• Kai Kretzschmar, Ph.D.

    Adult Stem Cell Niches in Cancer

    Junior Group Leader at MSNZ Würzburg, Germany

  • ACADEMIC POSITIONS & EDUCATION

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    MSNZ, University Hospital Würzburg (DE)

    Junior Group Leader, Since January 2020

    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.

     

    My lab aims 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.

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    Hubrecht Institute, Utrecht (NL)

    Postdoctoral Fellow, June 2014 - DecemBer 2019

    I established tools to model the tumour microenvironment in colorectal cancer in vitro using epithelial organoid cultures in the laboratory of Professor Hans C. Clevers. I further studied epidermal stem cells and the regenerative capacity of the adult heart. I was supported by a VENI grant from the Netherlands Organisation of Scientific Research/NWO and long-term fellows of the Human Frontier Science Program/HFSP and the European Molecular Biology Organisation (EMBO).

     

    Activities & Outreach: Hubrecht Institute Postdoc Committee & Career Development Committee

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    University of Cambridge (UK)

    Doctor of Philosophy (Ph.D.) in Genetics, May 2014

    I studied epidermal stem cells and the interaction with their mesenchymal niche during homeostasis of adult skin under supervision of Professor Fiona M. Watt at her laboratories at the Cambridge Stem Cell Institute and KCL's Centre for Stem Cells & Regenerative Medicine.

     

    Activities & Outreach: Cambridge Science Festival, Wolfson Research Day, Open Academy Davos

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    Goethe University Frankfurt am Main (Germany)

    Degree (Diplom) in Biology, November 2009

    I did my final research project (Diplomarbeit) in Cell and Developmental Biology investigating gap junctional communication in skin.

     

    Activities & Outreach: Students' Parliament, Biology Students’ Council, Open Academy Davos

  • AWARDS, GRANTS & FELLOWSHIPS

    November 2022

    Selected member of the Early Career Editorial Board (ECEB) of Stem Cell Reports

    December 2021

    European Research Council (ERC) 2021 Starting Grant

    February 2019

    Grant to establish a Junior Research Group at the MSNZ Würzburg funded by the German Cancer Aid

    September 2018

    Young Investigator Award of the Fondation Leducq – Transatlantic Network of Excellence on Arrhythmogenic Cardiomyopathy

    June 2018

    International Society for Stem Cell Research (ISSCR) travel award

    September 2017

    Cardiovascular Research Netherlands (CVON)-HUSTCARE young talent program research grant

    June 2016-May 2018

    VENI grant from the Netherlands Organisation for Scientific Research (NWO)

    June 2015-December 2019

    Human Frontier Science Program (HFSP) long-term fellowship (non-stipendiary fellow: June 2016-May 2018)

    April 2015-December 2016

    European Molecular Biology Organization (EMBO) long-term fellowship (non-stipendiary fellow: June 2015-December 2016)

    March 2015

    Nikon Young Scientist of the German Society for Cell Biology (DGZ)

    June/July 2014

    Else Kröner Fresensius Foundation (EKFS) young scientist fellowship for the 64th Lindau Nobel Laureate Meeting

    June 2013

    British Society for Cell Biology (BSCB) travel award

    June 2013

    Wolfson College Cambridge travel award

    June 2012

    International Society for Stem Cell Research (ISSCR) travel award

    February 2012

    American Association for the Advancement of Science (AAAS)/Science Program for Excellence in Science award

    January 2010-December 2013

    Medical Research Council (MRC) UK Four-Year Ph.D. scholarship

    September 2007-August 2008

    Erasmus scholarship for exchange studies abroad

  • SELECTED PUBLICATIONS

    Please check PubMed for a complete and updated list of publications.

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    Development of Plasmodium falciparum liver-stages in hepatocytes derived from human fetal liver organoid cultures.

    NatURE CommunICATIONS. 2023 Aug 2;14(1):4631. doi: 10.1038/s41467-023-40298-7.

    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. (* = shared first authors)

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    Modelling adult stem cells and their niche in health and disease with epithelial organoids.

    SeminARS in Cell and Developmental Biology. 2023 Jul 30;144:20-30. doi: 10.1016/j.semcdb.2022.09.006. 

    Szabó L*, Seubert AC* & Kretzschmar K. (* = shared first authors)

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    Uncovering the mode of action of engineered T cells in patient cancer organoids.

    NatURE BiotechnolOGY. 2023 Jan;41(1):60-69. doi: 10.1038/s41587-022-01397-w.

    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.

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    Generation and Characterization of Murine Oral Mucosal Organoid Cultures​.

    J Vis Exp. 2021 Jul 31;(173). doi: 10.3791/62529.

    Seubert AC, Krafft M & Kretzschmar K.

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    Troy/Tnfrsf19 marks epidermal cells that govern interfollicular epidermal renewal and cornification​.

    Stem Cell Reports. 2021 Sep 14;16(9):2379-2394. doi: 10.1016/j.stemcr.2021.07.007.

    Kretzschmar K, Boonekamp KE, Bleijs M, Asra P, Koomen M, Chuva de Sousa Lopes SM, Giovannone B & Clevers H.

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    Cancer research using organoid technology.

    Journal of Molecular Medicine. 2021 APR;99(4):501-515. doi: 10.1007/s00109-020-01990-z.

    Kretzschmar K.

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    Single-cell derived tumor organoids display diversity in HLA class I peptide presentation.

    Nature Communications. 2020 OCT;11(1):5338. doi: 10.1038/s41467-020-19142-9.

    Demmers LC, Kretzschmar K, van Hoeck A, Bar-Ephraim 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.

