The Elowitz Lab at Caltech

This work was led by brilliant students Andrew Lu, Lukas Moeller, and Stephen Moore, and is a collaboration with
Hao Zhu and Dan Siegwart at UTSW.

If you have experience in animal cancer models and are interested in circuit therapeutics, please reach out.

In a mouse model of Ras-driven liver cancer, systemic treatment with the circuits (lower row) reduced tumor burden compared to untreated controls (upper row). Much more to explore.

We compared circuits (right) with Ras inhibitors (RMC-7977 and Sotorasib) by targeting mutant cells (magenta) co-cultured with wild-type Ras cells (green). Circuits were potent and selective.

We tried many, many, many circuit designs, eventually generating ones that sensitively discriminate Ras mutant cancer cells. We also generated protease-activated proteases to amplify weak oncogenic signals.

Why therapeutic circuits?
Sense-and-kill ≠ inhibit. Oncogene inhibition indirectly induces cell death, but is susceptible to resistance through compensatory signaling. Circuits directly rewire oncogenes to cell death --> less chance of resistance. Other benefits as well.

In this paradigm, engineered proteins are introduced into cancer and healthy cells using LNP-delivered mRNA. They then sense cancer markers (such as mutant Ras) and trigger engineered cell death effectors (caspases or gasdermins) only in cancer cells. (idealized schematic)

Synthetic biology could enable new types of programmable therapeutics. Our new preprint introduces synthetic protein circuits that selectively trigger cell death in Ras-mutant cancer cells, with interesting advantages compared to existing approaches.
www.biorxiv.org/content/10.1...

Congratulations to Dhiraj and the other amazing fellows

My first project in the @elowitzlab.bsky.social is finally out in @cellpress.bsky.social! We explore how competitive, "many-to-many" dimerization allows complex, multi-input, and cell-type-specific biochemical computations🧵↓

doi.org/10.1016/j.ce...

New study in @cellpress.bsky.social by Allen Distinguished Investigator @elowitzlab.bsky.social and collaborators explores the versatility of protein dimers. #FrontierScience

🔗 www.cell.com/cell/fulltex...

I really enjoyed reading this preprint, congrats @elowitzlab.bsky.social and team!

NIH cuts billions of dollars in biomedical funding, effective immediately The move halts a large slice of money for most universities and research institutions virtually overnight, imperiling vital research in everything from cancer to heart disease.

Another assault on US competitiveness at a time when biomedicine is roaring with innovation, an own-goal in a high-stakes international tournament. Of course the real losers are American people needing medicines and cures.

www.washingtonpost.com/health/2025/...

Really enjoying Uri Alon’s characteristically wonderful lectures on aging:
www.weizmann.ac.il/mcb/alon/cou...

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 gene expression and real-time fluorescence to modulation..

The lives of cells, recorded - Nature Reviews Genetics Recent advances in genome engineering are enabling the recording of cellular histories into genomes, with single-cell and spatial omics technologies enabling their reconstruction into cellular lineage...

"The lives of cells, recorded"--our new review on genomic recording systems and how they can reveal the dynamics of multicellular development. A pleasure to work on this with amazing colleagues from the Allen Discovery Center for Cell Lineage Tracing.
www.nature.com/articles/s41...

We are looking for new Bioengineering and Systems Biology faculty at University of Chicago, please apply and spread the news: apply.interfolio.com/157759

#science #faculty #biology #engineering #academia #technology #research #phd