Karsten Householder

phd @stanfordimmuno | bs/ms @StanfordBioE |🌵to🌲

[Anusha Kalbasi @xrtcell]

Pleasure to share a tremendous body of work from @YangZhao102, who led the next chapter of the powerful orthogonal IL-2 technology from the Garcia Lab (where the innovative spirit is unmatched).
Grateful for this ongoing collaboration, stay tuned for more. https://t.co/2TLCe4JLyF

[Cancer Grand Challenges @CancerGrand]

📜New in @ScienceMagazine: not one but two papers from team MATCHMAKERS!

The labs of David Baker @UWproteindesign and Chris Garcia @StanfordEMED published work that could revolutionise immunotherapy.

The Baker lab unveil a generative AI pipeline to design precise binders for antigen-MHC complexes—paving the way for more accessible immunotherapies.

🔗Read more: https://t.co/iOr6dpvpL1

[Arthur Deng @arthurdeng0205]

Predicting how mutations affect protein binding is key for drug design—but deep learning tools lag behind physics.

StaB-ddG closes the gap: combining stability models + smart pretraining to match FoldX accuracy at >1000× the speed.
Paper: https://t.co/HFJVw5nSKX
Code: https://t.co/Y3z4EAsjbH

@brianltrippe and @karstenhouse_14 will be presenting this paper at #ICML2025 next week in Vancouver
Contact: [email protected]

[Aaron Ring @aaronmring]

Just a few months ago, the Baker and Garcia labs released con-concurrent preprints with incredible results. They designed de novo miniproteins that bound specific peptides presented in MHC-I.

Now let me show how you can use BindCraft at @AriaxBio to do the same thing.

[Karsten Householder @karstenhouse_14]

Check out @GitaAbhiraman’s latest work! Grateful to be a part of this all-star team

[Gita Abhiraman, MD, PhD @GitaAbhiraman]

Excited to share this work from the Garcia Lab out today in @NatureComms! We engineer "cytokine adaptors", molecular switches that simultaneously block a target cytokine while inducing local activation of alternative cytokine receptors. https://t.co/CYQzioKFmo

[Gita Abhiraman, MD, PhD @GitaAbhiraman]

Excited to share this work from the Garcia Lab out today in @NatureComms! We engineer "cytokine adaptors", molecular switches that simultaneously block a target cytokine while inducing local activation of alternative cytokine receptors. https://t.co/CYQzioKFmo

[Brian Naughton @btnaughton]

new blogpost on protein binder design https://t.co/Ai0UfHhRW1

[Brian L Trippe @brianltrippe]

🔥 Benchmark Alert! MotifBench sets a new standard for evaluating protein design methods for motif scaffolding.
Why does this matter? Reproducibility & consistent evaluation have been lacking—until now.
Paper: https://t.co/i2Lk3YZ24N | Repo: https://t.co/Xoun67eE9P
A thread ⬇️

[Robert Saxton @rsaxton_]

Exciting new work from @karstenhouse_14 and the Garcia Lab, congrats!!

[Vamsee_Mallajosyula @VMallajosyula]

Thrilled to share our latest work on broadening T cell help for developing better flu vaccines @ScienceMagazine @sarah_h_ross
Grateful for Mark Davis’s invaluable mentorship @StanfordMed @stanfordimmuno https://t.co/qeY0bQhXyU 1/n

[Biology+AI Daily @BiologyAIDaily]

De novo design and structure of a peptide-centric TCR mimic binding module

1. Introducing a groundbreaking peptide-centric TCR mimic (TCRm) with nanomolar affinity (Kd = 9.5 nM) for the NY-ESO-1 peptide presented by HLA-A*02. This de novo α-helical TCR mimic achieves precision targeting in cancer immunotherapy.

2. Key innovation: The TCRm adopts a rigid α-helical scaffold, engineered using RFdiffusion and ProteinMPNN, ensuring high peptide specificity while minimizing off-target effects, a critical challenge in current cancer therapeutics.

3. Structural breakthrough: The high-resolution (2.05 Å) crystal structure reveals a TCR-like docking mode, focusing on peptide-specific interactions with minimal flexibility, reducing potential for cross-reactivity.

4. Superior targeting: The TCRm was validated through yeast display, SPR, and in silico modeling, demonstrating potent binding to NY-ESO-1 with no detectable affinity for unrelated peptides presented by the same MHC molecule.

5. Off-target analysis: A structure-informed in silico screen identified two potential off-target peptides among 14,363 HLA-A*02 ligands. Experimental validation confirmed the specificity and therapeutic window of the TCRm.

6. Therapeutic potential: This TCRm can function as a bispecific T cell engager, effectively activating T cells against cancer cells presenting NY-ESO-1 while sparing healthy tissues.

7. Modular and efficient: Leveraging α-helical scaffolds over traditional antibody-based approaches, this design facilitates rapid development, modularity, and scalability, significantly accelerating therapeutic discovery.

8. Future vision: This work establishes a robust framework for engineering peptide-specific TCR mimics, paving the way for precision immunotherapies in oncology and beyond.

@arthurdeng0205 @karstenhouse_14 @stanfordimmuno
📜Paper: https://t.co/jDCky4NdYw

#CancerImmunotherapy #ProteinDesign #Bioinformatics #AI #PrecisionMedicine

[John Connolly @John_E_Connolly]

Amazing work from the Garcia Lab @StanfordMed https://t.co/JprqP2IB9Q #TCRtherapy

[Karsten Householder @karstenhouse_14]

We hope this approach demonstrates how in silico methods can fast-track the discovery of precision cancer medicines…more to come!

Huge thanks to all members of the Garcia Lab for their support 🙏🏻

[Karsten Householder @karstenhouse_14]

Proud to share early work from my 1st year in the Garcia Lab! 🧬 the tldr: in just a few months, we go from computational design —> real cancer-specific T cell engagers!

https://t.co/7GBYDF2Brj

[Karsten Householder @karstenhouse_14]

@aerin_yang Thanks Aerin!!

[Aerin Yang @aerin_yang]

Mind blowing paper from the Garcia lab by the one-and-only @karstenhouse_14 ! Congratulations to the entire team!

De novo design and structure of a peptide-centric TCR mimic binding module https://t.co/VvJF0ZtiCC

[Ron Alfa @Ronalfa]

Announcing OCTO-VirtualCell (vc) a multi-scale, multimodal transformer trained to predict gene expression for a virtual cell in cellular contexts within patient tissue samples. Complete wth the Celleporter demo app to explore the data!

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[Brian Naughton @btnaughton]

New blogpost: The ABCs of Alphafold 3, Boltz and Chai-1

https://t.co/YXKOrHNsZW

[Science Immunology @SciImmunology]

New research from @Stanford_MCP describes the structural mechanism that enables #adenoviruses to escape immunity by targeting #CD45 on T cells.

Read more in Science #Immunology: https://t.co/aLy45wPKRP

[Gita Abhiraman, MD, PhD @GitaAbhiraman]

Stanford Immunology Preview is open to prospective PhD students, especially from underrepresented backgrounds in STEM. The goal is to provide info to demystify the program and the admissions process. Apply to Preview here:
https://t.co/cHvGfnVQTw