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Research Labs
Klein Lab

Klein Lab

Research topics

Neutrophil Granulocytes
Primary Immunodeficiency Disorders
Gene Therapy

Prof. Christoph Klein

✉ christoph.klein@med.uni-muenchen.de

☎ +49-89-4400-57701

Assistant

✉ kinderklinik.direktionssekretariat@med.uni-muenchen.de

☎ +49-89-4400-57701

Our mission is to understand the basic principles of the blood and immune system by studying children with rare inherited disorders. Starting with the analysis of the patients’ phenotype, we unravel the genetic etiology of rare diseases using a variety of in vitro and in vivo models. We aim to develop novel therapeutic strategies with a particular focus on cell and gene therapy.

Image without a title — Subcellular localization of genetic defects associated with severe congenital neutropenia (modified from Boztug and Klein, 2011)

Severe congenital neutropenia (SCN) is a rare heterogeneous genetic disorder caused by abnormal myeloid differentiation and susceptibility to severe bacterial or fungal infections. Several disease-causing genetic defects have been identified (e.g. ELANE, HAX1, G6PC3, GCSFR, JAGN1, VPS45, SMARCD2, SRP54). Despite this progress, the molecular etiology in many patients with neutrophil disorders as well as the epistatic relationships remain enigmatic.

Our research is directed towards identification of hitherto unknown genetic defects and towards a systems-biology approach to define principles that orchestrate differentiation and function of neutrophil granulocytes. We make use of induced pluripotent stem cells in combination with CRISPR-Cas-based genome editing technology as well as cell biological and multi-omics analysis to address specific questions.

Inborn errors of immunity (IEI) are rare genetic diseases of the immune system, characterized by immunodeficiency, autoimmunity, autoinflammation, or predisposition to cancer. With our dynamic team of clinicians, bioinformaticians and lab-based biologists, we aim to explore PIDs and identify their underlying genetic cause(s). Through clinical and molecular investigation of IEIs, we and other groups have been able to greatly advance our understanding of the cell biology and biochemistry orchestrating the proper functioning of the immune system.

A key step in understanding PIDs is whole genome sequencing (WGS) of patients’ genomic DNA and state-of-the-art computational analysis. However, given the enormous genetic variability between individuals, such an analysis typically generates a number of potential gene candidates that must then be further investigated to assess their potential biological relevance and functional consequence(s). This is achieved through state of the art in vitro and in vivo laboratory based studies, specifically tailored for the gene of interest and the patient disease and phenotype. This factor demands from our researchers a substantial level of versatility, presenting them with a unique challenge and opportunity to continually adapt, update and enhance their skills. Ultimately, utilizing our worldwide network of collaborators, we aim to find additional patients with similar phenotypes and genotypes.

Our established and growing patient databases are key for these projects. By virtue of large international networks such as the Care-for-Rare Alliance and the Very-Early-Onset Inflammatory Bowel Disease Consortium we are in the privileged position to reach important milestones and to continuously expand our projects. We have successfully identified a number of novel genes associated with inherited defects of cells of the innate and adaptive immune system, adding to our understanding of these diseases and approaches available for their treatment. Our work now continues to identify new immune pathologies, their underlying genetic and biology, and improvements in the manner in which they are treated.

Publications:

Abdollahpour H, Appaswamy G, Kotlarz D, Diestelhorst J, Beier R, Schaffer AA, Gertz EM, Schambach A, Kreipe HH, Pfeifer D, Engelhardt KR, Rezaei N, Grimbacher B, Lohrmann S, Sherkat R, Klein C (2012) The phenotype of human STK4 deficiency. Blood 119: 3450-3457. PubMed

Bahrami E, Witzel M, Racek T, Puchalka J, Hollizeck S, Greif-Kohistani N, Kotlarz D, Horny HP, Feederle R, Schmidt H, Sherkat R, Steinemann D, Gohring G, Schlegelbeger B, Albert MH, Al-Herz W, Klein C (2017) Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations. The Journal of allergy and clinical immunology. PubMed

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

Schober T, Magg T, Laschinger M, Rohlfs M, Linhares ND, Puchalka J, Weisser T, Fehlner K, Mautner J, Walz C, Hussein K, Jaeger G, Kammer B, Schmid I, Bahia M, Pena SD, Behrends U, Belohradsky BH, Klein C, Hauck F (2017) A human immunodeficiency syndrome caused by mutations in CARMIL2. Nature communications 8: 14209. PubMed

