Pombo Lab

Pombo Lab

Epigenetic Regulation and Chromatin Architecture

Profile

Our group is interested in understanding the interplay between gene regulation and genome architecture, towards defining rules and principles of genome function.

We study mechanisms of gene expression at multiple levels, from the local action of transcription factors, to long-range chromatin looping events that connect regulatory DNA sequences with the genes they regulate, to how whole chromosomes are positioned within cell nuclei. Binding of transcription factors at regulatory sequences helps recruit chromatin remodelers and the transcription machinery to transcription sites.

Upon recruitment, RNA polymerases either remain primed for subsequent activation (e.g. after environmental stress, during differentiation or disease), or directly transcribe the DNA template into RNA molecules, which code for proteins or for structural RNAs that constitute many enzymatic complexes.

An increasingly important aspect of gene regulation is the three-dimensional folding of the genome, and the mechanisms that control physical contacts of distant regulatory DNA sequences with gene promoters to activate gene expression. To directly measure genome topologies, our group developed Genome Architecture Mapping (GAM).

Our long-term strategy for unravelling the principles of genome function in higher eukaryotes aims to integrate multiple parameters, which is becoming increasingly possible with state-of-the-art developments in single cell genomics, molecular biology, epigenetics, nuclear imaging, and genetics.

Team

Group Leader

Scientist

Secretariat

Technical Assistants

Staff

PhD student

Graduate and Undergraduate

Alumni

year             name and position          current position
2022 - 2023

Lilith Klaus

BSc student

 
2022

Julia Markowski

Postdoc

Postdoctoral fellow, Blavatnik Institute of Biomedical Informatics, Harvard Medical School, Boston, US (with Peter Park)
2022

Mattia Conte

Postdoc

Postdoctoral fellow (Nicodemi lab), Naples University, Naples, IT
2022

Federico Billeci

MSc student

Data Scientist, Integra Therapeutics, SP
2022

Berta Jimenez-Alfaro Hacha

MSc student

Pombo lab, MDC, DE
2019 - 2022

Jennifer A. Giannini

PhD student (Fullbright Scholar 2019)

Scientific content creator, Labforward, Berlin, DE
2021

Simona Bianco

Postdoc

Assistant Professor, Naples University, Naples, IT
2021

Chloe Tang

MSc student

PhD student, Rippe lab, DKFZ, Heidelberg, DE

2020 - 2021

Lavanya Iyer

Postdoc

Task Force Lead, Single-cell Omics, Evotec, Göttingen, DE
2019 - 2020

Cleis Battaglia

MSc student

PhD student, Marenduzzo lab, Univ. Edinburgh, UK

2021

Rita Moldovan

BSc student

 
2017 - 2021

Ehsan Irani

Postdoc

Senior Data Scientist, IntelliSense.io
2015 - 2021

Gesa Loof

PhD student / Postdoc

Postdoctoral fellow, Inst. Biology Development, Marseille, FR (with Thomas Lecuit)
2014 - 2020

Ana Miguel Fernandes

PhD student / Postdoc

Data scientist, OLX Group, Berlin, DE
2014 - 2020

Rieke Kempfer

PhD student / Postdoc

NGS specialist, SOPHiA Genetics, Geneva, Switzerland
2018

David Pride

MSc student

Medical Trainee, Texas Tech School of Medicine, El Paso, US
2018

Vahid Assimi

MSc student

PhD student, Hinsz lab, MPI Molecular Genetics, Berlin, DE
2015 - 2018

Konstantina Skourti-Stathaki

Postdoc

Principal Scientist, RNA Biology, MiNA Therapeutics, London, UK
2012 - 2018

Elena Torlia Triglia

PhD student /Postdoc

Postdoctoral fellow, Broad Institute, Boston, US (with Brad Bernstein)
2014 - 2018

Giulia Caglio

PhD student 

Full Stack Data Scientist, Consultant, Catenion, Berlin, DE
2014 - 2018

Marta Slimak-Mastrobuoni

Postdoc

Commercial Development Manager Europe, Sterilex, Berlin, DE
2013 - 2018

Dorothee Krämer

PhD student

Global Medical Grant Developer, Medscape, Grenoble, FR
2017

Franka Rang

MSc student

PhD student, Kind lab, Hubrecht Institute, Utrecht, NL
2017

Daria Ivanove

BSc student

 
2013 - 2017

Tiago Rito

Postdoc

Postdoctoral fellow, Crick Institute, London, UK (with James Briscoe)
2010 - 2017

Joao Dias

PhD student / Postdoc

Postdoctoral Fellow, Montpellier, FR (with Monsef Benkirane)
2008 - 2017

Carmelo Ferrai

Postdoc

Postdoctoral Fellow, Göttingen, DE (with Philipp Stroebel)
2016

Leonid Serebreni

MSc student

Postdoctoral Fellow, Junker lab, MDC, Berlin, DE
2016

A. Julieta Ramirez Cuellar

MSc student

Business co-founder, Guanajuato, Mexico
2013 - 2016

Markus Schüler

Postdoc

Head of Data Strategy, mobile.de/eBay, Berlin, DE
2013 - 2016

Mariano Barbieri

Postdoc

Postdoctoral Fellow, Göttingen, DE (with Argyris Papantonis)
2011 - 2016

Robert A. Beagrie

PhD student / Postdoc

Group Leader, Sir Henry Dale fellow, Wellcome Trust Centre, Oxford, UK
2008 - 2014

