Junior Research Group

Brain Mosaicism and Tumorigenesis

  • Functional and Structural Genomics
  • Junior Research Group
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Dr. Pei-Chi Wei

Principal Investigator

Not all brain cells have the same DNA. Some of these changes happen early in life and could play a role in the development of diseases like cancer. Our lab studies how these changes in DNA arise, how they are passed on to other cells, and how they spread in the brain.

An artistic representation of a brain divided into sections with different colors: blue, orange, and red. The brain appears to have stylized textures, and the design emphasizes creativity and intellectual activity. A simple black stem suggests the brain is growing from a surface, symbolizing the connection to knowledge.

Our Mission: Unraveling the Role of DNA Diversity in Brain Health

Illustration depicting a brain with colorful bar-like structures representing gene expression in different regions. To the right, additional graphs display varying gene activity levels indicated by contrasting colors, highlighting the relationship between genetic patterns and brain function.

Brain Development is a Dynamic Process  
The human brain is built from billions of neurons and astrocytes, generated through hundreds of divisions by neural progenitor cells. Remarkably, most of these cells form within just 24 weeks during fetal development. This process is carefully orchestrated in both time and space, shaping the ~400g newborn brain.

My lab explores fundamental questions: How do neural progenitor cells know when to stop dividing? Why and how do they extend their cell cycles? Does rapid cell division increase DNA damage in these cells? Understanding these mechanisms is key to uncovering how brain cancer begins, progresses, and evolves.

Methods and technologies 
We have developed experimental and analytical tools to uncover the interactions between the cellular machinery responsible for copying and reading DNA sequences. Using high-throughput sequencing technologies, we measure the timing and speed of DNA replication and examine the transcriptional "traffic" created by the machinery decoding DNA. 

Additionally, we create mouse models to investigate how neural stem cells compete for space and resources during early brain development. Our work also includes designing experimental systems that allow us to "travel back in time," tracing early developmental neural stem cell behaviors at later stages of life.

Goals and societal relevance 
Brain cancer prevention faces significant challenges due to our limited understanding of how early cellular processes contribute to tumor formation. Our mission is to bridge this gap by uncovering how neural stem and progenitor cells drive brain development while maintaining DNA integrity. By studying the mechanisms of clonal expansion, cellular competition, and genomic stability, we aim to identify key risk factors and develop strategies for preventing brain cancers. Through this work, we strive to advance brain health and reduce the societal impact of neurological diseases.

Creativity and curiosity-drive interdisciplinary research

A stylized figure of a person in a lab coat, wearing glasses, stands confidently with one hand in their pocket. They have brightly colored hair and a stethoscope around their neck. The background features various colorful question marks, suggesting themes of inquiry and curiosity in a medical context.

Our laboratory values individual perspectives in tackling scientific challenges, fostering a culture of collective creativity. We emphasize collaboration and open dialogue in a safe, judgment-free environment. We believe creativity thrives by combining personal experiences and knowledge, and it is enriched by drawing on the insights and expertise of others.   

My lab explores various aspects of brain mosaicism, driven by curiosity and creativity in an interdisciplinary approach. Here are two examples of our research directions:

Do cells risk damaging their DNA as they divide?

Image credit: Pei-Chi Wei

Our research focuses on understanding how DNA damage arises in neural stem cells and how this may contribute to brain disorders and cancers. Long genes, which control key neuronal functions like cell communication and plasticity, are especially prone to DNA damage. But why are these genes hotspots for such alterations?

We discovered specific regions in the DNA that frequently break, particularly in long genes essential for brain functions like communication and adaptability. These fragile regions become more vulnerable under stress during DNA duplication and are linked to neuropsychiatric disorders, cancers, and shared DNA changes in neurons originating from the same progenitors.

We found that these DNA breaks occur where copying DNA and reading its code collide. These areas lack the tools to repair stalled copying processes, making them especially prone to damage. Using advanced techniques, we showed that these breaks often align in ways that promote large deletions in critical genes.

We are investigating whether this DNA damage plays a role in diversifying the genomes of neural founder cells and whether deletions in critical genes contribute to tumor development.

How do neural stem cell clone sizes influence brain complexity?

Our research delves into how the size of neural stem cell clones impacts the brain’s structure and function. Neural stem clones are groups of neurons that share the same DNA blueprint, and their size directly influences the spatial organization and functional diversity of neurons in the brain. Intriguingly, studies show that the size of neuronal clones varies across brain regions, suggesting that clone size plays a key role in tailoring the brain’s architecture to its specific needs.

My lab develops preclinical tools and models to investigate clonal expansion, selection, and evolution in the developing brain. We focus on identifying the triggers of clonal competition—a process that can drive unregulated, excessive cell proliferation, also known as precancerous hyperproliferation. 

Our goal is to determine whether such unchecked proliferation in normal tissue increases the risk of cancer development. Ultimately, this research could uncover new risk factors and inform strategies for preventing brain cancer. 

Current team

  • A woman with long black hair smiles softly at the camera. She is wearing a light gray sleeveless top with lace detailing on one shoulder. The background is plain and white, highlighting her facial features and expression.

    Dr. Pei-Chi Wei

    Principal Investigator

  • Employee image

    Jana Berlanda

  • A smiling laboratory technician wearing a lab coat and gloves is seated at a workbench filled with various laboratory equipment and containers. The environment appears organized, with shelves lined with chemical reagents and tools used for scientific research.

    Lorenzo Corazzi

    Ph.D. student

  • A smiling woman wearing a lab coat and gloves stands in a laboratory. She has glasses and is near a workbench with various lab equipment and containers in the background. The atmosphere suggests a scientific research environment.

    Giulia Di Muzio

    Ph.D. student

  • Employee image

    Boyu Ding

  • A smiling man wearing glasses and a lab coat sits at a laboratory bench, surrounded by scientific equipment and instruments. He appears friendly and approachable, likely engaged in research or experimentation.

    Marco Giaisi

    Lab Manager

  • Employee image

    Dr. Alex Ing

  • Employee image

    Hsin-Jui Lu

Entire Team

Associated team members

Michael Allers
M.D. student with Prof. Dr. Dr. Peter Huber (E055)
E-mail: m.allers(at)dkfz-heidelberg.de
Phone: +49 6221 42 3249

 

Selected Publications

2025 - bioRxiv
2024 - Nature Communications
2024 - Nature
2020 - PNAS
2016 - Cell

Open Positions

We are looking for a pragmatic bioinformatic staff to advance research in development, DNA damage, tumorigenesis and cancer prevention via bulk NGS, single-cell and spatial-omics on culture ans preclinical models.

If you have a MSc (or PhD) in biology, biochemistry, neuroscience and turned computational science or vise versa, consider this oppertunity. We offer tailored professional growth, mentoring, and inclusive team atmosphere.

This call will close soon as we are receiving many applications fast. Don't want to missing out? Apply as soon as possible. https://jobs.dkfz.de/en/jobs/167686/data-scientist

 

Get in touch with us

A woman with long black hair smiles softly at the camera. She is wearing a light gray sleeveless top with lace detailing on one shoulder. The background is plain and white, highlighting her facial features and expression.

Dr. Pei-Chi Wei

Principal Investigator
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