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    Establishment of patient-derived cancer organoids for drug-screening applications​.

    Nature Protocols. 2020 Oct;15(10):3380-3409. doi: 10.1038/s41596-020-0379-4.

    Driehuis E, Kretzschmar K* & Clevers H*. (* = corresponding authors)

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    Organoids in immunological research.

    NatURE RevIEWS Immunology. 2020 May;20(5):279-293. doi: 10.1038/s41577-019-0248-y.

    Bar-Ephraim YE*, Kretzschmar K* & Clevers H. (* = shared first authors)

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    Long-term expansion and differentiation of adult murine epidermal stem cells in 3D organoid cultures.

    Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2019 JUL; 116(29):14630-14638. doi: 10.1073/pnas.1715272116.

    Boonekamp KE, Kretzschmar K, Wiener DJ, Asra P, Derakhshan S, Puschhof J, López-Iglesias C, Peters PJ, Basak O & Clevers H.

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    Identification of Enteroendocrine Regulators by Real-Time Single-Cell Differentiation Mapping.​

    Cell. 2019 Feb;176(5):1158-1173.e16. doi: 10.1016/j.cell.2018.12.029.

    Gehart H, van Es JH, Hamer K, Beumer J, Kretzschmar K, Dekkers JF, Rios A & Clevers H.

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    Profiling proliferative cells and their progeny in damaged murine hearts.

    Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2018. DOI: 10.1073/pnas.1805829115.

    Kretzschmar K*, Post P*, Bannier-Hélaouët M., Mattiotti A, Drost J, Basak O, Li VSW, van den Born M, Gunst QD, Versteeg D, Kooijman L, van der Elst S, van Es JH, van Rooij E, van den Hoff MJB and Clevers H. (* = shared first authors)

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    Wnt/β-catenin signaling in adult mammalian epithelial stem cells.

    Developmental Biology. 2017. doi: 10.1016/j.ydbio.2017.05.015.

    Kretzschmar K & Clevers H.

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    Wounding induces dedifferentiation of epidermal Gata6+ cells and acquisition of stem cell properties

    Nature Cell Biology. 2017 Jun;19(6):603-613. doi: 10.1038/ncb3532.

    Donati D, Rognoni E, Hiratsuka T, Liakath-Ali K, Hoste E, Kar G, Kayikci M, Russell R, Kretzschmar K, Mulder KW, Teichmann SA & Watt, FM.

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    Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research.

    Proceedings of the National Academy of Sciences of the United States of America (PNAS). 2016 Oct. doi: 10.1073/pnas.1614057113.

    Tetteh PW, Kretzschmar K, Begthel H, van den Born M, Korving J, Morsink F, Farin HF, van Es JH, Offerhaus GJA & Clevers H.

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    Organoids: modeling development and the stem cell niche in a dish.

    Developmental Cell. 2016 Sep 26;38(6):590-600. doi: 10.1016/j.devcel.2016.08.014

    Kretzschmar K & Clevers H.

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    Compartmentalized epidermal activation of β-catenin differentially affects lineage reprogramming and underlies tumor heterogeneity.

    Cell Reports. 2016 Jan 12;14(2):169-181. doi: 10.1016/j.celrep.2015.12.041

    Kretzschmar K, Weber C, Driskell RR, Calonje, E & Watt FM.

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    The androgen receptor antagonizes Wnt/β-catenin signaling in epidermal stem cells.

    Journal of Investigative Dermatology. 2015 Nov;135(11):2753-63. doi: 10.1038/jid.2015.242.

    Kretzschmar K, Cottle DL, Schweiger PJ & Watt FM.

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    BLIMP1 is required for postnatal epidermal homeostasis but does not define a sebaceous gland progenitor under steady-state conditions.

    Stem Cell Reports. 2014 Oct 14;3(4):620-33. doi: 10.1016/j.stemcr.2014.08.007.

    Kretzschmar K, Cottle DL, Donati G, Chiang MF, Quist SR, Gollnick HP, Natsuga K, Lin KI & Watt FM.

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    Markers of epidermal stem cell subpopulations in adult mammalian skin.

    Cold Spring Harbor Perspectives in Medicine. 2014 Jul 3;4(10). pii: a013631. doi: 10.1101/cshperspect.a013631. Review.

    Kretzschmar K & Watt FM.

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    Distinct fibroblast lineages determine dermal architecture in skin development and repair.

    Nature. 2013 Dec 12;504(7479):277-81. doi: 10.1038/nature12783.

    Driskell RR, Lichtenberger BM*, Hoste E*, Kretzschmar K*, Simons BD, Charalambous M, Ferron SR, Herault Y, Pavlovic G, Ferguson-Smith AC & Watt FM. (* = shared second authors)

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    Lineage tracing.

    Cell. 2012 Jan 20;148(1-2):33-45. doi: 10.1016/j.cell.2012.01.002.

    Kretzschmar K & Watt FM.

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    Reprogramming adult dermis to a neonatal state through epidermal activation of β-catenin.

    Development. 2011 Dec; 138(23):5189-99. doi: 10.1242/dev.064592.

    Collins CA, Kretzschmar K & Watt FM.

  • FIND ME ON

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    WWW

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    ResearchGate

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  • IMPRESSUM/CONTACT

    This is a personal website that is independent from the official websites of the University Hospital Würzburg and MSNZ Würzburg.

    Dr. Kai Kretzschmar
    Universitätsklinikum Würzburg
    IZKF/MSNZ Würzburg
    Josef-Schneider-Str. 2
    97080 Würzburg (Germany)
    +49 (0)931 31-88085