Ciaran Seath

Photoproximity labeling of c-Myc reveals SLK as a cancer specific co-regulator https://www.biorxiv.org/content/10.1101/2025.10.02.680136v1

Happy to share the finalized version of this work out in @angewandtechemie.bsky.social.

onlinelibrary.wiley.com/doi/10.1002/...

Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling Combining bioorthogonal protecting groups with localized catalysts that can unmask them is a powerful approach to spatially and temporally modulate molecular activity. Enzymes are appealing catalysts ...

Excited to share a new pre-print on a joint study between my group and @chembiobryan.bsky.social‬! Directed Evolution of Enzymes for Bioorthogonal Chemistry Using Acid Chloride Proximity Labeling. chemrxiv.org/engage/chemr...
1/n

Post-Translational Modifications Remodel Proteome-Wide Ligandability Post-translational modifications (PTMs) vastly expand the diversity of human proteome, dynamically reshaping protein activity, interactions, and localization in response to environmental, pharmacologi...

Excited to share a new preprint from the lab. We show that PTMs like phosphorylation & glycosylation dynamically reshape proteome-wide ligandability in cells, including proteins like KRAS. Great collaboration with the Huang Lab, @forlilab.bsky.social and BMS. www.biorxiv.org/content/10.1...

Eragon series is good. Bartimaeus also good.

Photochemically Enabled Total Syntheses of Stemoamide Alkaloids Photochemical transformations continue to serve as powerful synthetic tools for rapid chemical synthesis and diversification. Recent developments in photoredox and photochemical reactivity have captur...

Very cool from Nicewicz lab pubs.acs.org/doi/10.1021/...

Crazy new pre-print from TSRI: fix whole mice, clear them transparent, click on fluorophores, & use light sheet microscopy to visualize where drugs bind throughout the body. Find ibrutinib-yne in low BTK heart & blood vessels, correlates with cardiac side effects.

www.biorxiv.org/content/10.1...

Engineered Proteins and Chemical Tools to Probe the Cell Surface Proteome The cell surface proteome, or surfaceome, is the hub for cells to interact and communicate with the outside world. Many disease-associated changes are hard-wired within the surfaceome, yet approved drugs target less than 50 cell surface proteins. In the past decade, the proteomics community has made significant strides in developing new technologies tailored for studying the surfaceome in all its complexity. In this review, we first dive into the unique characteristics and functions of the surfaceome, emphasizing the necessity for specialized labeling, enrichment, and proteomic approaches. An overview of surfaceomics methods is provided, detailing techniques to measure changes in protein expression and how this leads to novel target discovery. Next, we highlight advances in proximity labeling proteomics (PLP), showcasing how various enzymatic and photoaffinity proximity labeling techniques can map protein–protein interactions and membrane protein complexes on the cell surface. We then review the role of extracellular post-translational modifications, focusing on cell surface glycosylation, proteolytic remodeling, and the secretome. Finally, we discuss methods for identifying tumor-specific peptide MHC complexes and how they have shaped therapeutic development. This emerging field of neo-protein epitopes is constantly evolving, where targets are identified at the proteome level and encompass defined disease-associated PTMs, complexes, and dysregulated cellular and tissue locations. Given the functional importance of the surfaceome for biology and therapy, we view surfaceomics as a critical piece of this quest for neo-epitope target discovery.

Excited to share that our cell surface proteome review is now online on Chemical Reviews! 🥰 We highlight recent advances of techniques mapping cell surface protein expression, protein-protein interactions, extracellular PTMs and MHC complexes. @jimwellsucsf.bsky.social pubs.acs.org/doi/10.1021/...

Proteome-Wide Discovery of Degradable Proteins Using Bifunctional Molecules Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among ...

Happy to share a new preprint from our group in collaboration with AbbVie led by graduate student @inesforrest.bsky.social

www.biorxiv.org/content/10.1...

Congrats!!!

Absolutely honored to be selected 2025 CAS Future Leaders! Congrats to all the cohort and I look forward to join you in upcoming events! 🥳

Thanks Neel!! Following behind you and Tom’s foundation last year.

New Preprint from my group! We develop a systems level proximity labeling platform to study MOA of transcriptionally active drugs. In collaboration with the Rumbaugh lab, we employ this to deorphan a candidate ligand to treat neurodevelopmental disorders. www.biorxiv.org/content/10.1...

Discovery of a CNS active GSK3 degrader using orthogonally reactive linker screening Bifunctional targeted protein degraders, also known as Proteolysis Targeting Chimeras (PROTACs), are an emerging drug modality that may offer a new approach to understand and treat neurodegenerative d...

