The Nestor Lab (Decoding the Epigenetic Foundations of Human Health)

Dissertations from the Nestor lab.
Dissertations from the Nestor lab.

The Nestor Lab at LiU is fascinated by how epigenetic mechanisms, especially X-chromosome inactivation (XCI) in humans, shape development, health, and disease.

While XCI balances gene dosage between females and males, the incomplete or variable silencing of certain genes can lead to sex-specific differences in gene expression and contribute to sex-biased diseases such as autoimmune disorders like systemic lupus erythematosus.

We combine traditional molecular genetics with cutting-edge genomics and bioinformatics to study chromosomes and gene expression at an allele-specific level. Our toolkit includes nanopore long-read sequencing, single-cell multi-omics, and CRISPR-based epigenetic editing, letting us map, measure, and manipulate epigenetic states, including XCI, across the genome with high resolution.

We are also easily distracted by shiny new techniques, love developing our own methods, and can spend far too long testing the limits of the latest genomics technologies, because that’s half the fun of science!

Selected publications

Cover of publication 'A whole-organism landscape of X-inactivation in humans'
Björn Gylemo, Maike Bensberg, Colm Nestor (2025)

eLIFE , Vol.14 Continue to DOI

Cover of publication 'A landscape of X-inactivation during human T cell development'
Björn Gylemo, Maike Bensberg, Viktoria Hennings, Christina Lundqvist, Alessandro Camponeschi, Dóra Goldmann, Huan Zhang, Aida Selimovic, Antonio Lentini, Olov Ekwall, Colm Nestor (2024)

Nature Communications , Vol.15 Continue to DOI

Cover of publication 'TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia'
Maike Bensberg, Olof Rundquist, Aida Selimovic, Cathrine Lagerwall, Mikael Benson, Mika Gustafsson, Hartmut Vogt, Antonio Lentini, Colm Nestor (2021)

Proceedings of the National Academy of Sciences of the United States of America , Vol.118 Continue to DOI

Cover of publication 'A cover image of Science Advances.'
Karolos Douvlataniotis, Maike Bensberg, Antonio Lentini, Björn Gylemo, Colm Nestor (2020)

Science Advances , Vol.6 Continue to DOI

Cover of publication 'Cover image of Nature Methods.'
Antonio Lentini, Cathrine Lagerwall, Svante Vikingsson, Heidi K. Mjoseng, Dimitrios Karolos Douvlataniotis, Hartmut Vogt, Henrik Green, Richard R. Meehan, Mikael Benson, Colm Nestor (2018)

Nature Methods , Vol.15 , s.499-+ Continue to DOI

Cover of publication 'Cover image of Genome Research.'
Colm Nestor, Raffaele Ottaviano, James Reddington, Duncan Sproul, Diana Reinhardt, Donncha Dunican, Elad Katz, J Michael Dixon, David J Harrison, Richard R Meehan (2012)

Genome Research , Vol.22 , s.467-477 Continue to DOI

Most recent publications in LiU DiVA

2025

Maike Bensberg, Aida Selimovic, Lisa Haglund, Júlia Goldmann, Sandra Hellberg, Colm Nestor (2025) Exposing the DNA methylation-responsive compartment of the leukaemic genome in T-ALL cell lines support its potential as a novel therapeutic target in T-ALL CLINICAL EPIGENETICS, Vol. 17, Article 114 (Article in journal) Continue to DOI
Björn Gylemo, Maike Bensberg, Colm Nestor (2025) A whole-organism landscape of X-inactivation in humans eLIFE, Vol. 14, Article RP102701 (Article in journal) Continue to DOI

2024

Björn Gylemo, Maike Bensberg, Viktoria Hennings, Christina Lundqvist, Alessandro Camponeschi, Dóra Goldmann, Huan Zhang, Aida Selimovic, Antonio Lentini, Olov Ekwall, Colm Nestor (2024) A landscape of X-inactivation during human T cell development Nature Communications, Vol. 15, Article 10527 (Article in journal) Continue to DOI

2022

Rasmus Magnusson, Olof Rundquist, Min Jung Kim, Sandra Hellberg, Chan Hyun Na, Mikael Benson, David Gomez-Cabrero, Ingrid Kockum, Jesper N. Tegner, Fredrik Piehl, Maja Jagodic, Johan Mellergård, Claudio Altafini, Jan Ernerudh, Maria Jenmalm, Colm Nestor, Min-Sik Kim, Mika Gustafsson (2022) RNA-sequencing and mass-spectrometry proteomic time-series analysis of T-cell differentiation identified multiple splice variants models that predicted validated protein biomarkers in inflammatory diseases Frontiers in Molecular Biosciences, Vol. 9, Article 916128 (Article in journal) Continue to DOI
Olof Rundquist, Colm Nestor, Maria Jenmalm, Sandra Hellberg, Mika Gustafsson (2022) Progesterone Inhibits the Establishment of Activation-Associated Chromatin During T(H)1 Differentiation Frontiers in Immunology, Vol. 13, Article 835625 (Article in journal) Continue to DOI