Li Y, Führer 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, Hönig M, Koletzko S, Muise AM, Snapper SB, Schwarz K, Klein C, Kotlarz D (2019).Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. PNAS 15;116(3):970-975. Pubmed

Gene therapy has emerged as a new paradigm of targeted and personalized treatment severe inborn errors of immunity, including the Wiskott Aldrich Syndrome (WAS). WAS is a complex life-threatening PID characterized by recurrent pyogenic, viral and fungal infections, thrombocytopenia and autoimmunity. It is an X-linked disorder caused by loss of function mutations in the gene encoding the Wiskott-Aldrich syndrome protein (WASP). WASP-deficiency leads to multiple dysfunctions in different subgroups of leukocytes, including defective T and B cell function, disturbed formation of the NK cell immunological synapse and impaired migratory responses in all leukocyte subgroups.

In 2004, we initiated a hematopoietic stem cell gene therapy trial using a γ-retroviral vector to reconstitute WASP expression. Ten patients with severe WAS were enrolled. 9 out of ten patients showed sustained engraftment and correction of WASP expression in lymphoid and myeloid cells and platelets as well as resolution of immunodeficiency, autoimmunity, and bleeding diathesis. Several years after gene therapy however, patients developed clonal hematopoietic disorders such as myelodysplastic syndromes and acute leukemias as a consequence of insertional mutagenesis. Our study showed hematopoietic stem cell gene therapy for WAS is feasible and effective, but the use of γ-vectors is associated with a substantial risk of leukemogenesis. We now hypothesize that WAS is associated with decreased genomic stability and continue to work on the development of both efficacious and safe techniques for the genetic engineering of HSC, to cure WAS and other primary immunodeficiency diseases. We make use of novel large animal models and CRISPR-Cas9-mediated gene editing to secure physiological gene expression and to minimize unwanted side-effects.

Publications:

Boztug K, Dewey RA, Klein C (2006) Development of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome. Curr Opin Mol Ther 8: 390-395. PubMed

Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Diez IA, Dewey RA, Bohm M, Nowrouzi A, Ball CR, Glimm H, Naundorf S, Kuhlcke K, Blasczyk R, Kondratenko I, Marodi L, Orange JS, von Kalle C, Klein C (2010) Stem-cell gene therapy for the Wiskott-Aldrich syndrome. The New England journal of medicine 363: 1918-1927. PubMed

Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M, Modlich U, Beier R, Gohring G, Steinemann D, Fronza R, Ball CR, Haemmerle R, Naundorf S, Kuhlcke K, Rose M, Fraser C, Mathias L, Ferrari R, Abboud MR, Al-Herz W, Kondratenko I, Marodi L, Glimm H, Schlegelberger B, Schambach A, Albert MH, Schmidt M, von Kalle C, Klein C (2014) Gene therapy for Wiskott-Aldrich syndrome--long-term efficacy and genotoxicity. Science translational medicine 6: 227ra233. PubMed

Jeyapoorani Balasuburamanian

Genomic Scientist

✉ Jeyapoorani.Balasuburamanian@med.uni-muenchen.de

Elisabeth Brandl, M.Sc.

Bioinformatician

✉ elisabeth.brandl@med.uni-muenchen.de

Waltherstr. 23, 3rd floor

Raffaele Conca

Manager FACS Facility and Technician

✉ raffaele.conca@med.uni-muenchen.de

☎ 089-4400-74994, Room K0.24

Yanxin Fan, PhD

Postdoctoral Researcher

✉ yanxin.fan@med.uni-muenchen.de

☎ 089-4400-57980

Isabel Gök, M.Sc.

Scientific Assistent

✉ Isabel.Goek@med.uni-muenchen.de

Gabriele Heilig

MTLA/Technician

✉ Gaby.Heilig@med.uni-muenchen.de

☎ 089-4400-53170, Room: K0.19

Martina Kalauz

Technician

✉ martina.kalauz@med.uni-muenchen.de

☎ 089-4400-57488, Room KU.10

Prof. Dr. Christoph Klein

Prinicipal Investigator

✉ christoph.klein@med.uni-muenchen.de

☎ 089-4400-57701, Room: A3.05

Julia Krebs

MTA

✉ Julia.Krebs@med.uni-muenchen.de

Dr. med. Robert Lersch

Clinician Scientist

✉ Robert.Lersch@med.uni-muenchen.de

☎ 089-4400-54724, Room: K0.31

Mai Khanh Mai

Bioinformatician

✉ Mai.Mai@med.uni-muenchen.de

Heidi Noll-Puchta, VTA

Technician & Lab Manager

✉ Heidi.Noll-Puchta@med.uni-muenchen.de

☎ 089-4400-54724

Room: K0.31

Daniel Petersheim

Postdoctoral Researcher

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

☎ 089-4400-57985, Room: K0.01

Christopher Radtke

Doctoral Researcher (MD)