Excited to share the Farnaby Group’s first pre-print, detailing our approach to plate-based bifunctional chemical probe discovery, identifying a brain active PROTAC directly from a single screen. 1/7

chemrxiv.org/engage/chemr...

Deep-Red and Ultrafast Photocatalytic Proximity Labeling Empowered In Situ Dissection of Tumor-Immune Interactions in Primary Tissues Immunotherapy efficacy in solid tumors varies greatly, influenced by the tumor microenvironment (TME) and the dynamic tumor-immune interactions within it. Decoding these interactions in situ with minimal interference with native tissue architecture and delicate immune responses is critical for understanding tumor progression and optimizing therapeutic strategies. Here, we introduce CAT-Tissue, a novel deep-red photocatalytic proximity labeling method that enables ultrafast, high-resolution profiling of tumor-immune interactions in primary tissues. By leveraging nanobody-Chlorin e6 as the photocatalyst and biotin-aniline as the probe, CAT-Tissue enabled the rapid and comprehensive detection of various tumor-immune interactions in both coculture systems and primary tumor sections. Coupled with bulk RNA-sequencing, CAT-Tissue revealed distinct gene expression patterns between tumor-neighboring and tumor-distal lymphocytes, highlighting the recognition and immune responses of tumor-neighboring CD8+ T cells, which exhibited activated, effector, and exhausted phenotypes. By leveraging a deep-red photocatalytic proximity cell labeling strategy with excellent tissue penetration and biocompatibility, CAT-Tissue offers a nongenetically encoded platform with high sensitivity and spatiotemporal controllability for rapid profiling tumor-immune interactions within complex tissue environments in situ, which may advance our understanding of tumor immunology and guide the development of more effective immunotherapies.

See also this awesome work from Peng Chen and Xinyuan Fan who published a similar method earlier this week. pubs.acs.org/doi/10.1021/...

Multiprobe Photoproximity Labeling of the EGFR Interactome in Glioblastoma Using Red-Light Photocatalytic proximity labeling has emerged as a valuable technique for studying interactions between biomolecules in a cellular context, providing precise spatiotemporal control over protein labeling. One significant advantage of these methods is their modularity, allowing the use of a single photocatalyst with different reactive probes to expand interactome coverage and capture diverse protein interactions. Despite these advances, fewer methods have been developed using red-light excitation, limiting the use of photoproximity labeling in more complex media such as tissues and animal models. Herein, we develop a platform for proximity labeling under red-light excitation, utilizing a single catalyst and two distinct probe types. We first design a carbene based labeling system that utilizes sulfonium diazo probes. This system is successfully applied on A549 cells to capture the interactome of epidermal growth factor receptor (EGFR) using a Cetuximab-Chlorin e6 conjugate. Benchmarking against established techniques indicates that this approach performs comparably to leading carbene-based proximity labeling methods. Next, we leverage the strong singlet oxygen generation (SOG) ability of Chlorin e6 to establish an alternative labeling system using aniline and hydrazide probes. EGFR directed chemoproteomics experiments reveal significant overlap with the carbene system, with the carbene approach capturing a subset of interactions identified by the SOG system. Finally, we deploy our approach for the characterization of EGFR in resected human glioblastoma (GBM) tissue samples removed from distinct locations in the same tumor, representing the tumor’s infiltrating edge and its viable center, identifying several GBM specific interacting proteins that may serve as a launch point for future therapeutic campaigns.

Our first paper is out today in @jamchemsoc.bsky.social!
This is the beginning of a long journey for us, to study heterogeneity in GBM patient samples.
First step was to figure out some chemistry to enable us to look at this challenging problem.

pubs.acs.org/doi/10.1021/...

There is no need for different names for different flavors of display item in journals. Figures, Schemes, Tables, etc. can all just be called Figures and nothing is lost

Check out our web tool for searching for interactors of your favorite cell surface protein, developed by undergrad Pinyu Liao and postdoc postdoc Brendan Floyd @stanford-chemh.bsky.social

cellsurfacemap.org

"Imagine a DAPI-like stain, but for the extracellular matrix." That's basically how this work was pitched to me by Kayvon and Antonio a year or so ago. Now the final product really delivers. Read about their versatile label for ECM in living tissues here: www.nature.com/articles/s41...

Applications for the 2025 Bioorganic GRC are now live! Here is the link where you can check out the current line-up:

grc.org/bioorganic-c...

Come hang with me and @zhilindseylin.bsky.social at the 2025 Bioorganic Chemistry GRS! It’ll be a weekend full of excellent science and even more excellent people. The GRS is one of my favorite weekends of the year and we’re looking forward to another seminar full of amazing, trainee-led science!