Group lead (Structural Biology) at NCI RAS Initiative @FredNatLab; RAS/RAF/PI3K structural biology and drug discovery
Joined April 2009
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12 Photos and videos
Apr 22
Our new review titled "Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass," published today in the @Biochem_Journal Journal, published by the @BiochemSoc Society, and co-authored with @frankpmccormick
portlandpress.com/biochemj/a…
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Apr 22
Historically, the canonical RAS proteins—KRAS, HRAS, and NRAS—have been viewed as the primary drivers of signaling, with their GTP-bound forms assumed to uniformly activate all major downstream effector pathways at the plasma membrane. But is this model too simplistic?
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Apr 22
In this review, we revisit this framework and propose that RAS family members exhibit intrinsic effector preferences, pointing to a more specialized and organized signaling network that reflects a more structured division of labor within the network.
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Simanshu Dhirendra retweeted
11 Sep 2025
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.
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12 Jun 2025
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/scie…
BridgeBio Oncology Therapeutics (BBOT) @FredNatLab @Livermore_Lab
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12 Jun 2025
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.
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12 Jun 2025
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.
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9 Jan 2025
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/s41467-0…
@FredNatLab
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9 Jan 2025
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.
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9 Jan 2025
This work was led by Daniel Czyzyk and Wupeng Yan in the laboratory, in collaboration with RAS Initiative colleagues and researchers at Daiichi Sankyo.
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7 Dec 2024
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
6 Dec 2024
Now online in @CD_AACR: Discovery of BBO-8520, a First-in-Class Direct & Covalent Dual Inhibitor of GTP-Bound (ON) & GDP-Bound (OFF) KRAS G12C - by Anna Maciag, James Stice, Bin Wang, @frankpmccormick, Pedro Beltran, et al. doi.org/10.1158/2159-8290.CD… @FredNatLab @BridgeBioPharma
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Simanshu Dhirendra retweeted
17 Jul 2024
Online Now: Functional and structural insights into RAS effector proteins dlvr.it/T9kDnf
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Simanshu Dhirendra retweeted
17 Jul 2024
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/full…
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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
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2 Mar 2024
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/s42003-0…
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2 Mar 2024
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.
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2 Mar 2024
The collaborative work was led by Lorenzo Finci, Mayukh Chakravarti, Gulcin Gulten, @dailyusbalius, @domespo and other members of the RAS initiative @FredNatLab
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15 Feb 2024
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/scia…
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