Vicente Pelechano Garcia

Vicente Pelechano Garcia

Professor
Visiting address: Tomtebodavägen 23A (Gamma5), 17165 Solna
Postal address: C1 Mikrobiologi, tumör- och cellbiologi, C1 SciLife Pelechano, 171 77 Stockholm

About me

  • 2003 Biochemistry Graduate. University of Valencia, Spain.

    2009 PhD in Molecular Biology.University of Valencia, Spain.

    2009-2012 Postdoctoral training at EMBL Genome Biology Unit, Heidelberg, Germany.

    2012-2015 Staff Scientist at EMBL Genome Biology Unit, Heidelberg, Germany.

    2016-2020 Assistant Professor and Group Leader, Karolinska Institutet, Department of Microbiology, Tumor and Cell Biology (MTC).

    2025- Professor of RNA Biology at MTC, Karolinska Institutet.

    Photo credit of my portrait: Magnus Bergström

Research

  • Genomic Science and RNA Biology Lab

    One of the fundamental challenges in biology is understanding why identical cells respond differently to the same stimulus. While this variation can sometimes be attributed to changes in genetic material, even clonal cells—those with identical genomes—can exhibit diverse behaviors. To address this, we develop and employ advanced genomic technologies to investigate the mechanisms underlying differences in gene expression within clonal populations. Our research focuses particularly on understanding post-transcriptional RNA regulation and the interaction between RNA decay and the translation process. Additionally, our group is dedicated to developing innovative molecular diagnostic tools for infectious diseases. Specifically, we investigate:

    1.  Molecular bases of non-genetic cellular heterogeneity. We focus on understanding how single-cell variability, cellular plasticity and transcriptional memory contribute to the appearance of drug-tolerant cancer persister cells (i.e. those cells that, although genetically sensitive to a drug, do not respond to it). To reach that goal we combine the dissection of genetic factors controlling non-genetic heterogeneity with the development of novel genome-wide technologies to study this process.
    2. Crosstalk between ribosome dynamics and mRNA degradation. We have previously shown how the existence of widespread co-translational mRNA degradation allows to study ribosome dynamics by sequencing mRNA degradation intermediates (5P-Seq). Using that work as staring point, we to dissect the molecular crosstalk between mRNA degradation and ribosome dynamics in multiple organisms. We are characterizing how alterations in the translation process modulates mRNA stability and explore the utility of mRNA degradation signatures as reporters for cellular fitness in multiple organisms (from bacteria to cancer cells).
    3. Novel tools for molecular diagnosis. We are using our genomics expertise to improve and develop new molecular diagnosis and clinical genomic tools. We develop sequencing-based approaches to improve cancer-patient stratification and to accelerate the diagnosis of antimicrobial resistant infections.

    Our group is affiliated to MTC and SciLifeLab, where our lab is located.

Teaching

  • Since 2018 I co-direct the Karolinska PhD course “Genomics for Biomedical scientist: Handle your gene expression data (3230)”, co-directed with my MTC/SciLifeLab colleague Dr. Claudia Kutter.
    In addition, I teach in multiple Master and PhD courses in the field of Genomics, Gene Expression and Epigenetics.

Articles

All other publications

Grants

  • Swiss National Science Foundation
    1 April 2022 - 31 March 2026
    Appropriate regulation of gene expression, namely the production of functional proteins, is essential to the appropriate and timely development of all organisms. In eukaryotic cells, genes are transcribed in the nucleus, and the mRNAs are translated in the cytoplasm to produce proteins. Despite the separation of these different steps of gene expression in two different cellular compartments, evidence from the last decades has accumulated to indicate that the nuclear and cytoplasmic phases of gene expression are physically connected to ensure appropriate coordination and regulation. This project deals with the study of one complex, the Ccr4-Not complex, conserved across the eukaryotic kingdom, and a master regulator connecting the nuclear and cytoplasmic phases of gene expression. In the nucleus the Ccr4-Not complex promotes transcription elongation, impacts transcription-coupled repair mechanisms, regulates transcription factors and chromatin modifying components, regulates silencing and binds mRNAs during transcription to define their subsequent translation and turnover in the cytoplasm. In the cytoplasm it is important during translation for the production of soluble proteins, for co-translational processes, for deadenylation and for deadenylation-independent repression of translation initiation. The interconnections between all of these functions are still far from understood. This proposal has three defined aims centered towards understanding our recent finding that Not proteins form condensates and regulate translation elongation dynamics for production of soluble, functional and well assembled proteins. The first aim is to understand how the Not proteins regulate solubility of mRNAs, focusing on two mRNAs whose solubility is oppositely regulated by Not1 and Not4, then extending findings to global regulation of mRNA solubility by Not1 and Not4. The second aim is to define if Not proteins impact translation elongation dynamics directly, which functional domains of the Not proteins are relevant, if ribosome-associated targets of the Not4 E3 ligase contribute, the role of Not proteins in the nucleus, and how this correlates with changes in mRNA solubility. It will also explore the role of the RNA binding protein Puf3 for regulation of solubility and translation elongation dynamics of its targets by the Not proteins. Finally, the third aim is to characterize further Not protein condensates, their regulation, their dynamism and how they relate to translation elongation dynamics and mRNA solubility.These studies will be done in the model organism, the yeast S.cerevisiae, because of the simple and powerful genetic tools that we can combine with global approaches, basic molecular biology and biochemistry to confirm global findings. Moreover, over the years we have accumulated a large number of relevant strains and plasmids for this project, as well as expertise with yeast genetics. Our work should improve our understanding of how the Not subunits of the Ccr4-Not complex contribute to regulation of translational elongation, and gain new understanding on how this stage of gene expression is regulated in eukaryotic cells.

Employments

  • Professor, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 2025-
  • Professor, RNA Biology, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 2025-
  • Principal Researcher, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 2022-2025

Degrees and Education

  • Docent, Karolinska Institutet, 2023

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