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    Kotlarz Lab

    Decoding disease signatures of Pediatric IBD - A system biology-driven approach

    Prof. Dr. med. Daniel Kotlarz, PhD

    Professor for Precision Medicine of Pediatric IBD 

    ✉   daniel.kotlarz@med.uni-muenchen.de

    Heisenberg programme

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    Helmholtz Young Investigator Group

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    Research Topics

    • Genetic signatures in pediatric inflammatory bowel disease
    • Mucosal Immunology 
    • Preclinical Models of inflammatory bowel disease
    • Decoding disease signatures using a system biology-driven approach

    For information on our bioinformatic approaches, please visit our Helmholtz website:

    The mission of our research group is to explore the molecular causes in children with very early onset inflammatory bowel disease (VEO-IBD), a life-threatening condition. In particular, our laboratory focuses on decoding genetic and immune signatures of VEO-IBD by employing omics-based technologies and advanced preclinical models. We propose that our studies will lead to new insights into disease pathogenesis, diagnosis, and treatment for children with this intractable disease.


    Inflammatory bowel disease is a multifactorial disorder of the digestive tract triggered by environmental factors, immune dysfunctions, defective epithelial barrier function, and imbalances of the microbial flora in genetically susceptible individuals.

    About 20% of patients with IBD are diagnosed during childhood and adolescents. Children with very early onset inflammatory bowel diseases (VEO-IBD, age of onset <6 years) often show severe and life-threatening conditions refractory to conventional treatment.

    Paradigmatic studies by our laboratory have shown that VEO-IBD can be caused by monogenic IL-10R defects (Glocker et al, New Engl J Med 2009). Based on the knowledge of the underlying molecular etiology, IL-10R-deficient patients could be treated with allogeneic hematopoietic stem cell transplantation, an innovative therapeutic approach for defined patients with IBD (Kotlarz et al, Gastroenterology 2012). This prime example of translational research demonstrated the importance of genetic diagnostics for the clinical management of VEO-IBD patients and highlighted that rare variants of IBD represent exquisite models to identify key molecular factors controlling intestinal homeostasis.

    The overall goal of our laboratory is to explore the molecular pathomechanisms of VEO-IBD in order to develop novel diagnostic tools and therapies for children with intractable colitis.

    In collaboration with our partners in Boston (Dr. Scott Snapper) and Toronto (Dr. Aleixo Muise), we have established an international VEO-IBD consortium that will be supported by world experts in the field of immunology, genetics, genetic engineering, gastroenterology, intestinal stem cell biology, microbiomics and bioinformatics.

    To elucidate novel genetic signatures of VEO-IBD, we have established collaborations to more than 150 international clinical institutes and systematically screened one of the largest international cohorts of VEO-IBD by employing state-of-the-art next-generation sequencing. As proof-of-principle, our laboratory has characterized first VEO-IBD patients with TGFB1 (Kotlarz et al., Nat Genet 2018), CASP8 (Lehle et al., Gastroenterology 2019), and RIPK1 (Li et al., PNAS 2019) deficiency. Our computational analysis has also unraveled several novel candidate genes that might be implicated in the pathogenesis of VEO-IBD.

    We will analyze the molecular pathomechanisms of newly identified sequence variants by employing various experimental models (patient samples, heterologous model systems, mouse models) and state-of-the-art molecular and cell biological technologies.


    Despite advances in genome-wide sequencing, >75 % of VEO-IBD patients lack definitive genetic diagnosis. In addition, the disease mechanisms of most known genetic entities of VEO-IBD remain largely elusive and need to be further defined in order to develop personalized therapies.

    Intestinal inflammation is likely driven by alterations in tissue composition and cell-intrinsic cellular programs. In the past, transcriptomics studies have been hampered by analysis of bulk samples across entire tissues. We postulate that innovative single cell genomic analysis will allow comprehensive mapping of known and previously uncharacterized epithelial, stromal, and immune cell types as well as transcriptional disease states in complex intestinal tissues of VEO-IBD patients. Unbiased and multidimensional single cell transcriptomic data will facilitate the discovery of dysregulated inflammatory expression programs, thus providing critical insights into disease etiology and highlighting new therapeutic interventions.

