Kretzschmar Group
Adult Stem Cell Niches in Cancer
Adult stem cells–the cells that maintain and regenerate the tissues in our body–reside in a specialised microenvironment termed the stem cell niche. While stem cell niches are tissue-specific, two cellular components–fibroblasts and immune cells–have surfaced as prominent niche members across the body. Stem cells take cues from their microenvironment to control smooth transition between several plastic states, which are critical to maintain tissue homoeostasis and to regenerate in response to injury. Conversely, in diseases such as cancer, aberrant (stem) cells can acquire the ability to remodel their microenvironment allowing for the progression of disease.
We aim to decipher the crosstalk between stem/tumour cells and their microenvironment using the epithelia of the head and neck region as model system. To unravel the fundamental mechanisms underlying tissue homeostasis and tumourigenesis, we apply organoid technology, immune/stromal cell–organoid co-cultures, 3D whole-mount imaging and advanced transcriptomics and use both mouse models and patient material. It is our ultimate goal to exploit this communication to improve therapeutic treatments of head and neck cancer patients.
We are grateful for research funding from the German Cancer Aid, the Interdisciplinary Centre for Clinical Research and the Foundation Tumor Research Head Neck.
Recent publications
Troy/Tnfrsf19 marks epidermal cells that govern interfollicular epidermal renewal and cornification. Kretzschmar K*,#, Boonekamp KE*, Bleijs M, Asra P, Koomen M, Chuva de Sousa Lopes SM, Giovannone B, Clevers H#. Stem Cell Reports. 2021 Sep 14;16(9):2379-2394. doi: 10.1016/j.stemcr.2021.07.007. (*shared first authors and #co-corresponding authors) https://doi.org/10.1016/j.stemcr.2021.07.007
Generation and Characterization of Murine Oral Mucosal Organoid Cultures. Seubert AC, Krafft M, Kretzschmar K. J Vis Exp. 2021 Jul 31;(173). doi: 10.3791/62529. https://dx.doi.org/10.3791/62529
Cancer research using organoid technology. Kretzschmar K. J Mol Med (Berl). 2021 Apr;99(4):501-515. doi: 10.1007/s00109-020-01990-z. https://doi.org/10.1007/s00109-020-01990-z
Single-cell derived tumor organoids display diversity in HLA class I peptide presentation. Demmers LC, Kretzschmar K, Van Hoeck A, Bar-Epraïm YE, van den Toorn HWP, Koomen M, van Son G, van Gorp J, Pronk A, Smakman N, Cuppen E, Clevers H, Heck AJR, Wu W.Nat Commun. 2020 Oct 21;11(1):5338. doi: 10.1038/s41467-020-19142-9. https://doi.org/10.1038/s41467-020-19142-9
Establishment of patient-derived cancer organoids for drug-screening applications. Driehuis E, Kretzschmar K#, Clevers H#. Nat Protoc. 2020 Oct;15(10):3380-3409. doi: 10.1038/s41596-020-0379-4. (#co-corresponding authors) https://doi.org/10.1038/s41596-020-0379-4
Organoids in immunological research. Bar-Ephraim YE*, Kretzschmar K*, Clevers H. Nat Rev Immunol. 2020 May;20(5):279-293. doi: 10.1038/s41577-019-0248-y. (*shared first authors) https://doi.org/10.1038/s41577-019-0248-y
Kai Kretzschmar
Junior Group Leader
Kai studied biology at Goethe-University Frankfurt am Main (DE) and received his PhD degree in genetics from the University of Cambridge (UK) in 2014. During his PhD research with Prof. Fiona M. Watt, Kai investigated epidermal stem cells and their niche during tissue homeostasis, regeneration and tumourigenesis. He then joined the group of Prof. Hans Clevers at the Hubrecht Institute in Utrecht (NL). There he mapped the proliferative responses of adult hearts during regeneration on the single-cell level, developed epithelial organoid models for skin epidermis and immuno-oncology and defined Troy/Tnfrsf19 as a new marker of a population of epidermal stem cells. Since 2020, Kai is a Junior Group Leader at the MSNZ Würzburg.
Marion Krafft
Technician
Marion finished her MTLA training at the University of Würzburg in 2018. Since October 2020 she is working at the MSNZ in the groups of Dr Kai Kretzschmar and Dr Angela Riedel.
Her laboratory skills include different cell culture techniques (cell lines and organoid cultures) as well as various RNA and DNA based methods, immunohistochemistry, flow cytometry and mouse experiments. In addition she is responsible for the lab organization in general.
Anna Seubert
PhD Student
Anna studied biochemistry at the University of Würzburg and since September 2020, she is a PhD student in the Kretzschmar group.
Anna’s project is focussed on the homeostasis of the oral mucosa and the processes underlying tumour formation. To gain further insights, she is using 3D whole-mount imaging, organoid technology and advanced transcriptomics.
Lili Szabo
PhD Student
Lili studied Biology at the Eötvös Lorand University in Budapest, where she absolved her Master project on characterization the role of extracellular proteins in the tumour microenvironment. Since September 2020, she is a PhD student in the Kretzschmar group.
Lili’s project is focussed on the crosstalk between tumour cells and their cellular microenvironment in head and neck cancer. To better understand this cell–cell communication, she is applying innovative methods such as organoid technology, immune/stromal cell–organoid co-cultures and single-cell transcriptomics.
You?
We are always looking for enthusiastic and highly motivated students (BSc or MSc level), PhD students and postdocs. Should you have a particular interest in our research field, please get in touch with Dr Kretzschmar to discuss possible opportunities.
A must read for students planning to apply for a position in the lab: How to Pick a Graduate Advisor.
Alumni
Vivien Reinecke (MSc student, 2020–2021)
Nina Dehnert (MSc student, summer 2021)
Shivani Rajhansa (BSc student, summer 2021)
You can find us here:
Institute for Virology and Immunobiology
MSNZ
Versbacher Str. 7
97078 Würzburg