✉ christopher.radtke@med.uni-muenchen.de

Room: K0.01

Sebastian Sigl

Doctoral Researcher

✉ Sebastian.Sigl@med.uni-muenchen.de

☎ 089-4400-57985, Room: K0.03

Regina Steck, PhD

Scientific Project Manager

✉ regina.steck@med.uni-muenchen.de

☎ 089-4400-57977, Room: K0.07

Maria Watzlowik, PhD

Scientific Project Manager

✉ maria.watzlowik@med.uni-muenchen.de

☎ 089-4400-85997, Room: K0.07/A3.03

Andreas Wölfle

Fachinformatiker

✉ Andreas.Woelfle@med.uni-muenchen.de

Waltherstr. 23, 3rd floor

Daniel Bergér

Doctoral Researcher (PhD track)

✉ daniel.berger@med.uni-muenchen.de

☎ 089-2180-76861, Gene Center, LMU, Feodor-Lynen-Str. 25, A2.65

Pin-Hsuan Chen

Doctoral Researcher (PhD track)

✉ pinshuan.chen@med.uni-muenchen.de

☎ 089-4400-57974, Room K0.13

Irene da Cruz, PhD

Bioinformatician

✉ irene.da@med.uni-muenchen.de

Waltherstr. 23, 3rd floor

Dr. med. Stephanie Frenz-Wießner, PhD

Clinician Scientist

✉ stephanie.frenz@med.uni-muenchen.de

☎ 089-4400-57985, currently UCLA

Julian Jungnitz

Bioinformatician

✉ julian.jungnitz@med.uni-muenchen.de

Mehmet Kiziltug

Doctoral Researcher (Phd)

✉ Mehmet.Kiziltug@med.uni-muenchen.de

☎ 089-4400-57974, Room: K0.13

Anna Kolz, PhD

Scientific Project Manager

Parental Leave

✉ anna.kolz@med.uni-muenchen.de

☎ 089-4400-57981, Room A3.03

Monika Linder, PhD

stv. Laborleitung

✉ monika.linder@med.uni-muenchen.de

☎ 089-4400-57704, Room K0.03

Chaochen Lu, PhD

Postdoctoral Researcher

✉ chaochen.lu@med.uni-muenchen.de

☎ 089-2180-76861, Gene Center, LMU, Room: A.2.65

Larissa Mantoan

Doctoral Researcher (PhD)

✉ larissa.mantoan@med.uni-muenchen.de

☎ 089-4400-57935, Room: K0.03

Megha Mukherjee

Doctoral Researcher (PhD)

✉ megha.mukherjee@med.uni-muenchen.de

☎ 089-4400-57985, Room: K0.01

Henrik Otterstedt

Bioinformatician, Doctoral researcher (PhD)

✉ Henrik.otterstedt@med.uni-muenchen.de

Isabel Plonner

Technician

✉ isabel.plonner@med.uni-muenchen.de

☎ 089-4400-57780, Room: KU.10

Meino Rohlfs, PhD

NGS Facility Manager & Postdoctoral Researcher

✉ meino.rohlfs@med.uni-muenchen.de

☎ 089-4400-57780, Room: KU.08

Chonlatis Srichumpuang, MD

Doctoral Researcher (PhD)

✉ Chonlatis.Srichumpuang@med.uni-muenchen.de

Anne Stolz, PhD

Postdoctoral Researcher

✉ anne.stolz@med.uni-muenchen.de

Room: K0.03

Daniel Weiß

Bioinformatician

✉ daniel.weiss@med.uni-muenchen.de

☎ 089-4400-57451, Waltherstr. 23, 3rd floor

Selected Publications:

Frenz-Wiessner S, Fairley SD, Buser M, Goek I, Salewskij K, Jonsson G, Illig D, Zu Putlitz B, Petersheim D, Li Y, Chen PH, Kalauz M, Conca R, Sterr M, Geuder J, Mizoguchi Y, Megens RTA, Linder MI, Kotlarz D, Rudelius M, Penninger JM, Marr C, Klein C. (2024) Generation of complex bone marrow organoids from human induced pluripotent stem cells. Nat Methods. 21(5):868-881.

