Lukasz Bugaj

A bit late but…Tenured! Immense gratitude for those who got us here. Firstly the students/postdocs (too many to list!) who took a chance on an unproven lab and were unafraid to pursue some strange new ideas. I couldn't have predicted our path, and I couldn’t be more excited for what's next.

Also big thanks to former advisors David Schaffer and Wendell Lim for continued mentorship and for showing me how to do this job well.

A bit late but…Tenured! Immense gratitude for those who got us here. Firstly the students/postdocs (too many to list!) who took a chance on an unproven lab and were unafraid to pursue some strange new ideas. I couldn't have predicted our path, and I couldn’t be more excited for what's next.

Missed the deadline to submit an abstract to #FASEB Dynamics and Encoding in Cell Signaling (June 21-25)? Fear not: abstract deadline has been extended for 1 more week, until *Sunday May 10*. Several speaker slots and travel awards remain! events.faseb.org/event/Dynami... #CellSigSRC

🚨Preprint 2/2: Several studies implicate condensates in RTK fusion onco-signaling. So we were surprised to find that condensates are entirely dispensable😮(!). A study from proteins to mice, by dynamic duo @davidgonzmar.bsky.social and @trmumford.bsky.social. www.biorxiv.org/content/10.6... 👇

Summary: small fusion multimers are sufficient (tho not necessary!) to drive signaling and tumors. While condensates can form, they appear incidental. But if not condensates, then how do fusions signal from the cytoplasm? More to come here!

🚨Preprint 2/2: Several studies implicate condensates in RTK fusion onco-signaling. So we were surprised to find that condensates are entirely dispensable😮(!). A study from proteins to mice, by dynamic duo @davidgonzmar.bsky.social and @trmumford.bsky.social. www.biorxiv.org/content/10.6... 👇

4) Unexpectedly, even cytoplasmic *monomers* (const. active) can drive signaling and tumor formation, despite complete lack of multimerization that is essential for condensation.

🚨Preprint 2/2: Several studies implicate condensates in RTK fusion onco-signaling. So we were surprised to find that condensates are entirely dispensable😮(!). A study from proteins to mice, by dynamic duo @davidgonzmar.bsky.social and @trmumford.bsky.social. www.biorxiv.org/content/10.6... 👇

2) There is lots of active oncogene (pALK) in the diffuse phase, and when treated with ALK inhibitor, timescale of decay in the diffuse phase matches that of downstream signals, but decay in condensates is much slower.

🚨Preprint 2/2: Several studies implicate condensates in RTK fusion onco-signaling. So we were surprised to find that condensates are entirely dispensable😮(!). A study from proteins to mice, by dynamic duo @davidgonzmar.bsky.social and @trmumford.bsky.social. www.biorxiv.org/content/10.6... 👇

The condensate (large foci) model suggests that condensates of fusions (e.g. EML4-ALK) are an essential organizer of signaling in the cyto, in the absence of membrane. Causality is unclear though because perturb's of condensates are often also perturb's of kinase activity.

🚨New preprint(1/2)! We show that RTK fusion oncoproteins broadly suppress EGFR signaling. How? Sequestration of adapters as the shared principle. Led by superb PhD student Carol Gao. www.biorxiv.org/content/10.1... Implications for drug tolerance/resistance, and includes one big surprise🫧.👇

In sum, RTK fusions are simultaneously activators AND suppressors of mitogenic signaling. We expect future studies can exploit this suppressive behavior for biomimetic therapies designed to enhance killing & combat drug tolerance.

🚨New preprint(1/2)! We show that RTK fusion oncoproteins broadly suppress EGFR signaling. How? Sequestration of adapters as the shared principle. Led by superb PhD student Carol Gao. www.biorxiv.org/content/10.1... Implications for drug tolerance/resistance, and includes one big surprise🫧.👇

Targeted therapy (kinase inhibitors) releases Grb2 and relieves suppression. Potential therapeutic importance because drugs permit receptor signaling that promotes tolerance.

🚨New preprint(1/2)! We show that RTK fusion oncoproteins broadly suppress EGFR signaling. How? Sequestration of adapters as the shared principle. Led by superb PhD student Carol Gao. www.biorxiv.org/content/10.1... Implications for drug tolerance/resistance, and includes one big surprise🫧.👇

Main surprise: condensates (large foci) are *not* important for EGFR suppression. For EML4-ALK, condensates co-occur with suppression, but for most fusions -- no condensates. See concurrent preprint for more surprises on the role of condensates in fusions. www.biorxiv.org/content/10.6...

🚨New preprint(1/2)! We show that RTK fusion oncoproteins broadly suppress EGFR signaling. How? Sequestration of adapters as the shared principle. Led by superb PhD student Carol Gao. www.biorxiv.org/content/10.1... Implications for drug tolerance/resistance, and includes one big surprise🫧.👇

Previously we’d shown that EML4-ALK (onco-fusion) doesn’t only drive cancer signaling—it also suppresses EGFR, and suppression was reversed during therapy. www.nature.com/articles/s41.... Do other fusions also suppress EGFR? Also EML4-ALK formed condensates -- are condensates important?