    To dissect the molecular pathomechanisms of VEO-IBD, our laboratory has established an experimental platform to (i) conduct state-of-the-art assays on primary patients’ cells, (ii) patient-derived induced pluripotent stem cells and intestinal 3D mini guts (intestinal organoids), (iii) generate heterologous cellular models by genetic engineering (lentiviral gene transfer, CRISPR/Cas9), and (iv) analyze patient-derived humanized mouse models by cutting-edge cell biology, biochemical and immunological assays.

    Humanized Mouse Models

    Studies on primary patients’ cells are limited by access and knockout mouse models might have inherent limitations on extrapolating findings to human. Alternatively, humanized mice reconstituted with patient-derived cells are powerful tools for basic and applied human disease research. 

    Intestinal Organoids

    Intestinal organoid cell lines represent a cutting-edge 3D “mini-gut“-system with in vivo phenotypical characteristics allowing sophisticated studies on genetics, epigenetics, proteomics, and cell biology in intestinal epithelial cells from children with VEO-IBD.





    The overall goal of our research is to advance the understanding of key factors in IBD pathogenesis by employing omics-based technologies and preclinical disease models. This knowledge provides the groundwork for the development of personalized therapies in order to improve life quality for children suffering from life-threatening diseases.

    January 2026

    Congratulations, Xiang!

    Please join us in congratulating Xiang on a fantastic thesis defense! 

    December 2025

    New Doctor in Town! Congratulations, Jonas!

    Please join us in congratulating Dr. Bibus on a fantastic thesis defense! Important research, great presentation, and a very well-deserved title. Cheers to the new Doctor! 🎓🥂

    November 2025

    DEFINE consortium (TRR425) funded by DFG

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    November 2025

    LETSIMMUN awarded second funding period

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    July 2025

    David Illig receives FöFoLe Start-up grant

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    December 2024

    Daniel Kotlarz awarded prestigious Heisenberg Grant

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    May 2024

    Kotlarz Lab receives KRF Innovator Award

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    2023

    It is official: Dr. Li! 🎉

    Congratulations on successfully defending your PhD dissertation. It has been inspiring to witness your journey, hard work, and resilience. Excited to see all the great work you will do next!

    March 2022

    Cheers to the new Doctor! 

    Please join us in congratulating Dr. Illig on a fantastic thesis defense! Important research, great presentation, and a very well-deserved title. 

    May 2021

    CRC/TRR initiative LETSIMMUN funded by DFG

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    March 2021

    Kotlarz lab starts EKFS-funded key project 

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    March 2020

    Daniel Kotlarz awarded Heinz Maier-Leibnitz Preis

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    Jonas Bibus

    Jonas Bibus, PhD

    Post-Doc

    ✉ Jonas Bibus

    ☎ 089-4400-57985, Room: K0.02

    David Illig

    David Illig, PhD

    Post-Doc

    ✉ David Illig

    ☎ 089-4400-57985, Room: K0.02

    Daniel Kotlarz

    Dr. med. Daniel Kotlarz, PhD 

    Principal Investigator

    ✉ Daniel Kotlarz

    Room: K0.05

    Christopher Lance

    Christopher Lance, M.Sc. 

    Doctoral Researcher (PhD track)

    Co-advised with Prof. Dr. Fabian Theis

    ✉ Christopher Lance, Room: K0.25

    Xiang Shen

    Xiang Shen, M.Sc.

    Doctoral Researcher (PhD track)

    ✉ Xiang Shen

    Room: K0.13

    Jorge Vincentelli

    Jorge Vincentelli

    Doctoral Researcher (MD track)

    ✉ Jorge Vincentelli

    Room: K0.01

    Zhengyuan Xue

    Zhengyuan Xue, M.Sc. 