Kelly J. Morris

PhD student / Postdoc 

Career break
2015

Marisa Saponaro

MSc student

Clinical Research Associate, Syneos Health Clinical Solutions, Rome, IT
2009 - 2013

Kedar Natarajan

PhD student / Postdoc

Associate Professor, University of Southern Denmark, Odense, Denmark
2000 - 2013

Sheila Q. Xie

Postdoc

Senior Postdoctoral Fellow, MRC-LMS, UK (with Michelle Percharde)
2008 - 2013

Liron-Mark Lavitas

PhD student / Postdoc

Clinical Project Assistant, PPD Pharmaceuticals, Munich, DE
2007 - 2013

Inês de Castro

PhD student / Postdoc

Lecturer, Brunel University London, UK
2011 - 2013

C. Ribeiro de Almeida

Postdoc

Group Leader, Babraham Institute, Cambridge, UK
2008 - 2012

Mita Pabari

Postdoc 

Medical Writer, MIMS (Hong Kong) Limited
2007 - 2012

Inês de Santiago

PhD student / Postdoc

Senior Principal Scientist – Computational Biology, e-Therapeutics PLC, Oxford, UK
2007 - 2011

Emily Brookes

PhD student / Postdoc

Lecturer in Biomedical Research & Group Leader, University of Southampton, UK
2004 - 2010

Andre Möller

Postdoc

Assistant Editor, BMC Biology, BioMed Central 
2009

Patrizia Beolchi

MSc student

Clinical Trial Manager, Medpace, London, UK
2008

Kelly J Morris

MRes student

 
2003 - 2008

Miguel R. Branco

PhD student / Postdoc

Reader, Queen Mary University London, Blizard Institute, London UK
2007

Liron Mark Lavitas

MRes student

 
2007

Pippa Hadland (neé Clarke)

MRes student

 
2007

Jonathan Pavelin

MRes student

 
2003 - 2007

Julie K. Stock

PhD student / Postdoc

Biotech and Pharma Consultant, Freelance and Blue Hearth Diagnostics, UK
2006

Emily Brookes

MRes student

 
2006

Nikolay Popov

MRes student

 
2005

Claire Mitchell

MRes student

 
2005

Edward Andres

MRes student

 
2001 - 2004

Pascale V. Guillot

Postdoc

Professor of Stem Cell and Gene Therapy, UCL Great Ormond Street Institute of Child Health, London, UK
2000 - 2004

Sonya Martin

PhD student 

Microscopy Support Officer, Microscopy Academic Units, University of Southampton, Southampton, UK
2003

Julie K. Stock

MRes student

 
2002

James Dixon

MRes student

 

 

Research

Our main goal is to unravel the diverse mechanisms of mammalian gene regulation and their roles in development and disease. Gene activation is controlled locally through transcription factors, chromatin modifiers, and the transcription and RNA processing machineries. Gene expression is also intricately regulated by the three-dimensional (3D) structure of the genome, which modifies the location of genes relative to activating or repressing biochemical environments. Repressing nuclear locations include the nuclear lamina and heterochromatin. Activating 3D genome conformations can work by regulating the physical proximity between regulatory regions and their responsive genes. As many disease-associated genetic variants fall in non-coding regulatory elements scattered in the genome, our work aims to advance the functional interpretation of the linear genome sequence. We especially put effort in devising experimental and computational approaches to map 3D genome structure in different cell types, in development and in disease, to study developmental and disease mechanisms, towards novel diagnostics, prognostics and therapeutics.

We have developed Genome Architecture Mapping (GAM), an orthogonal 3D genome folding mapping technology which yields fine maps of chromatin contacts from small cell numbers (500-1000), and is uniquely powerful to quantify different metrics of 3D genome structure, such as multiway contacts and chromatin melting. With immuno-GAM, we introduced the selection of cell types within complex tissues to enable the application of GAM in rare cells, such as dopaminergic neurons in the midbrain. GAM is an inherently suited platform for multimodal molecular phenotyping of biological samples, from genome sequence and 3D structure, to transcript and protein quantification. As a first step towards GAM multimodality, we have developed Oligo-Seq, a novel approach to detect minute amounts of specific RNA sequences within thin tissue cryosections, as used for GAM. We currently develop the application of Oligo-seq in spatial transcriptomics, especially in archival clinical samples (e.g. FFPE). By further developing multimodal integration of 3D genome topology, with the abundance of specific regulatory factors and gene expression, at the single-cell level, we aim to extract dynamic states of gene regulation and cause-effect relationships that connect 3D genome structure with gene expression. Ultimately, we seek to advance the interpretability of the linear genome sequence, to gain a deeper understanding of 3D genome regulation mechanisms in gene expression, and to advance their predictability.

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paper 2

 

 

 

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