Danhauser K, Mantoan LDL, Dittmer JM, Leutner S, Endres S, Strniscak K, Pfropfreis J, Bialke M, Stahl D, Frey BA, Gläser SS, Ritter LA, Linhardt F, Maag B, Miebach GDE, Schäfer M, Klein C, Hinske LC. (2024) On-site electronic consent in pediatrics using generic Informed Consent Service (gICS): Creating a specialized setup and collecting consent data. PLOS Digit Health. 3(11):e0000661.

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) Human MD2 deficiency-an inborn error of immunity with pleiotropic features. J Allergy Clin Immunol. 151(3):791-796.e7.

Linder MI, Mizoguchi Y, Hesse S, Csaba G, Tatematsu M, Łyszkiewicz M, Ziȩtara N, Jeske T, Hastreiter M, Rohlfs M, Liu Y, Grabowski P, Ahomaa K, Maier-Begandt D, Schwestka M, Pazhakh V, Isiaku AI, Briones Miranda B, Blombery P, Saito MK, Rusha E, Alizadeh Z, Pourpak Z, Kobayashi M, Rezaei N, Unal E, Hauck F, Drukker M, Walzog B, Rappsilber J, Zimmer R, Lieschke GJ, Klein C. (2023) Human genetic defects in SRP19 and SRPRA cause severe congenital neutropenia with distinctive proteome changes. Blood. 141(6):645-658.

Aminorroaya A, Rayzan E, Shahkarami S, Seyedpour S, Zoghi S, Aryan Z, Somekh I, Rohlfs M, Klein C, Esmaeilzadeh H, Rezaei N. (2023) Novel DNMT3B Mutation in a Patient with Immunodeficiency, Centromeric Instability, and Facial Anomalies (ICF) Syndrome and a Bronchopulmonary Collateral Artery. Endocr Metab Immune Disord Drug Targets. 23(3):410-415.

Fan Y, Murgia M, Linder MI, Mizoguchi Y, Wang C, Łyszkiewicz M, Ziȩtara N, Liu Y, Frenz S, Sciuccati G, Partida-Gaytan A, Alizadeh Z, Rezaei N, Rehling P, Dennerlein S, Mann M, Klein C. (2022) HAX1-dependent control of mitochondrial proteostasis governs neutrophil granulocyte differentiation. J Clin Invest. 132(9):e153153.

Momtazmanesh S, Rayzan E, Zoghi S, Shahkarami S, Molatefi R, Mohammadzadeh I, Ghaffari J, Mahmoudi H, Dmytrus J, Segarra-Roca A, Somekh I, Witzel M, Hauck F, Boztug K, Klein C, Rezaei N. (2021) Novel Variants of DOCK8 Deficiency in a Case Series of Iranian Patients. Endocr Metab Immune Disord Drug Targets. 2021 Feb 26.

Maroufi SF, Shaka Z, Mojtabavi H, Sadeghalvad M, Rayzan E, Sedighi I, Shahkarami S, Najafi M, Rohlfs M, Klein C, Rezaei N. (2021) Novel G6PC3 Mutations in Patients with Congenital Neutropenia: Case Reports and Review of the Literature. Endocr Metab Immune Disord Drug Targets. 2021;21(9):1660-1668.

Frey L, Ziętara N, Łyszkiewicz M, Marquardt B, Mizoguchi Y, Linder MI, Liu Y, Giesert F, Wurst W, Dahlhoff M, Schneider MR, Wolf E, Somech R, Klein C.(2021) Mammalian VPS45 orchestrates trafficking through the endosomal system. Blood. 2021 Apr 8;137(14):1932-1944

A. Ziv, L. Werner, L. Konnikova, A. Awad, T. Jeske, M. Hastreiter, V. Mitsialis, T. Stauber, S. Wall, D. Kotlarz, C. Klein, S. B. Snapper, Y. Tzfati, B. Weiss, R. Somech, and D. S. Shouval. (2020) An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency. J.Clin.Immunol. 40(7):1010-1019.

