Experimental hematology Lab Prof. Dr. med. M.G. Manz

​Steffen Boettcher

Meeting the demands of mature blood cells under stress conditions

The hematopoietic system is characterized by its enormous proliferative capacities thereby ensuring maintenance of constant numbers of fully matured blood cells under steady-state conditions. For example, in humans approximately 10¹¹ – 10¹² blood cells are produced each day. However, under circumstances of hematopoietic challenges such as bleeding or infection the hematopoietic system is able to massively enhance its cellular throughput. Two prerequisites are crucial for a compensatory response to hematopoietic stress. First, disturbances of the hematopoietic equilibrium need to be rapidly sensed and second, these must be adequately translated into a cascade of events that lead to higher blood cell production and differentiation. We are trying to clarify regulatory mechanisms governing these functional properties. In particular, we are interested in how the highly functionally diverse bone marrow microenvironment is involved in these processes. Elucidation of these regulatory loops not only will help to gain better insight into the complex interplay between hematopoietic stem and progenitor cells and their supportive microenvironment but might eventually lead to identification of new avenues to more efficiently treat infections and/or blood diseases.

Understanding of hematopoietic stem cell dysfunction triggerd by chronic inflammation

Continuous blood cell formation is ensured by highly organized stepwise differentiation of lineage-committed progenitors that arise from self-renewing hematopoietic stem cells (HSCs). During chronic inflammation, e.g., infections, autoimmune diseases, replenishment of mature immune cells is in high demand at the site of reaction, which eventually induces HSC proliferation. Accumulation of divisional history in HSC results in functional impairment that would lead to elimination of dysfunctional clone in physiological conditions. However, given a certain condition that allows those clones to escape from normal regulatory control, it might increase rate of the genetic ablative events that leads to malignant transformation. