Nikolai Slavov Download

Nikolai Slavov

Professor,  Bioengineering
Founding Director,  Parallel Squared Technology Institute
Allen Distinguished Investigator,  Allen Frontiers Group
Director,  Single-Cell Proteomics Center
Affiliated Faculty,  Biology
Affiliated Faculty,  Chemistry and Chemical Biology

Contact

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Office

  • Mugar Life Sciences, Office 334
  • 617.373.6405

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Research Focus

Single-cell proteomics, immunology, cancer drug resistance, translational regulation, quantitative systems biology, mass spectrometry, RNA decoding, protein synthesis and degradation, macrophage polarization, neurodegenerative diseases

About

Nikolai Slavov received undergraduate education from MIT and a doctoral degree from Princeton University for characterizing the coordination of cellular growth with gene expression and metabolism.

The Slavov laboratory pioneered experimental and computational methods for single-cell proteomics and used them to connect protein covariation across single cells to functional phenotypes, including macrophage polarization, emergence of drug resistance priming, early mammalian development, and stem cell differentiation. These technologies provided a foundation for establishing Parallel Squared Technology Institute (PTI).

Prof. Slavov organizes the annual single-cell proteomics conference and contributes to organizing other leading conferences, including NeurIPS.

Education

  • PhD (2010), Botstein Laboratory, Princeton University
  • BS (2004), Biology, Massachusetts Institute of Technology

Honors & Awards

  • HUPO Discovery in Proteomic Sciences Award
  • 2022 College of Engineering Faculty Fellow
  • Allen Distinguished Investigator Award
  • Excellence in Mentoring Award
  • NIH Director’s New Innovator Award
  • SPARC Award from the Broad Institute of MIT and Harvard
  • Princeton University Dean’s Award
  • IRCSET Postgraduate Research Fellowship
  • Finalist in the Young European Entrepreneur Competition
  • Princeton Graduate Fellowship
  • MIT Undergraduate Fellowship
  • Eureka Fellowship for Academic Excellence
  • Bronze Medal in the 31st International Chemistry Olympiad
  • National Diploma for Exceptional Achievements in Chemistry

Teaching Interests

Leadership Positions

 

Professional Affiliations

Research Overview

Single-cell proteomics, immunology, cancer drug resistance, translational regulation, quantitative systems biology, mass spectrometry, RNA decoding, protein synthesis and degradation, macrophage polarization, neurodegenerative diseases

Single-cell proteomics by mass-spectrometry

Many biological processes stem from the coordinated interactions of molecularly and functionally diverse cells. However, this diversity is relatively unexplored at the proteome level because of the limitations of conventional affinity-based reagents for quantifying proteins in single cells. To alleviate these limitations, in 2017 our laboratory introduced Single Cell ProtEomics by Mass Spectrometry (SCoPE-MS). Since then, we developed more powerful and fully automated methods, including SCoPE2, pSCoPE, and plexDIA.

Single-cell proteomics by Mass-spec (SCoPE-MS)

Taking advantage of ideas for advancing data acquisition and interpretation, we developed next generation methods that increase the sensitivity, data completeness and flexibility of single-cell protein analysis. These allow prioritization of thousands of proteins and highly parallel analysis of both single-cells and peptides. All of these methods can be implemented using accessible commercial equipment.

Single-cell proteomics by Mass-spec

Ribosome-mediated translational regulation

All living cells must coordinate their metabolism, growth, division, and differentiation with their gene expression. Gene expression is regulated at multiple layers, from histone modifications (histone code) through RNA processing to protein degradation. While most layers are extensively studied, the regulatory role of specialized ribosomes (ribosome code) is largely unexplored. Such specialization has been suggested by the differential transcription of ribosomal proteins (RPs) and by the observation that mutations of RPs have highly specific phenotypes; particular RP mutations can cause diseases, known as ribosomopathies, and affect selectively the synthesis of some proteins but not of others. This selectivity and the differential RP transcription raise the hypothesis that cells may build specialized ribosomes with different stoichiometries among RPs as a means of regulating protein synthesis.
While the existence of specialized ribosomes has been hypothesized for decades, experimental and analytical roadblocks (such as the need for accurate quantification of homologous proteins and their modifications) have limited the evidence to only a few examples, e.g., the phosphorylation of RP S6. We developed methods to clear these roadblocks and obtained direct evidence for differential stoichiometry among core RPs in unperturbed yeast and mammalian stem cells and its fitness phenotypes. We aim to characterize ribosome specialization and its coordination with gene regulation, metabolism, and cell growth and differentiation. We want to understand quantitatively, conceptually, and mechanistically this coordination with emphasis on direct precision measurements of metabolic fluxes, protein synthesis and degradation rates in absolute units, molecules per cell per hour.