Yue Li, Christoph Klein, Daniel Kotlarz. (2020) Dysregulation of Cell Death in Human Chronic Inflammation. Cold Spring Harb Perspect Biol. 12(7):a037036.

Khoshnevisan R, Anderson M, Babcock S, Anderson S, Illig D, Marquardt B, Sherkat R, Schröder K, Moll F, Hollizeck S, Rohlfs M, Walz C, Adibi P, Rezaei A, Andalib A, Koletzko S, Muise AM, Snapper SB, Klein C, Thiagarajah JR, Kotlarz D. (2020) NOX1 Regulates Collective and Planktonic Cell Migration: Insights From Patients With Pediatric-Onset IBD and NOX1 Deficiency. Inflamm Bowel Dis. 26(8):1166-1176

Hager P, Mewes HW, Rohlfs M, Klein C, Jeske T. (2020) SmartPhase: Accurate and fast phasing of heterozygous variant pairs for genetic diagnosis of rare diseases. PloS Comput Biol. 7;16(2):e1007613.

Łyszkiewicz M, Ziętara N, Frey L, Pannicke U, Stern M, Liu Y, Fan Y, Puchałka J, Hollizeck S, Somekh I, Rohlfs M, Yilmaz T, Ünal E, Karakukcu M, Patiroğlu T, Kellerer C, Karasu E, Sykora KW, Lev A, Simon A, Somech R, Roesler J, Hoenig M, Keppler OT, Schwarz K, Klein C. (2020) Human FCHO1 deficiency reveals role for clathrin-mediated endocytosis in development and function of T cells. Nat.Commun.11(1):1031.

Somekh I, Thian M, Medgyesi D, Gülez N, Magg T, Gallón Duque A, Stauber T, Lev A, Genel F, Unal E, Simon AJ, Lee YN, Kalinichenko A, Dmytrus J, Kraakman MJ, Schiby G, Rohlfs M, Jacobson JM, Özer E, Akcal Ö, Conca R, Patiroglu T, Karakukcu M, Ozcan A, Shahin T, Appella E, Tatematsu M, Martinez-Jaramillo C, Chinn IK, Orange JS, Trujillo-Vargas CM, Franco JL, Hauck F, Somech R, Klein C, Boztug K. (2019) CD137 deficiency causes immune dysregulation with predisposition to lymphomagenesis. Blood. 134(18):1510-1516.

Jeske T, Huypens P, Stirm L, Höckele S, Wurmser CM, Böhm A, Weigert C, Staiger H, Klein C, Beckers J, Hastreiter M. (2019) DEUS: an R package for accurate small RNA profiling based on differential expression of unique sequences. Bioinformatics.35(22):4834-4836.

Li Y, Führer 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, Hönig M, Koletzko S, Muise AM, Snapper SB, Schwarz K, Klein C, Kotlarz D. (2019) Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases. Proc Natl Acad Sci U S A. 15;116(3):970-975.

Kotlarz, D, Marquardt B, Barøy T, Lee WS, Konnikova L, Hollizeck S, Magg T, Lehle AS, Walz C, Borggraefe I, Hauck F, Bufler P, Wall SM, Schumacher EM, Misceo D, Frengen E, Bentsen BS, Uhlig HH, Hopfner KP, Muise AM, Snapper SB, Strømme P, Klein C. (2018) Human Transforming Growth Factor Beta-1 Deficiency. Nat Genet. 50(3):344-348.

Witzel M, Petersheim D, Fan Y, Bahrami E, Racek T, Rohlfs M, Puchałka J, Mertes C, Gagneur J, Ziegenhain C, Enard W, Stray-Pedersen A, Arkwright PD, Abboud MR, Pazhakh V, Lieschke GJ, Krawitz PM, Dahlhoff M, Schneider MR, Wolf E, Horny HP, Schmidt H, Schäffer AA, Klein C. (2017) Chromatin remodelling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes. Nat Genet. 49(5):742-7525.

Boztug K, Järvinen PM, Salzer E, Racek T, Mönch S, Garncarz W, Gertz EM, Schäffer AA, Antonopoulos A, Haslam S, Ziesenitz L, Puchałka J, Diestelhorst J, Appaswamy G, Lescoeur B, Giambruno R, Bigenzahn JW, Elling U, Pfeifer D, Welte K, Brandes G, Sherkat R, van der Werff ten Bosch J, Rezaei N, Etzioni A, Bellanné-Chantelot C, Superti-Furga G, Penninger JM, Bennett KL, von Blume J, Dell A, Donadieu J, Klein C. (2014) JAGN1 deficiency causes aberrant myeloid cell homeostasis and congenital neutropenia. Nat Genet. 46(9):1021-7.

Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M, Modlich U, Beier R, Gohring G, Steinemann D, Fronza R, Ball CR, Haemmerle R, Naundorf S, Kuhlcke K, Rose M, Fraser C, Mathias L, Ferrari R, Abboud MR, Al-Herz W, Kondratenko I, Marodi L, Glimm H, Schlegelberger B, Schambach A, Albert MH, Schmidt M, von Kalle C, Klein C. (2014) Gene therapy for Wiskott-Aldrich syndrome–long-term efficacy and genotoxicity. Sci Transl Med. 6(227):227ra33

Vilboux T, Lev A, Malicdan MC, Simon AJ, Jarvinen P, Racek T, Puchalka J, Sood R, Carrington B, Bishop K, Mullikin J, Huizing M, Garty BZ, Eyal E, Wolach B, Gavrieli R, Toren A, Soudack M, Atawneh OM, Babushkin T, Schiby G, Cullinane A, Avivi C, Polak-Charcon S, Barshack I, Amariglio N, Rechavi G, van der Werff ten Bosch J, Anikster Y, Klein C, Gahl WA, Somech R. (2013) A congenital neutrophil defect syndrome associated with mutations in VPS45. N Engl J Med. 369(1):54-65.

Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Diez IA, Dewey RA, Bohm M, Nowrouzi A, Ball CR, Glimm H, Naundorf S, Kuhlcke K, Blasczyk R, Kondratenko I, Marodi L, Orange JS, von Kalle C, Klein C. (2010) Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med. 363(20):1918-27.

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, Klein C. (2009) Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. N Engl J Med. 361(21):2033-45.

Boztug K, Appaswamy G, Ashikov A, Schaffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F, Gatzke AK, Minkov M, Greil J, Kratz C, Petropoulou T, Pellier I, Bellanne-Chantelot C, Rezaei N, Monkemoller K, Irani-Hakimeh N, Bakker H, Gerardy-Schahn R, Zeidler C, Grimbacher B, Welte K, Klein C. (2009) A syndrome with congenital neutropenia and mutations in G6PC3. N Engl J Med. 360(1):32-43.

Bohn G, Allroth A, Brandes G, Thiel J, Glocker E, Schaffer AA, Rathinam C, Taub N, Teis D, Zeidler C, Dewey RA, Geffers R, Buer J, Huber LA, Welte K, Grimbacher B, Klein C. (2007) A novel human primary immunodeficiency syndrome caused by deficiency of the endosomal adaptor protein p14. Nat Med. 13(1):38-45

Klein C, Grudzien M, Appaswamy G, Germeshausen M, Sandrock I, Schäffer AA, Rathinam C, Boztug K, Schwinzer B, Rezaei N, Bohn G, Melin M, Carlsson G, Faeel B, Dahl N, Palmblad J, Henter JI, Zeidler C, Grimbacher B, Welte K. (2007) HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease). Nat Genet. 39(1):86-92.

Complete list of published work

Lear more about this strategic alliance supported by a pan-European EUREKA grant

Bone marrow organoids for deciphering inherited genetic defects

Dr. Stephanie Frenz-Wießner, Faculty of Medicine, has been awarded a doctoral prize from the Munich University Association for her dissertation, Stem cell-derived bone marrow organoids to model pediatric bone marrow failure syndromes.

Which genes and signaling pathways control the differentiation and functioning of the human blood and immune system? To further decipher these questions, Stephanie Frenz-Wießner researched a newly identified genetic defect associated with inherited bone marrow failure in her doctoral thesis. To investigate the cellular mechanisms within a model of the bone marrow niche, she created an innovative protocol for the generation of human stem cell-derived bone marrow organoids. The novel technology has been patented and provides a transformative platform for studying the basic biology of hematopoiesis and a broad spectrum of congenital and acquired diseases such as congenital bone marrow failure and childhood leukemias.

Dr. Frenz-Wießner currently works as a postdoc in the Broad Stem Cell Research Center at UCLA in Los Angeles.