    Doctoral Researcher (PhD track)

    Co-advised with Prof. Dr. Dr. E. Zeggini & Dr. F. P. Casale 

    ✉ Zhengyuan Xue

    Room: K0.25

    Ziqi Yu

    Ziqi Yu

    Doctoral Researcher (PhD track)

    ✉ Ziqi Yu

    Room: K0.01

    Alina Hundt

    Alina Hundt

    Doctoral Researcher (MD track)

    ✉ Alina Hundt

    Room: K0.01

    Yuhan Jia

    Yuhan Jia

    Doctoral Researcher (PhD track)

    ✉ Jia Yuhan

    Waltherstraße 23

    Marina Kreuzeder

    Marina Kreuzeder, Dr. rer. nat.

    Scientific Project Manager

    ✉ Marina Kreuzeder

    ☎ 089-4400-57359, Room: K0.07

    Mina Pellegrini

    Mina Pellegrini, PhD

    Research assistant

    ✉ Mina Pellegrini

    ☎ 089-4400-57985, Room: K0.02

    Zeynep Ünal

    Zeynep Ünal, M.Sc. 

    Doctoral Researcher (PhD track)

    ✉ Zeynep Uenal

    Room: K0.01

    Benjamin Weinert

    Benjamin Weinert, M.Sc.

    Doctoral Researcher (PhD track)

    Co-advised by Prof. Dr. C. Marr

    ✉ Benjamin Weinert

    Helmholtz Institute

    Wing Yin Yeung

    Wing Yin Yeung, M.Sc. 

    Doctoral Researcher (PhD track)

    ✉ Wing Yeung

    Room: K0.01

    VEO-IBD Consortium Meeting Azores (2026)

    KRF Innovations Symposium Honolulu (2025)

    mitch@mitchtobias.com
    mitch@mitchtobias.com

    ECCO Berlin (2025)

    KRF Innovations Symposium San Francisco (2024)

    VEO-IBD Consortium Meeting Oxford (2024)

    Midwinter Conference Seefeld (2024)

    VEO-IBD Consortium Meeting Salzburg (2023)

    ECCO Copenhagen (2023)

    VEO-IBD Consortium Meeting Toronto (2022)

    IRTG1054 Retreat Venice (2022)

    “The Great Holiday Lab Quest!” 🔍✨ (2025)

    Scientific Retreat Munich (2025)

    Chinese Hotpot Christmas (2024)

    Retreat Salzburg (2024)

    Lab visit Aleixo Muise (2023)

    Retreat Nesselwang (2023)

    Retreat Regensburg (2022)

    Selected Publications


    Human MD2 deficiency - an inborn error of immunity with pleiotropic features. 

    Li Y, Yu Z, Schenk M, Lagovsky I, Illig D, Walz C, Rohlfs M, Conca R, Muise AM, Snapper SB, Uhlig HH, Garty BZ, Klein C, Kotlarz D (2023) J Allergy Clin Immunol 151, 791-796. 

    Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases.
    Li Y, Fuhrer M, Bahrami E, Socha P, Klaudel-Dreszler M, Bouzidi A, Liu Y, Lehle AS, Magg T, Hollizeck S, Rohlfs M, Conca R, Field M, Warner N, Mordechai S, Shteyer E, Turner D, Boukari R, Belbouab R, Walz C, Gaidt MM, Hornung V, Baumann B, Pannicke U, Al Idrissi E, Ali Alghamdi H, Sepulveda FE, Gil M, de Saint Basile G, Honig M, Koletzko S, Muise AM, Snapper SB, Schwarz K, Klein C, and Kotlarz D (2019). Proc Natl Acad Sci U S A 116, 970-975.