Colm Nestor

Colm Nestor - Senior Associate Professor

My scientific path has always followed one central curiosity — how epigenetic mechanisms shape human biology. After studying Natural Sciences at Trinity College Dublin and completing master’s degrees in Computer Science at the University of Cork and in Bioinformatics at the University of York, I earned my PhD at the University of Glasgow and continued my postdoctoral training at the University of Edinburgh. These experiences brought together my interests in molecular genetics and computational analysis, setting the foundation for a career decoding the language of the human epigenome.

In 2012, I joined Linköping University in Sweden, where I established my independent research group to explore how DNA methylation and chromatin structure regulate human gene expression. Over time, my attention turned to one of the most striking examples of epigenetic regulation — X-chromosome inactivation (XCI), the process that equalizes gene dosage between males and females. My team now investigates how variations in XCI and other sex-chromosome-linked mechanisms may contribute to the marked differences in disease susceptibility between men and women.

This work, supported by a major ERC Consolidator Grant, seeks to uncover why females exhibit greater resistance to some infections yet higher rates of autoimmune disease, tracing the answer back to the molecular choreography of the X chromosome.

Alongside this, my lab continues to study DNA methylation in human CD4⁺ T cells, illuminating how immune cells acquire and maintain their specialized identities, and how these processes can go awry in disease. Earlier, my group also exposed a fundamental flaw in a widely used epigenomic method (DIP-seq), revealing pervasive false positives that had shaped much of the field’s literature — a discovery that reinforced my commitment to methodological rigor and reproducibility.

My research on methylation patterns in cancer and immunity connects back to the same core idea: that disease is often not written in the DNA code itself, but in how that code is read, modified, and remembered. As a Senior Associate Professor in Medical Genetics at Linköping University and recipient of the Onkel Adam Prize (2025), I continue to lead a multidisciplinary team probing how the epigenome encodes cellular identity, sex-specific biology, and the delicate balance between health and disease.

Björn Gylemo

Björn Gylemo - Postdoctoral researcher

I am a computational biologist and currently a postdoctoral researcher in the Nestor lab. I earned my Ph.D. from Linköping University, Sweden, in Colm Nestor’s lab, where I studied the dynamics of X-chromosome inactivation (XCI) in humans. My research focused on the fidelity of XCI escape during human T cell development, the variability of escape across tissues within individuals, and the frequency and genetic basis of constitutional XCI skew.

To investigate XCI escape, I employed integrative analyses of both direct measures, including single-cell and bulk allele-specific expression (the latter in females with completely skewed XCI), and indirect measures such as DNA methylation and sex-biased gene expression. For studying constitutional XCI skew, we developed a novel method, Tandem Repeat-based Identification of X-chromosome Inactivation (TRiXi), and but I have also leveraged long-read nanopore sequencing to assess XCI skew via allele-specific methylation.

Currently, I am exploring the research opportunities enabled by nanopore and long-read sequencing, including adaptive sampling strategies tailored to our experimental needs and applications in epitranscriptomics. My broader interests lie in genetics, with a particular focus on the sex chromosomes.

Outside of work, I enjoy spending time with my family, running, mountain biking, and hiking.

Lisa Haglund

Lisa Haglund - PhD student

I’m originally from Stockholm, Sweden, and completed my Bachelor’s degree in Biology and my Master’s degree in Experimental and Medical Bioscience at Linköping University. During my Master’s studies, I joined the Nestor Lab, where I spent two years exploring how DNA methylation contributes to hematological malignancies.

I am interested in the interplay between genetics and epigenetics, and how epimutations can mimic loss-of-function mutations, driving cancer progression. In December 2024, I began my PhD studies, where my research focuses on transgenerational epigenetic inheritance, aiming to understand why some Swedish families with a strong pattern of hereditary cancer show no detectable pathogenic germline mutations.

Outside the lab, I enjoy running and cycling and, most importantly, spending time with friends and family.

Engla Haglund

Engla Haglund - PhD student

I grew up in Stockholm and hold a bachelor's degree in Biotechnology, a Master's degree in Medical Biotechnology, and a Master of Science in Engineering (Biotechnology) from KTH (2025). During my master's studies, I spent a semester on exchange at Instituto Superior Técnico in Lisbon, which broadened my perspective on multiple scientific topics and further deepened my interest in genetics. For my master’s project, I joined the Nestor lab to investigate the role of TET2 in leukemic cell biology. After completing my master’s, I continued in the lab, combining bioinformatics and wet-lab work to study genetics and epigenetics from different angles and gain a comprehensive understanding of biological processes.

