Simanshu Dhirendra

Excited to share our latest work onll LZTR1 just published @ScienceMagazine!! A wonderful multidisciplinary collaboration between @simanshu's lab and our lab that provides structural understanding on RAS substrate and nucleotide specificity, and effect of mutations in LZTR1.

BBO-10203 is currently being evaluated in the Phase 1 BREAKER-101 trial (NCT06625775) in patients with HER2+ and HR+/HER2- breast cancer, KRAS mutant colorectal cancer, and KRAS mutant non-small cell lung cancer.

This publication describes how BBO-10203 disrupts the RAS–PI3Kα interaction without impairing insulin signaling, resulting in broad antitumor activity across multiple cancer models. It also shows enhanced efficacy in combination with other targeted agents.

We are excited to share our collaborative work on the first-in-class RAS:PI3Kα breaker, BBO-10203, which has now been published online in @ScienceMagazine ! 🔗 Read the full article here: science.org/doi/10.1126/sc… BridgeBio Oncology Therapeutics (BBOT) @FredNatLab @Livermore_Lab

This work was led by Daniel Czyzyk and Wupeng Yan in the laboratory, in collaboration with RAS Initiative colleagues and researchers at Daiichi Sankyo.

Our findings reveal key interaction interfaces and isoform-specific differences in RAS-PI3Kα, highlighting its crucial role in activating the PI3K-AKT-mTOR pathway and providing a blueprint for designing isoform-specific inhibitors to target RAS- and PI3K-driven cancers.

Excited to share our latest research, "Structural Insights into Isoform-Specific RAS-PI3Kα Interactions and the Role of RAS in PI3Kα Activation," now published in @NatureComms 📖 Explore the full article here: nature.com/articles/s4146… @FredNatLab

Our structural-guided insights contributed to the design of BBO-8520, a first-in-class dual inhibitor targeting both GTP-bound (ON) and GDP-bound (OFF) KRAS G12C. Excited to see this work now published in @CD_AACR! @FredNatLab @BridgeBioPharma

@ktr_nakanishi Congratulations @ktr_nakanishi and @futianmin! 👏👏

The paper was out🎉 cell.com/cell/fulltext/…

Online Now: Functional and structural insights into RAS effector proteins dlvr.it/T9kDnf

Check out our latest review regarding the biology of RAS GTPase effectors! It was fun to write this with @AmMozzarelli and @simanshu for @MolecularCell. Bottom line: lots of knowledge on these proteins, but many questions that remain to be answered. cell.com/molecular-cell…

@ktr_nakanishi @OSU_CBC @OSU_RNA Congratulations Kotaro!🎉🥂

I’m pleased to announce that I was promoted to full professor. Thanks to all external reviewers, the RNA community, @OSU_CBC, @OSU_RNA, my colleagues, and our lab members! Research keeps stimulating and amplifying my curiosity.

@ktr_nakanishi @OhioState @OSU_CBC @OSU_RNA Congratulations Kotaro!🎉

It’s a great honor to receive the 2024 Early Career Innovator of the Year! I’m thrilled to explore tinyRNAs and cityRNAs! I want to thank ⁦the RNA community, my friends, @OhioState,⁩ @OSU_CBC, ⁦@OSU_RNA⁩, and my lab members!!

The three-part New Drugs on the Horizon Series at the AACR Annual Meeting 2024 wrapped up this morning. A total of 12 first-time disclosures were presented. bit.ly/3J8AmVM #AACR24

The collaborative work was led by Lorenzo Finci, Mayukh Chakravarti, Gulcin Gulten, @dailyusbalius, @domespo and other members of the RAS initiative @FredNatLab

Our work builds on previous structural studies by many other groups describing structures of HSP90 and CDC37 in complex with RAF1, or in complex with BRAF-V600E, with and without protein phosphatase 5.

Our latest work in ⁦@CommsBio⁩ describes the cryo-EM structure of the RAF1-HSP90-CDC37 complex. Insights from 1μs simulations and structural analysis reveal key interactions and the role of HSP90 and CDC37 in client folding. ⁩ nature.com/articles/s4200…

Our latest study in @ScienceAdvances delves into KRAS4a, an overlooked splice variant, alongside KRAS4b. We uncover their unique structural and functional traits, emphasizing how HVR variations modulate interactions with PDEdelta, RAF, and PI3K. #KRAS4a science.org/doi/10.1126/sc…