongside appropriate machinery
TScan-II allows for genome-scale interrogation of MHC class II antigens using endogenous processing & presentation machinery of antigen libraries, alongside physiological T cell activation & degranulation (GzB) 👇
pubmed.ncbi.nlm.nih.gov/3801…
new @runthelistpod episode is now out hosted on @MHMedical's AccessMedicine webpage!
best part about it?
you can search for key words & phrases to more easily listen to high-yield content 🤯
accessmedicine.mhmedical.com…
We're back with another pod🎙️!
Ep 97: Approach to Dysphagia
accessmedicine.mhmedical.com…
Host @NavinKumarMD discusses dysphagia workup w/ RTL's own @WalkerReddMD
Blake Smith retweeted
1. ENTER #mRNAvaccines for #pancreaticcancer! Long-term #PDAC survivor story PART3.
"Do #PDACs REALLY have vaccine neoantigens (NAs)"? (aren’t they lowly mutated?)
If each patient = own NAs, how do you vaccinate?
Maybe mRNA? But how?
@Nature nature.com/articles/s41586-0…
👇🏽 [1/32]
had to come out of Twitter hibernation to highlight this out-of-the box use case for #PROTACs:
live-attenuated virus vaccines
Flu vaccines have a whole host of difficulties from vaccine manufacturing to antigenic drift & this approach simplifies it all
nature.com/articles/s41587-0…
influenza A virus expressing M1-ALAPYIP protein + a protease (TEV) tag can be made in cells expressing TEVp, but degraded in target cells that *lack* TEVp, but express VHL
thus, they generated fully-assembled influenza A virus whose Achilles heel is its small degron handle