Sandra Hellberg

Sandra Hellberg - Assistant professor

I grew up in sunny Karlstad, Värmland, and later moved to Linköping to study biology at the Technical Faculty (LiU). After three years, I realized that I preferred spending my days in the lab rather than out in the forest, which led me to pursue a master’s degree in Medical Biosciences at the Faculty of Medicine. During my studies, I developed a strong interest in immunology and joined the late Professor Jan Ernerudh’s research group as a PhD student. My doctoral work focused on immune adaptations during pregnancy and on understanding why patients with multiple sclerosis often experience improvement during this period.

In the later stages of my PhD, I became increasingly interested in how epigenetic mechanisms influence immune regulation, with a focus on DNA methylation.

After earning my PhD in 2019, I joined Professor Mika Gustafsson’s team in Translational Systems Biology to strengthen my computational skills and further investigate the role of DNA methylation in immune-mediated diseases. During this time, I was awarded a prestigious postdoctoral fellowship from Hjärnfonden.

In 2023, I returned to the Faculty of Medicine as an Assistant Professor in Immunology and Epigenetics. Within the Nestor group, I continue to study how DNA methylation influences human health and disease, with a particular focus on cancer. My research bridges immunology, molecular biology, genetics, and epigenetics to understand mechanisms underlying complex diseases. I also lead a project on X-chromosome biology in the context of the female-predominant autoimmune disease systemic lupus erythematosus.

Shadi Jafari

Shadi Jafari - Principal Research Engineer

I am interested in understanding why females often resist infections better than males yet are more prone to autoimmune diseases. My research explores how the X chromosome shapes these differences through molecular and epigenetic regulation of immune cell development and behavior.

I studied medicine in Tehran, Iran, but soon became fascinated by the molecular logic behind how cells make decisions. This interest led me to pursue a master's degree in Genetics and Physiology and later a PhD in Neurobiology at Linköping University, Sweden, where I investigated how genes define sensory neuron identity in Drosophila. My doctoral work was recognized as the Best Medical Thesis of Linköping University in 2015.

After my PhD, I continued my research at Linköping University and New York University, exploring how chromatin and gene regulation shape neuronal development. My work focused on a newly identified neuron type in the fly optic lobe.

By combining developmental, anatomical, and transcriptomic analyses, I uncovered how these neurons originate, differentiate, and degenerate during metamorphosis. I also collaborated on a comparative study of olfactory sensory neurons in ants and flies, examining how neuronal activity and the co-receptor Orco influence their development and survival across species.

Now, as a Senior Research Engineer at Linköping University, I lead an ERC-funded project investigating X-chromosome inactivation (XCI)—the process that balances gene dosage between sexes—and how variation in XCI contributes to sex differences in immunity. My work bridges genetics, molecular biology, and medicine, connecting molecular mechanisms to the broader patterns seen in health and disease.

My long-term goal is to understand how chromatin structure and X-linked gene activity influence immunity, neurodevelopment, and aging, including in extremely preterm newborns and aging women.

Ingela Johansson

Ingela Johansson - Research Engineer

I have a Master’s degree in Engineering Biology from Linköping University, where I specialized in chemistry and biology.

I started working at Linköping University in 2004 in Professor Johnny Ludvigsson’s group, focusing on research into type 1 diabetes. Since 2023, I’ve been part of Colm Nestor’s group as a research engineer.

I’m responsible for keeping the lab running smoothly — making sure everything works as it should, helping PhD students with their projects, and working on a few of my own along the way.

Svenja Löffert

Svenja Löffert - PhD student

I grew up in Germany, where my fascination with science began at an early age. When I was eight, I often accompanied my mother to work and watched her perform lab experiments. Being surrounded by scientists and exposed to hands-on experiments sparked my curiosity about the immune system and the wonders of biology.

While living in the United States, I took advanced science courses and even performed animal surgeries, experiences that deepened my passion for medicine and research. Back in Germany, I pursued a Bachelor’s degree in Applied Biology at the University of Bonn, focusing on medical science and pharmacology. For my thesis, I joined a lab in Würzburg, where I investigated the role of T cells in acute Graft-versus-Host Disease—an exciting project that connected my interests in immunology and oncology.

In 2024, I completed the Experimental and Medical Biosciences program and joined the Nestor group for my thesis project. Continuing my focus on T cells, I shifted my research toward genetic and epigenetic mechanisms, specifically studying X-chromosome inactivation during T-cell differentiation. Today, as a PhD student in the group, I’m exploring how the second X chromosome influences CD4+ T-cell–mediated immunity and contributes to sex-based differences in immune responses.

