Slavov Laboratory

We report many proteins not predicted by the genetic code. They are stable & abundant O( 10³ ) copies / cell. Generative mechanisms include codon-anticodon mismatches & RNA modifications. Their abundance depends on codon frequency & protein stability. biorxiv.org/content/10.110…

Next week, @_AndrewLeduc will present at the CSHL (@cshlmeetings) Systems Biology: Global Regulation of Gene Expression meeting. His talk will focus on in vivo protein regulation in single cells, including results from this preprint: biorxiv.org/content/10.110…

An important reminder: Academia is not about publishing papers. It’s about creating knowledge and teaching it to the world. It’s about asking big bold questions and mentioning the next generation of intellectual leaders. The difference makes a huge difference.

When I think on the timescale of days and weeks, progress can be frustratingly slow. Shifting to the timescale of years, the progress is spectacular: Often faster than expected. Living through the arc of technology development has been awesome. The best is yet to come 🚀

Six years on from this perspective: science.org/doi/10.1126/sc… The technology has rapidly advanced and spread beyond a few pioneering labs. I am excited for the next phase, when the technology will increasingly enable mechanistic investigations & discoveries. 🚀

Here is a robust biochemical & functional difference between young and old mammalian cells: - The fraction of new amino acids incorporated into proteins. The difference is consistent, quantitative, cell-type specific, and deeply intriguing. What aging mechanisms cause it ? 1/

Most proteins in mammalian tissues are cleared in just a few days. That's a remarkable rate of degradation & rebuilding ! Interestingly, degradation rates vary significantly across the cell types within a tissue. biorxiv.org/content/10.110… 1/

At the same time, some proteins are very long-lived. Some persist as long as the organism itself. Protein lifetimes range from minutes to decades: ⏹️ That's a dynamic range of ~6,000,000. Lifetimes vary across cell types & states, and these dynamics are essential to life! 2/

Recently, the FDA granted Premarket Approval to IsoPSA for prostate cancer diagnosis. This approval signals a key direction: ◼️ Improved diagnostic specificity based on protein modifications (proteoforms). Let's elevate our assays -- and thinking -- to the proteoform level.

Excited about the progress of single-cell proteomic technologies reviewed in this @AnnualReviews article. These advances reflect synergistic work across our field, and the next waves of development will unlock deeper biological and biomedical insight. 🚀🔬

Molecular features of human pathological tau distinguish tauopathy-associated dementias 2/2 cell.com/cell/fulltext/…

Post-translational protein modifications underpin protein functions and dysfunctions. Naturally, proteoforms enable molecular disease stratification. This resource article maps 145 PTMs and 195 cleavage sites on tau and uses them as biomarkers for tauopathies. 1/2

I’m grateful to be named a Distinguished Professor by Northeastern University College of Engineering. This recognition reflects the support, collaboration, and creativity of many colleagues, students, and collaborators over the years. I’m thankful to be part of a community that values rigorous science, curiosity-driven research, and supportive mentorship.

This review reflects on a journey I’ve been lucky to witness closely: ◼️ The transformation of single-cell proteomics from a fragile idea into a powerful discipline. The technological progress towards deeper coverage and higher throughput is fast and exciting, but what excites me most is the biology: ◼️ the chance to move beyond associations and toward causal, mechanistic understanding built on direct protein measurements. None of this would exist without early pioneers who pushed the field forward when success was far from guaranteed, nor without sustained advances in instrumentation that dramatically improved ion utilization and sensitivity. I see this as a starting point, a promising start. The next phase of the field should focus on discovery: mechanisms, principles, and new quantitative and conceptual ways of thinking about cellular regulation. Onward. 🚀 1/2

Biology is not static -- proteins are constantly being made, modified, and destroyed as cells live, respond, and adapt. Each cell interacts with other cells and its matrix to shape its proteome and dynamic responses. That’s why understanding in vivo proteome dynamics at the level of individual cells is one of the most exciting frontiers in understanding biological systems. 1/2

The processes sculpting protein abundance in the brain.

Protein degradation is often considered a final step in gene expression regulation. It also regulates the first step: Transcription TFs (e.g. p53, HIF, Myc) are regulated by 𝐝𝐞𝐠𝐫𝐚𝐝𝐚𝐭𝐢𝐨𝐧-𝐠𝐚𝐭𝐞𝐝 𝐜𝐨𝐧𝐭𝐫𝐨𝐥: ⬛️ It confers advantages. blog.slavovlab.net/2025/08/16/pro…

A basic intro with some strategies how to avoid mistakes when using dimensionality reduction. 2/n youtu.be/nIB-WjWzDSc?si…

Woot woot! this is the I think 6th or 7th lab outside of us to successfully apply nPOP and the second to build on nPOP for new applications in the last ~2 months. So awesome to see!

𝐖𝐞 𝐨𝐟𝐭𝐞𝐧 𝐭𝐞𝐚𝐜𝐡 𝐭𝐡𝐞 𝐠𝐞𝐧𝐞𝐭𝐢𝐜 𝐜𝐨𝐝𝐞 𝐚𝐬 𝐮𝐧𝐢𝐯𝐞𝐫𝐬𝐚𝐥 𝐚𝐧𝐝 𝐬𝐞𝐭𝐭𝐥𝐞𝐝.  𝐈𝐭 𝐢𝐬𝐧’𝐭. A Nature article shows that even the most basic rules of RNA decoding can be more flexible -- and more surprising -- than we assume. In the unicellular parasite Blastocrithidia nonstop, all 64 codons can encode amino acids in internal regions of mRNA, including codons that normally act as universal stop signals. Remarkably, this is enabled not by changing the anticodon itself, but by altering tRNA structure, a shorter stem allows a single tRNA to decode multiple codons, revealing layers of regulation beyond the textbook genetic code. Specifically, the tryptophan-bearing tRNA present in B. nonstop retains the standard anticodon for ‘reading’ UGG, but it also recognizes the codon UGA. This tRNA is different from other tRNAs: the ‘arm’ that projects the tRNA anticodon is shorter than normal by one base pair. This ‘short arm’ feature greatly enhances UGA reading by the tRNA. 1/3

The regulation of protein abundance across single cells in a mammalian tissue youtube.com/watch?v=dnsYAs…