Maria Genander

Maria Genander

Principal Researcher | Docent
Visiting address: Solnavägen 9, 17165 Stockholm
Postal address: C5 Cell- och molekylärbiologi, C5 CMB Genander, 171 77 Stockholm
Part of:

About me

  • Our research aims to identify regulatory mechanisms that guide epithelial stem cells in forming and maintaining functional tissue architecture, and how deregulation of these processes leads to disease.

    We are also found here:
    https://ki.se/en/cmb/maria-genanders-group

Research

  • The Genander lab investigates the mechanisms of stem cell maintenance, lineage specification, and differentiation during epithelial development, homeostasis, and disease. We explore the cellular complexity of the skin and dissect the seemingly uniform esophageal epithelium to identify stem cell heterogeneity, uncover region-specific stem cell behaviors, and elucidate the molecular pathways that govern tissue architecture and function.

    Current Projects

    Understanding mechanisms of epithelial regionalization – location matters.

    We have characterized the cellular landscape and transcriptional signatures along the esophageal tube, revealing how local stem cell–niche architectures dictate stem cell behavior in vivo. Our current focus is on understanding how these regional differences influence epithelial regeneration and tumor initiation. We aim to map local cell–cell communication circuits and identify signaling pathways that are differentially engaged within specific epithelial regions. Ultimately, our goal is to uncover pro-regenerative or tumor-suppressive mechanisms that may be relevant to human epithelial diseases.

    Citrullination – investigating posttranslational protein modifications in regeneration

    Citrullination, a post-translational modification of proteins, has been implicated in both stem cell renewal and various disease processes. Our research focuses on elucidating the role of citrullination in regulating stem cell maintenance and lineage commitment during the dynamic process of hair follicle regeneration.

    Current Lab Members:


    Evelien Eenjes, Research Specialist
    Wei Yang, Research Specialist
    Li Lei, Post Doc

    Kylie Hin-Man Mak, PhD student

    Jesse Kuipers, Research Assistant


    Interested in joining the lab?

    We are looking for highly motivated PhD or postdoctoral candidates who are interested in epithelial stem cell biology. Contact Maria Genander directly to get in touch!

Articles

All other publications

Grants

  • Swedish Research Council
    1 January 2024 - 31 December 2026
    In many stem cell niches, stem cells are tucked away in anatomically distinct locations, enabling exclusive interactions with niche signals that maintain stemness and prevent differentiation. In structurally simple epithelia such as the esophagus, no local stem cell niches have yet been identified. In line with the apparent lack of local esophageal microenvironments, a single progenitor cell population is suggested to maintain the epithelia during homeostasis and to be the cell-of-origin in squamous cell carcinomas. We have, for the first time, identified functional heterogeneity within the esophageal progenitor population linked to a proximal-distal signaling gradient. Furthermore, we have identified enrichment of renewing progenitor cells in specialized distal micro-niches associated with folding of the epithelial sheet. Here we exploit quantitative in vivo lineage tracing followed by mathematical modelling, single cell/nuclei sequencing, spatial transcriptomics and organoid co-cultures in mouse and human esophagi to identify and functionally characterize how local signaling environments (stem cell niches) influence progenitor fate normally and upon regenerative or transformative challenges.
  • Swedish Cancer Society
    1 January 2023
    Up to 90% of all cancers arise in epithelial tissues such as the esophagus. Tumors arise due to mutations in the stem cells that normally divide to generate new specialized tissue cells. Cancer is thus not only formed from stem cells, but also uses similar processes as normal stem cells to form a tumor. We believe that it is of the utmost importance to map normal stem cells and the signals required for normal tissue function in order to fully understand, and eventually treat, cancer. The esophagus has long been considered a simple channel that transports food from the mouth to the stomach. However, our research indicates that there are large local differences between and within the cell types found along the esophagus. This in turn creates regional variations in the signals that affect the esophageal stem cells. We want to identify these signals and understand how local environments affect the esophagus' ability to heal in case of injury and respond to harmful mutations. The incidence of cancer is unevenly distributed along the esophagus, indicating that regional differences may influence tumorigenesis in humans. We use both mouse models, 3D organoids and human material to characterize and functionally understand how stem cells in the esophagus are affected by their immediate environment. Understanding these local environments is a relevant clinical question that will lead to greater understanding of the mechanisms underlying tumorigenesis in the esophagus, with the hope of future new treatment strategies.
  • European Research Council
    1 March 2020 - 31 August 2026
    Cancer develops from mutations in stem and progenitor cells. Patients suffering from esophageal squamous cell carcinoma are commonly treated by a combination of chemotherapy and esophagectomy, a debilitating surgical procedure. My group have identified heterogeneity within the esophageal progenitor population in homeostasis which is likely to have implications for the development of squamous cell carcinomas of the esophagus, lead to targeted therapeutic strategies and hopefully reduce the need for surgical intervention. Stem and progenitor cells reside in a complex microenvironment, or niche, that is instructive in determining cell fate during homeostasis and tumor initiation. In the morphologically uniform esophageal epithelium, the presence of progenitor subpopulations cells as well as local microenvironmental niches is not evident. My group aim to not only delineate the functional heterogeneity within the esophageal progenitor population during homeostasis and cancer development, but also map out and eventually target the stromal niche cells driving this phenotypic epithelial heterogeneity. Furthermore, we will use a clinically relevant platform to screen for druggable targets with the ability to eliminate esophageal tumor initiating cells. The incidence of human esophageal squamous cell carcinomas is dramatically increasing, and delineation of the esophageal stem cell niche is a vital first step towards identifying new combined therapeutic strategies directed at eliminating this cancer.
  • Swedish Cancer Society
    1 January 2020
    The formation of a tumor takes place with the help of processes similar to those required to form new tissues during the development of an organism. A tissue consists of a number of cell types with specific functions which are formed from stem cells. Analogous to the stem cells found in normal tissues, in (disc) epithelial cancer there is a group of cells that have the ability to regenerate an entire tumor. These cells are called tumor-initiating cells, or cancer stem cells. Cancer stem cells can not only arise through mutations in normal stem cells, but they also use processes established by normal stem cells during tissue development. This project has several parts that all aim to understand how stem cells in healthy skin and esophagus work to be able to understand the origin of squamous cell carcinoma in these tissues. We will study proteins found in normal skin stem cells as well as cancer stem cells in squamous cell carcinoma. We believe that detailed knowledge of these proteins can lead to an understanding of how cancer develops in the skin. In addition to this, we will characterize functional differences between stem cells in the esophagus. We believe that these differences are important for maintaining a functioning esophagus, and that some of the normal stem cells can give rise to esophageal cancer. The aim of this research is to increase our understanding of the mechanisms used by normal stem cells to generate specialized tissue cells, as well as how these mechanisms are utilized or altered in cancer stem cells. We also want to map differences within seemingly similar normal stem cells in order to better understand how cancer can occur. The ultimate goal is to be able to define new and better treatment strategies for patients with squamous cell carcinoma.
  • Comparative studies of stem and tumor cells in skin
    Ragnar Söderberg Foundation
    1 January 2016 - 31 December 2020
  • Mechanisms of skin self-renewal, differentiation and cancer
    Swedish Foundation for Strategic Research
    1 September 2015 - 30 April 2018

Employments

  • Principal Researcher, Department of Cell and Molecular Biology, Karolinska Institutet, 2022-

Degrees and Education

  • Docent, Karolinska Institutet, 2025
  • Degree Of Doctor Of Philosophy, Department of Cell and Molecular Biology, Karolinska Institutet, 2009

News from KI

Events from KI