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.
Recent publications
Human organoids are superior to cell culture models for intestinal barrier research. Kollmann C, Buerkert H, Meir M, Richter K, Kretzschmar K, Flemming S, Kelm M, Germer CT, Otto C, Burkard N, Schlegel N. Front Cell Dev Biol. 2023 Oct 2;11:1223032. https://doi.org/10.3389/fcell.2023.1223032.
Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures. Yang ASP*, Dutta D*, Kretzschmar K*, Hendriks D*, Puschhof J, Hu H, Boonekamp KE, van Waardenburg Y, Chuva de Sousa Lopes SM, van Gemert GJ, de Wilt JHW, Bousema T, Clevers H, Sauerwein RW. Nat Commun. 2023 Aug 2;14(1):4631. https://doi.org/10.1038/s41467-023-40298-7. (*shared first authors)
Modelling adult stem cells and their niche in health and disease with epithelial organoids. Szabó L*, Seubert AC*, Kretzschmar K. Semin Cell Dev Biol. 2023 Jul 30;144:20-30. (*shared first authors). https://doi.org/10.1016/j.semcdb.2022.09.006.
Uncovering the mode of action of engineered T cells in patient cancer organoids. Dekkers JF, Alieva M, Cleven A, Keramati F, Wezenaar AKL, van Vliet EJ, Puschhof J, Brazda P, Johanna I, Meringa AD, Rebel HG, Buchholz MB, Barrera Román M, Zeeman AL, de Blank S, Fasci D, Geurts MH, Cornel AM, Driehuis E, Millen R, Straetemans T, Nicolasen MJT, Aarts-Riemens T, Ariese HCR, Johnson HR, van Ineveld RL, Karaiskaki F, Kopper O, Bar-Ephraim YE, Kretzschmar K, Eggermont AMM, Nierkens S, Wehrens EJ, Stunnenberg HG, Clevers H, Kuball J, Sebestyen Z, Rios AC. Nat Biotechnol. 2023 Jan;41(1):60-69. https://doi.org/10.1038/s41587-022-01397-w.
A Roadmap for the Human Oral and Craniofacial Cell Atlas. Caetano AJ, Human Cell Atlas Oral and Craniofacial Bionetwork, Sequeira I, Byrd KM. Journal of Dental Research. 2022 Oct; 101(11):1274-1288. https://doi.org/10.1177/00220345221110768.
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. https://doi.org/10.1016/j.stemcr.2021.07.007. (*shared first authors and #co-corresponding authors)
Generation and Characterization of Murine Oral Mucosal Organoid Cultures. Seubert AC, Krafft M, Kretzschmar K. J Vis Exp. 2021 Jul 31;(173). https://dx.doi.org/10.3791/62529.
Cancer research using organoid technology. Kretzschmar K. J Mol Med (Berl). 2021 Apr;99(4):501-515. https://doi.org/10.1007/s00109-020-01990-z.
Establishment of patient-derived cancer organoids for drug-screening applications. Driehuis E, Kretzschmar K#, Clevers H#. Nat Protoc. 2020 Oct;15(10):3380-3409. https://doi.org/10.1038/s41596-020-0379-4. (#co-corresponding authors)
Impressions of our research
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. He then joined the group of Prof. Hans Clevers at the Hubrecht Institute in Utrecht (NL). There he mapped cardiac regeneration on the single-cell level, developed new epithelial organoid models and discovered a new epidermal stem cell population marked by Troy/Tnfrsf19. Since 2020, Kai is a Junior Group Leader at the MSNZ Würzburg funded by the German Cancer Aid. In 2022, he received a prestigious European Research Council Starting Grant to fund his research and expand his research team.
Throughout his career, Kai has received multiple awards and honours among them the 2015 Nikon Young Scientist Award of the German Society for Cell Biology, long-term fellowships from HFSP and EMBO as well as a VENI talent award (ZonMW/NWO). Since 2023, Kai is further member of the Early Career Editorial Board of Stem Cell Reports, the scientific journal of the International Society for Stem Cell Research (ISSCR).
Alex Esteban Barroso
PhD Student
Alex received his bachelor's degree in Biotechnology from the Polytechnic University of Madrid and he completed his master's studies in the field of Immunology at the Complutense University of Madrid in 2022. In March 2023, he started his PhD in the Kretzschmar group.
Alex's PhD project is focused on deciphering oral mucosal tissue homeostasis and regeneration.
Alex's project is funded by the European Union/ERC.
Nadja Harnischfeger
PhD Student
After obtaining her bachelor's degree in biology, Nadja continued her studies in this field of science and specialised in pharmaceutical biology and molecular tumour biology during her master's studies at the University of Würzburg. In September 2022, she started her PhD in Kretzschmar group.
Nadja's PhD project is focused on patient-derived oral cancer organoids and their application for translational medicine.
Nadja's project is funded by the German Cancer Aid.
Sebastian John
MD Student
Sebastian studies medicine and Translational Medicine at the University of Würzburg. In October 2022, he joined the Kretzschmar group as medical doctoral student.
His project is focused on understanding the cellular and molecular mechanismens during the pathogenesis of oral chronic inflammation using single-cell transcriptomics and organoid technology.
Sebastian's project is funded by the Gradudate School of Life Sciences (GSLS) and the Single Cell Centre 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.
Marion is funded by the German Cancer Aid and the IZKF.
Max Lukman
M.Sc. Thesis Student
After obtaining a bachelor's degree in Biological Sciences in Xi'an Jiaotong-Liverpool University, Maxwell is now studying for a master's degree in Biochemistry at the University of Würzburg with a specialisation in Oncology. In January 2023, they joined the Kretzschmar group first as an internship student before staying for their master's thesis.
Maxwell's project is focussed on the plasticity of human oral mucosal fibroblasts.
Maxwell's project is funded by the German Cancer Aid.
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 PhD 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.
Anna's project is funded by the European Union/ERC.
Lili Szabo
PhD Student
Lili studied Biology at the Eötvös Lorand University in Budapest, where she performed 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 PhD 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.
Lili's project is funded by the German Cancer Aid.
You?
We are always looking for enthusiastic and highly motivated students (BSc or MSc level), doctoral students (PhD or MD) 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.
Funding
We are grateful for current and past funding from the German Cancer Aid, the European Research Council, the Graduate School of Life Sciences Würzburg, the IZKF Würzburg, the Single-Cell Center Würzburg, and the Foundation Tumor Research Head Neck.
You can find us here:
Institute for Virology and Immunobiology
MSNZ
Versbacher Str. 7
D-97078 Würzburg