Stephanie Frenz-Wiessner has successfully defended her PhD and has been awarded a Walter-Benjamin fellowship by the German Research Foundation (DFG) for her postdoctoral research in the lab of Hanna Mikkola at the Broad Stem Cell Research Center, UCLA, Los Angeles.

Organoids - three-dimensional miniature models of organs - are less than a millimetre in size. Ideally, they should be able to replicate the functions of their larger counterparts. An interdisciplinary team of scientists at the Dr. von Haunerschen Children's Hospital of the LMU has now succeeded in constructing human bone marrow organoids. "We believe that this technology could prove useful in many ways - from modelling congenital and acquired bone marrow diseases to the biotechnological production of blood cells," says Professor Christoph Klein, Director of the LMU Children's Hospital and Children's Polyclinic. In the journal Nature Methods, the team has described in detail their innovative method for generating these complex human bone marrow organoids from induced pluripotent stem cells.

More information:

https://www.lmu-klinikum.de/aktuelles/pressemitteilungen/ein-knochenmark-im-miniaturformat/b2654d9d92860337

Publication

Frenz-Wiessner et al., Generation of complex bone marrow organoids from human induced pluripotent stem cells, 2024, Nature Methods.

https://www.nature.com/articles/s41592-024-02172-2

Congratulation to all PhDs in medical research

On May, 12th 2022 we celebrated David Illig and other PhD graduates of the PhD program "Medical Research" in the Walter-Straub lecture hall.

Congratulations to all graduates!

Christoph Klein among the most influencial researchers 2021

In the Immunology field, Professor Christoph Klein (Director of Pediatric Clinic and Polyclinic, Dr. von Hauner Children’s Hospital and Gene Center at LMU) is ranked among the most highly cited researchers 2021. In total 15 researchers from LMU are among the most influencial authors in the ranking by the American Company Clarivate Analytics.

Gabriella Leung awarded a Humboldt Research Fellowship for Postdoctoral Researchers

Nach ihrem Ph.D. an der University of Calgary arbeitete Gabriella zuletzt als Post-Doc im Labor von Aleixo Muise am renommierten Hospital for Sick Children (SickKids) in Toronto, wo sie sich insbesondere der Erforschung der pathophysiologischen Mechanismen früh-manifester Formen chronisch-entzündlicher Darmerkrankungen widmete.

Ausgezeichnet mit einem prestigeträchtigen Humboldt Research Fellowship arbeitet Gabriella nun am Dr. von Haunerschen Kinderspital unter der Supervision von Prof. Dr. med. Dr. sci. nat. Christoph Klein an von induzierten pluripotenten Stammzellen abgeleiteten Makrophagenkulturen. Hiervon versprechen sich die Forscher ein besseres Verständnis der häufig sehr schwer und therapieresistent verlaufenden genetischen Formen chronisch-entzündlicher Darmerkrankungen.

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Daniel Petersheim wird bei seinem Phd durch die Hector Fellow Academy unterstützt.

Daniel Petersheim is awarded a Hector Fellow

Nach Abschluss seines Medizinstudiums an der Ludwig-Maximilians-Universität München mit Aufenthalten in Boston, New York und Zürich widmet sich Daniel nun einer wissenschaftlichen Arbeit im Rahmen des Ph.D. Programms „Genomic and Molecular Medicine – Personalized Approaches to Childhood Health“ am Dr. von Haunerschen Kinderspital unter der Supervision von Prof. Dr. med. Dr. sci. nat. Christoph Klein.

Unterstützt wird er hierbei durch ein Stipendium der Hector Fellow Academy. Die junge Wissenschaftsakademie, bestehend aus Professoren der MINT-Fächer, der Medizin sowie der Psychologie vernetzt Forscher über Fächergrenzen hinweg, bietet eine Plattform zum interdisziplinären Austausch und zur gegenseitigen Inspiration und fördert aussichtsreiche Nachwuchswissenschaftler auf vielfältige Weise.

Im Rahmen dieser Forschungsarbeit sollen mit Hilfe moderner Screening-Verfahren genetische Wechselwirkungen identifiziert werden, die den Effekten krankheitsauslösender Mutationen entgegenwirken. Dadurch soll der Weg hin zur Entwicklung zielgerichteter Therapien im Kontext seltener Erkrankungen geebnet werden. Hierzu kommen sowohl konventionelle Zelllinien als auch von Patienten gewonnene induzierte pluripotente Stammzellen zum Einsatz.