    Intestinal Inflammation and Dysregulated Immunity in Patients With Inherited Caspase-8 Deficiency.
    Lehle AS, Farin HF, Marquardt B, Michels BE, Magg T, Li Y, Liu Y, Ghalandary M, Lammens K, Hollizeck S, Rohlfs M, Hauck F, Conca R, Walz C, Weiss B, Lev A, Simon AJ, Gross O, Gaidt MM, Hornung V, Clevers H, Yazbeck N, Hanna-Wakim R, Shouval DS, Warner N, Somech R, Muise AM, Snapper SB, Bufler P, Koletzko S, Klein C, and Kotlarz D (2019). Gastroenterology 156, 275-278.

    Human TGF-beta1 deficiency causes severe inflammatory bowel disease and encephalopathy.
    Kotlarz D, Marquardt B, Baroy T, Lee WS, Konnikova L, Hollizeck S, Magg T, Lehle AS, Walz C, Borggraefe I, Hauck F, Bufler P, Conca R, Wall SM, Schumacher EM, Misceo D, Frengen E, Bentsen BS, Uhlig HH, Hopfner KP, Muise AM, Snapper SB, Stromme P, and Klein C (2018). Nat Genet 50, 344-348.

    Loss-of-function mutations in the IL-21 receptor gene cause a primary immunodeficiency syndrome.
    Kotlarz D, Zietara N, Uzel G, Weidemann T, Braun CJ, Diestelhorst J, Krawitz PM, Robinson PN, Hecht J, Puchalka J, Gertz EM, Schaffer AA, Lawrence MG, Kardava L, Pfeifer D, Baumann U, Pfister ED, Hanson EP, Schambach A, Jacobs R, Kreipe H, Moir S, Milner JD, Schwille P, Mundlos S, and Klein C (2013). J Exp Med 210, 433-443.

    Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy.
    Kotlarz D, Beier R, Murugan D, Diestelhorst J, Jensen O, Boztug K, Pfeifer D, Kreipe H, Pfister ED, Baumann U, Puchalka J, Bohne J, Egritas O, Dalgic B, Kolho KL, Sauerbrey A, Buderus S, Gungor T, Enninger A, Koda YK, Guariso G, Weiss B, Corbacioglu S, Socha P, Uslu N, Metin A, Wahbeh GT, Husain K, Ramadan D, Al-Herz W, Grimbacher B, Sauer M, Sykora KW, Koletzko S, and Klein C (2012). Gastroenterology 143, 347-355.

    Inflammatory bowel disease and mutations affecting the interleukin-10 receptor.
    Glocker EO, Kotlarz D, Boztug K, Gertz EM, Schaffer AA, Noyan F, Perro M, Diestelhorst J, Allroth A, Murugan D, Hatscher N, Pfeifer D, Sykora KW, Sauer M, Kreipe H, Lacher M, Nustede R, Woellner C, Baumann U, Salzer U, Koletzko S, Shah N, Segal AW, Sauerbrey A, Buderus S, Snapper SB, Grimbacher B, and Klein C (2009). N Engl J Med 361, 2033-2045.


    Please refer to the complete list of published work.


    We are looking constantly for motivated individuals to join our research group

    • undergraduate students (Bachelor / Master),
    • doctoral researchers
    • especially in the fields: Life Science and Bioinformatics

    If you are interested, please send your application (incl. CV, motivation letter and references) per e-mail to Daniel Kotlarz.

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    Kotlarz Lab


    Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital,

    Klinikum der Universität München, LMU München

    Postal Address:  

    Lindwurmstr. 4

    D-80337 Munich

    Germany

    Phone: +49 89 4400 57985

    Shipment of patient samples (please contact via Email prior to shipment):

    Dr. von Haunerschen Kinderspital

    Forschungszentrum KUBUS

    AG Klein

    Lindwurmstr. 2a

    D-80337 Munich

    Germany

    Phone: +49 (0)89 - 4400 - 57985

    Research at CCRC Hauner

    Contact LMU Klinikum

    Contact CCRC Hauner

    Haunersches

    CCRC Hauner - Comprehensive Childhood Research Center

    Kinderklinik und Kinderpoliklinik

    im Dr. von Haunerschen Kinderspital

    Ludwig Maximilians Universität München

    Lindwurmstr. 4

    80337 Munich, Germany


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