Achievements
New Publication by Sidhant Kalia
RBP-ReguNet Doctoral Candidate Sidhant Kalia Publishes Spotlight Commentary in Cell Reports
We are delighted to share that Sidhant Kalia, one of our MSCA-DN Doctoral Candidates in the RBP-ReguNet project, has published a Spotlight commentary in Cell Reports* titled “Tumor growth going FAR with KRAS FARnesylation-induced phase separation”.
This commentary highlights and contextualises a major breakthrough published earlier this year in Cell* by Wang et al., which uncovered a previously unknown regulatory layer in KRAS biology: farnesylation-driven liquid–liquid phase separation (LLPS).
A new mechanism in KRAS activation
KRAS is one of the most frequently mutated oncogenes in human cancers, particularly in colorectal, lung, and pancreatic tumours. For decades, farnesylation — a lipid modification at the C185 residue in KRAS’s hypervariable region — was understood primarily as a signal for membrane anchoring, enabling KRAS to activate downstream signalling pathways such as MAPK.
Wang and colleagues now show that this same farnesylation modification also promotes the formation of cytoplasmic KRAS condensates through phase separation. These membraneless organelles:
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Recruit and cluster RCE1, the enzyme responsible for further KRAS processing
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Accelerate KRAS maturation and plasma membrane translocation
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Amplify KRAS signalling output, thereby fuelling tumour growth
Strikingly, the abundance of these condensates correlates with advanced tumour stage, invasion, metastasis, and poor patient prognosis in colon cancer — and the phenomenon appears relevant in other KRAS-driven malignancies as well.
Therapeutic implications: statins as KRAS condensate disruptors
Perhaps most excitingly, the study identified statins — widely used cholesterol-lowering drugs — as disruptors of KRAS phase separation. Among them, pitavastatin stood out for its ability to:
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Block KRAS condensate formation
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Suppress tumour growth in preclinical models
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Re-sensitise tumours resistant to KRAS G12C inhibitors (e.g. AMG 510)
This positions statins as promising candidates for combination therapies in KRAS-mutant cancers, an area of intense clinical interest given the historical difficulty of targeting KRAS directly.
Why this matters for RBP-ReguNet
Although this work centres on KRAS rather than RNA-binding proteins per se, it is directly relevant to RBP-ReguNet’s mission. The project aims to deconstruct and rewire RNA–RBP regulatory networks, many of which converge on signalling pathways such as MAPK — the very pathway activated by KRAS. Moreover, the concept that post-translational modifications can drive phase separation is highly relevant to our understanding of how RBPs form membraneless condensates (e.g. stress granules, P-bodies) to regulate RNA metabolism in health and disease.
Sidhant’s own doctoral research within RBP-ReguNet explores the role of RNA-binding proteins in MAPK signalling and their capacity to undergo condensation in cancer contexts. This Spotlight commentary reflects his growing expertise at the intersection of phase separation, signalling regulation, and cancer biology — areas that are central to the next generation of targeted therapies.
Read the publication
The Spotlight commentary is now available open access in Cell Reports:
🔗 https://www.cell.com/cell-reports/fulltext/S2211-1247(26)01002-8
Congratulations, Sidhant, on this excellent contribution to the scientific discourse!
RBP-ReguNet Doctoral Candidate Salma Hesse Featured Speaker at EFMC International Symposium on Medicinal Chemistry
We are thrilled to celebrate a major milestone for one of our RBP-ReguNet Doctoral Candidates!
Salma Hesse (DC10), based at the Università degli Studi di Milano (UNIMI), has been selected as a featured speaker at the prestigious EFMC International Symposium on Medicinal Chemistry (EFMC-ISMC).
Salma presented her cutting-edge research titled:
“Targeting RNA Binding Proteins: Advancing from Small Molecule Modulators to PROTACs”
Her work explores RNA-binding protein (RBP) modulators — a tough journey that started with the identification of a hit compound and evolved through medicinal chemistry and lead optimization – ultimately taking them toward an RBP-targeted degrader.
Hit → Lead Optimization → Lead → Degrader 🚀
Post on LinkedIn: https://lnkd.in/p/ewzWPGhV
Driving Innovation in European Doctoral Training
Participation in flagship international forums such as the European Federation for Medicinal Chemistry (EFMC) symposium highlights the caliber and impact of the research conducted by early-stage researchers across the RBP-ReguNet consortium.
“Salma’s achievement reflects her hard work, interdisciplinary dedication, and the collaborative strength of our consortium. Presenting doctoral research on a major international stage demonstrates how the Marie Skłodowska-Curie Actions network empowers young scientists to bridge fundamental RNA biology with translational medicinal chemistry.”
Congratulations, Salma, on this outstanding achievement!
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New Publication by Sidhant Kalia
New research alert!
Check out this recent study by our RBP-ReguNet DC Sidhant Kalia and colleagues, with last author Purusharth I Rajyaguru where the team uncovers how RNA-binding proteins Scd6 and its human ortholog LSM14A regulate translation during genotoxic stress.
Genotoxic stress triggers Scd6-dependent regulation of translation to modulate the DNA damage response
https://doi.org/10.1038/s44319-025-00443-3