Outside the lab, I love traveling the world, learning new languages, and immersing myself in different cultures. I also enjoy relaxing with a cozy mug of coffee and a fast-paced psychological thriller—or teaching myself how to play the guitar.

Ongoing Projects

XX-HEALTH

Women and men share remarkably similar immune systems, yet women often mount stronger immune responses. The secret may lie in the X chromosome, which carries many genes crucial for regulating immune cells like T-cells. Some of these genes escape X-chromosome inactivation (XCI), giving women’s immune cells an extra dose of key regulators that may fine-tune immune balance and resilience.

Our ERC-financed project, XX-Health, explores how these “escape” genes shape healthy T-cell function. We are developing TriX-Seq, an innovative tool to study how each X chromosome, maternal or paternal, is silenced in thousands of women. Rarely, some women silence the same X in all cells, offering a powerful natural model to study XCI’s impact on immune regulation.

Could this hidden X-linked biology explain why women fight infections differently? Might it reveal why autoimmune disorders are more common in females, and, of course, settle the question once and for all: is the “man-cold” real?

xSLE

Women often mount stronger immune responses than men, but that strength comes with a price: a higher risk of autoimmune disease. Why? Could the answer lie on the X chromosome?

In systemic lupus erythematosus (SLE), a disorder nine times more common in women, the immune system turns against the body, damaging tissues and organs. T-cells, key players in the immune response, behave differently in women with SLE, and the X chromosome seems to play a major role. Our project, xSLE, uses state-of-the-art genomics and gene-editing tools to study how the X chromosome is regulated in these women. We aim to uncover which genes escape inactivation and how this contributes to SLE development.

Could a misbehaving X chromosome explain why SLE affects women so much more often? Could unraveling this mystery help us develop new treatments and deepen our understanding of the unique dynamics of the female immune system?

HEREDITAS

Most cancers arise from random DNA mutations acquired during life, but in some families, cancer risk is inherited. These inherited mutations can dramatically increase the likelihood of developing cancers such as colorectal, breast, ovarian, or skin cancer. Identifying who carries these mutations can save lives through early screening or preventive treatment. Yet in most families with a clear cancer history, the disease-causing mutation remains unknown.

Our project uses cutting-edge genomic and epigenomic analysis, including ultra long-read sequencing, to uncover previously undetectable inherited changes that drive cancer risk. By revealing this hidden genetic and epigenetic variation, we aim to improve early diagnosis, guide preventive care, and better understand how cancer begins.

Ultimately, our goal is to give families the knowledge and tools to make informed health decisions, transforming inherited cancer risk from a life sentence into a chance for prevention.


EPIGENETICS CANCER THERAPIES

Cancer cells often carry abnormal DNA methylation, a chemical modification that can silence important genes and fuel disease. Drugs called DNA hypomethylating agents (HMAs), such as 5-azacytidine and decitabine, are standard treatments for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Combining HMAs with the pro-apoptotic drug venetoclax has recently improved treatment outcomes, but the precise molecular mechanisms behind this synergy remain unclear.

Our project at LiU-Cancer aims to unravel how HMAs and venetoclax interact at the molecular level. Surprisingly, early data suggest that removing DNA methylation may not drive the drugs’ effectiveness and might even dampen their synergy. By dissecting these mechanisms, we hope to refine HMA use, identify new ways to combine therapies, and expand precision medicine approaches to treat AML and other hematological cancers more effectively.

Could insights into DNA methylation hold the key to more precise, personalized cancer treatments?

News

A man in formal wear on stage

06 October 2025

Professors and award winners get their own Academic Ceremony

New professors will be inaugurated and award winners and Alumni of the Year will be celebrated at the Academic Ceremony on 10 October. Linköping University is growing, and as of this year two Academic Ceremonies will be held.

23 April 2025

The award winner: “Genetics is a bit like the Wild West”

Colm Nestor has been awarded the 2025 Onkel Adam Prize for outstanding research at the Faculty of Medicine and Health Sciences. One of his research areas is gender differences in susceptibility to autoimmune diseases and infections.

Several people engaging in lab work.

11 February 2025

Shedding light on sex differences in human disease

Researchers made an unexpected discovery while investigating genetically unique women. Their insights advance our understanding of our most enigmatic chromosome, the X chromosome.

Research Video

Flaw discovered in epigenetics research method

An error in one of the most widely used methods in epigenetics, DIP-seq, can cause misleading results, researchers at Linköping University, Sweden, have shown. This may have major significance in the research field, where “big data” and advanced methods of DNA analysis are used to study vast amounts of epigenetic data.

Funders

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