Creative proteomics

06/24/2026

Imagine having a map of every protein in the human body — across every major tissue, in health and in cancer. That's exactly what a team led by researchers at Westlake University and collaborators has just delivered.

Published in Nature this month, the team profiled 2,856 samples from 58 tissue types and 25 cancers using DIA-MS. They quantified 13,609 proteins and built a spatial atlas that reveals which proteins are unique to each tissue, how the proteome changes during development, and which cancer targets are shared across tumor types.

Key highlights: — 1,717 tissue-enriched proteins discovered — Brain tissue shows remarkable proteomic stability during development and cancer — 41 new high-priority drug targets identified on the cell surface of multiple cancers — A proposed drug repurposing strategy for endometrial cancer

This is the kind of resource that will transform how we approach biomarker discovery and drug development.

Read the full paper:

A spatially resolved map of the human proteome across a variety of healthy tissues and cancers provides wide-ranging insights in developmental biology and oncology, and could aid the identification of therapeutic targets and development of treatments for cancer.

06/24/2026

Cells have well-known ways to signal that they're under stress. But how do they signal that the stress is over?

A team led by researchers at Duke University and published in Nature Metabolism discovered an unexpected answer. They found that fatty acid synthase (FASN) — normally an enzyme for making fats — gets cleaved under stress recovery conditions. The cleaved fragment moves to the nucleus and activates a program that coordinates metabolic recovery.

Untargeted metabolomics was key to this discovery. By profiling the metabolic landscape of stressed and recovering cells, the team showed that FASN activation shifts the lipid profile from pro-apoptotic ceramides to protective phospholipids — changes that happen well before other recovery markers appear.

This study used Creative Proteomics' untargeted metabolomics service (LC-MS) to profile these metabolic changes.

Read the full paper:

Wei et al. show that proteolytic cleavage of fatty acid synthase (FASN) upon stress contributes to stress resolution. This role in stress resolution of the resulting C-terminal fragment of FASN is independent of its canonical function in fatty acid synthesis.

06/24/2026

Standard proteomics tells you how much of a protein is there — but not whether it's in the right shape to do its job. A protein can be present at normal levels but misfolded or unbound, and standard methods won't catch it.

LiP-MS (Limited Proteolysis Mass Spectrometry) solves this by using a controlled digest step under native conditions. Proteins in different conformational states show different cleavage patterns, and LC-MS/MS reads out these structural fingerprints across the entire proteome.

It's especially useful in drug discovery for studying how compounds change target protein conformation — a key part of understanding mechanism of action.

Our LiP-MS service at Creative Proteomics covers the full workflow: proteolysis optimization, LC-MS/MS acquisition, and structural change analysis.

Learn more: https://www.creative-proteomics.com/mass-target/lip-ms.htm

06/09/2026

Cells are supposed to get cysteine by importing cystine and reducing the disulfide bond. But what if both disulfide reductase pathways are knocked out?

A new Nature Chemical Biology paper answers that: a backup pathway activates — cell-autonomous, broadly expressed, inducible — that cleaves the C–S bond of cystine directly, bypassing the reduction step entirely.

Three reductase systems deleted (TrxR1, Trx1, GSR) from mouse liver. Cysteine production continues.

The implications reach into ferroptosis biology, glutathione synthesis, and the metabolic survival strategies of drug-resistant tumors. Cysteine's redox chemistry is more flexible than the textbook suggests.

Read the paper:

To obtain the semi-essential amino acid cysteine, cells assimilate its oxidized form, cystine, and then reduce its disulfide bond. By genetically deleting the disulfide reductase pathways from mouse liver, we uncovered an inducible, ubiquitous, cell-autonomous reductase-independent backup pathway fo...

06/09/2026

Most Plasmodium falciparum proteins had no known subcellular location — until now.

Chisholm et al. applied hyperLOPIT spatial proteomics to the malaria parasite's invasion-stage schizont and mapped 1,646 proteins across 24 distinct compartments, including sites inside the host red blood cell. Supervised machine learning handled the classification across this resolution — no organelle purification required.

The data reveals not just where proteins are, but which compartments are conserved across Plasmodium species and which are under ongoing evolutionary pressure. That's a roadmap for understanding — and targeting — what makes the parasite tick.

The method: density gradient fractionation + isotopic multiplexing + ML classification. High-resolution spatial proteomics without needing purified organelles. That's a general principle worth noting for anyone working on parasites, unusual cell types, or organisms where clean organelle isolation is impossible.

📄 Chisholm et al., Nature Communications, May 2026

👉 https://www.nature.com/articles/s41467-026-73664-2

Chisholm et al. use hyperLOPIT spatial proteomics to map 1646 Plasmodium falciparum proteins across 24 subcellular compartments, revealing evolutionary patterns that have shaped malaria parasite biology and ongoing adaptive responses.

06/09/2026

Spatial proteomics adds a dimension that metabolomics and lipidomics can't cover: where proteins are active, modified, and executing signaling programs in intact tissue.

Creative Proteomics' spatial proteomics platform includes:

▸ Untargeted discovery — MALDI-MSI with timsTOF fleX / RapifleX for broad, unbiased protein mapping ▸ Targeted validation — region-specific quantitation for known targets and pathways ▸ PTM spatial profiling — phosphorylation, glycosylation, acetylation mapped in tissue context (not just abundance) ▸ Imaging Mass Cytometry (IMC) — 40+ protein markers simultaneously, single-cell resolution, metal-tagged antibodies via Hyperion system

Fresh-frozen and FFPE compatible. Full-service from consultation to data analysis.

When you need to know not just what proteins are there but what they're doing and where — that's spatial proteomics.

