jeannie carreiro

Recently committed to the Rockefeller University!

[Sanford Simon @SanfordMSimon]

Full manuscript available #CancerResearch #RareDiseases #PrecisionMedicine (9/9)
https://t.co/Z1CTg4EmXG

[Sanford Simon @SanfordMSimon]

For rare cancers like FLC where patient numbers are limited, having a dual mechanism in a single therapeutic could be a game-changer for clinical development. Our research offers new hope for patients with diseases driven by problematic proteins (8/9).

[Sanford Simon @SanfordMSimon]

This can be generalized to many targets with a random peptide libraries or protein language models with mutagenesis to tune the affinity. With a peptide you can use different E3 ligases that works in your tumor and your tumor is dependent upon (7/9)

[Sanford Simon @SanfordMSimon]

The combination accelerates protein elimination, reduces the chance of resistance, improves therapeutic window, and the peptide can be targeted to the subcellular compartment of the mutated protein (6/9)

[Sanford Simon @SanfordMSimon]

We could eliminate the cancer-causing fusion protein without affecting normal proteins and kill patient-derived tumors in mice. To reduce mutational escape, we added an antisense molecule (siRNA) to block production of the mutated protein (5/9).

[Sanford Simon @SanfordMSimon]

This binding peptide is extended with an enzyme that adds a tag called “ubiquitin” that sends DNAJB1::PRKACA to the proteasome, the cell's garbage disposal. Even though it binds BOTH to PRKACA and DNAJB1::PRKACA, it only degrades DNAJB1::PRKACA (4/9).

[Sanford Simon @SanfordMSimon]

Instead of blocking the mutated protein, we mark it for destruction and prevent new copies from being made with antisense. To target it for degradation, we used an altered a peptide that specifically binds to PRKACA (3/9).

[Sanford Simon @SanfordMSimon]

Here’s a new approach to treating diseases caused by mutated proteins, including the rare but lethal liver cancer fibrolamellar carcinoma (FLC). Many diseases are driven by mutations: sometimes a single change, sometimes two proteins fused together. (1/9)

[Sanford Simon @SanfordMSimon]

These are hard to drug: the mutated protein is similar to the normal protein. FLC is one such disease, driven by the fusion of piece of DNAJB1 to PRKACA, the catalytic subunit of protein Kinase A. (2/9)

[Dr. Lori L. Isom @LoriLIsom1]

A bittersweet goodbye as Joe Minton flies the nest for graduate school @Neuroscience_NU ! So proud of you.

[Mikołaj Słabicki @biomiko]

1/8 💡🦠 Can we harness human E3 ligases for antiviral defense? Are human E3 ligases involved in maintaining SARS-CoV-2 virus stability? Our pandemic research project is finally published! #COVID19 #E3Ligase https://t.co/wZdZL0rNIr