 

Alternate RNA decoding

Amino acid substitutions may substantially alter protein stability and function, but the contribution of substitutions arising from alternate translation (deviations from the genetic code) is unknown. We have identified 60,024 high confidence substitutions corresponding to 8,801 unique sites in proteins from 1,990 genes. Some substitutions are shared across samples, while others exhibit strong tissue-type and cancer specificity. Surprisingly, products of alternate translation are more abundant than their canonical counterparts for hundreds of proteins, suggesting sense codon recoding. Recoded proteins include transcription factors, proteases, signaling proteins, and proteins associated with neurodegeneration. Mechanisms contributing to substitution abundance include protein stability, codon frequency, codon-anticodon mismatches, and RNA modifications. Some substitutions are shared across samples, while others exhibit strong tissue-type and cancer specificity. Surprisingly, products of alternate translation are more abundant than their canonical counterparts for hundreds of proteins, suggesting sense codon recoding. Recoded proteins include transcription factors, proteases, signaling proteins, and proteins associated with neurodegeneration. Mechanisms contributing to substitution abun-dance include protein stability, codon frequency, codon-anticodon mismatches, and RNA modifications. We characterize sequence motifs around alternatively translated amino acids and how substitution ratios vary across protein domains, tissue types and cancers. Both the sequence and the tissue-specificity of alternatively translated proteins are conserved between human and mouse. These results demonstrate the contribution of alternate translation to diversifying mammalian proteomes, and its association with protein stability, tissue-specific proteomes, and diseases.

 

Slavov Laboratory

We aim to understand the rules governing emergent systems-level behavior and to use these rules to rationally engineer biological systems. We make quantitative measurements, often at the single-cell level, to test different conceptual frameworks and discriminate among different classes of models.

Slavov Laboratory

Selected Research Projects

Research Centers and Institutes

Department Research Areas

Selected Publications

Key Research Articles

Recent Research Articles

Faculty

Feb 26, 2024

Northeastern Among Top 100 Universities for Utility Patents

Northeastern University, recognized for its excellence in innovation and entrepreneurship, has once again been named one of the top 100 universities worldwide for securing utility patents by the National Academy of Inventors.

Faculty

Jan 22, 2024

Addressing Risk Factors and Potential Treatments of Alzheimer’s and Dementia

BioE Associate Professor Nikolai Slavov and Bouve Associate Professor Becky Briesacher provide insight into the differences between Alzheimer’s and dementia.

Faculty

Dec 07, 2023

2023 Stanford University Annual Assessment of Author Citations

The following COE professors are among the top scientists worldwide selected by Stanford University representing the top 2% of the most-cited scientists with single-year impact in various disciplines. The selection is based on the top 100,000 by c-score (with and without self-citations) or a percentile rank of 2% or above.

Faculty

Dec 04, 2023

Slowing the Progression of Alzheimer’s Disease

BioE Associate Professor Nikolai Slavov is investigating methods to slow the progression of Alzheimer’s, which is a specific form of dementia.

Spotlight Story

Oct 12, 2023

PhD Spotlight: Jason Derks, PhD’22, Bioengineering

Jason Derks’ PhD’22, bioengineering, research focused on developing new methods for high throughput proteomics and using them for quantifying the proteomes of single nuclei from macrophage cells responding to bacterial antigens. He developed technology he would call “plexDIA,” which he published in Nature Biotechnology in 2022.

Nikolai Slavov

Faculty

Aug 10, 2023

New Methods of Analyzing Single Cell Proteomics

Allen Distinguished Investigator and BioE Associate Professor Nikolai Slavov was awarded a patent for “Mass spectrometry technique for single cell proteomics.”

Faculty

Aug 08, 2023

Professor’s ‘Game-changing’ Alzheimer’s Research a Major Beneficiary of $50 Million Grant

A new research institute led by Allen Distinguished Investigator and BioE Associate Professor Nikolai Slavov is the principal beneficiary of a $50 million grant from two investors, Schmidt Futures and Citadel, to develop new techniques for studying Alzheimer’s disease.

Nikolai Slavov

Faculty

Apr 04, 2023

Extending the Sensitivity, Consistency and Depth of Single-Cell Proteomics

The laboratory of Allen Distinguished Investigator and BioE Associate Professor Nikolai Slavov published their research on “Prioritized Mass Spectrometry Increases the Depth, Sensitivity and Data Completeness of Single-Cell Proteomics” in Nature Methods.

Nikolai Slavov

In the Media

Mar 30, 2023

Schmidt Futures Gives $50M for Life Science Research Including Single-Cell Proteomics Institute

The GenomeWeb article “Schmidt Futures Gives $50M for Life Science Research Including Single-Cell Proteomics Institute” highlights the Parallel Squared Technology Institute (PTI), a new non-profit research institute recently launched by Allen Distinguished Investigator and BioE Associate Professor Nikolai Slavov and former bioengineering students Aleksandra Petelski, PhD’22, and Harrison Specht, PhD’22.

Nikolai Slavov

In the Media

Mar 17, 2023

PTI Launches To Scale Protein Analysis Towards Scientific and Medical Breakthroughs

Allen Distinguished Investigator and BioE Associate Professor Nikolai Slavov launched his new Parallel Squared Technology Institute (PTI) to catalyze a leap in biomedical research by enabling protein analysis with single-cell resolution at unprecedented throughput.

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