👉 https://www.creative-proteomics.com/services/spatial-proteomics.htm

06/09/2026

Lipids don't distribute evenly. The biology is in where they accumulate — and at what concentration.

Creative Proteomics' Spatial Lipidomics service covers three MS imaging platforms:

▸ DESI-MSI — ambient ionization, minimal prep. Tissue stays intact for downstream H&E or IHC on the same slide. ▸ MALDI-MSI — Orbitrap/TOF-TOF resolution. Separates isobaric lipid species. Tunable spatial resolution. ▸ TOF-SIMS — subcellular to nanoscale. Membrane-level, organelle-level, single-cell-level lipid mapping.

Quantitative imaging uses isotope internal standard deposition — corrects ion suppression, delivers absolute concentration maps.

Service range: untargeted discovery → targeted panel → absolute quantitation → pathway mapping → comparative disease analysis.

Turnaround: 3–4 weeks. Free PhD consultation before project start.

Details: https://www.creative-proteomics.com/services/spatial-lipidomics.htm

06/09/2026

Where does the drug go? Where does the metabolite accumulate? Bulk mass spec gives you tissue averages. Spatial metabolomics gives you the map.

Creative Proteomics offers spatial metabolomics across three MS imaging platforms:

🔬 MALDI-MSI — 5–100 µm resolution, broad metabolite/lipid coverage 🔬 DESI-MSI — ambient ionization, no matrix prep, fast lipid mapping 🔬 LA-ICP-MS — trace element and metal spatial distribution

No labeling needed — detection by exact mass-to-charge ratio only.

Service options include untargeted discovery, quantitative imaging, single-cell spatial metabolomics, spatial drug distribution, and in situ PK&PD analysis.

Applications: oncology, neuroscience, drug ADME, infectious disease, plant science.

Details: https://www.creative-proteomics.com/services/spatial-metabolomics.htm

06/04/2026

Your phenotypic screen found a hit. Now what?

The target is unknown. The chemotype can't be derivatized — attaching a linker kills activity. And your academic collaborator only has one method available.

This is where Creative Proteomics' MassTarget™ Small-Molecule Target Identification platform changes the equation: six complementary chemoproteomics methods, two requiring zero compound modification.

🧪 The six methods in one platform:

🔹 Affinity Pull-Down MS — Gold standard for linker-tolerant compounds. Competitive elution for specificity. Results: 14 proteins enriched (LFQ >4), top target verified at SPR Kd = 340 nM.

🔹 Photoaffinity Labelling (PAL-MS) — For weak/transient interactions. UV crosslinking captures what washes away. Probe design + synthesis included.

🔹 Activity-Based Protein Profiling (ABPP) — Covalent inhibitor selectivity measured across enzyme-family panels. Result: >100-fold selectivity vs. 28/30 cysteine hydrolases — mapped to specific active-site residues.

🔹 Thermal Proteome Profiling (TPP) — NO compound modification. Unmodified compound + temperature gradient + proteomics = target melts differently. Result: primary target shift 4.2°C, plus 3 downstream pathway proteins identified in the same run.

🔹 Limited Proteolysis MS (LiP-MS) — Also NO modification. Detects allosteric binding via conformational changes. The method TPP doesn't replace — it complements.

🔹 Reactive Residue Profiling — Residue-level mapping of exactly which cysteines or lysines your electrophile modifies. Directly feeds med chem decisions.

The real advantage: validation is built in. BLI/SPR confirmation is part of the workflow — not something you coordinate externally. Sample requirements are SAR-friendly: 0.5–2 mg for TPP/LiP-MS, no derivatization needed.

Published example: Tao et al., Nature Communications 2023 — BioTAC proximity labeling validated on JQ1 (BRD2/3/4), Alisertib (Aurora A), and Trametinib (simultaneous MEK1/2 + KSR1 detection in one experiment). Proof that complementary methods beat any single approach.

When a phenotypic hit needs a target and SAR prohibits modification, this platform was built for exactly that.

👉 Full details: https://www.creative-proteomics.com/mass-target/small-molecule-target.htm

06/04/2026

Most drug discovery CRO workflows are fragmented by design — and it shows in the timeline.

Creative Proteomics' MassTarget™ platform takes the opposite approach: two interconnected pillars — Disease → Target and Target → Drug — with a single mass spectrometry backbone, a single informatics standard, and a single project scientist coordinating all experiments.

Why this matters, in concrete terms:

1. One data standard, one backbone. When target abundance from proteomics and thermal shift amplitude from TPP come from the same informatics platform, cross-experiment comparisons take hours, not weeks. No format translation. No integration meetings. The data is already unified.

2. Sample continuity. Protein purified for fragment screening is the same aliquot used for native MS confirmation. Lysate for thermal profiling comes from the same batch as quantitative proteomics. Sample never leaves the laboratory ecosystem — critical for precious patient-derived material.

3. Technical match, not catalog match. If the target has no known ligand (classic undruggable profile), the team doesn't force an off-the-shelf assay. They match the technology to the biology — native metabolomics pull-down, chemoproteomic reactivity mapping, or ion mobility screening — based on the molecular problem, not the available assay menu.

4. PROTAC/molecular glue end-to-end. Ternary complex stoichiometry, ubiquitination proteomics, global degradation selectivity — all under one roof. No splitting TPD characterization across three vendors.

What does this compress? A target-to-validated-hit transition that typically takes months across multiple CROs routinely completes in weeks on this platform.

If you're running a program where CRO fragmentation is costing you weeks in data reconciliation and sample logistics, this model is worth understanding.

👉 Full service overview: https://www.creative-proteomics.com/mass-target/drug-discovery.htm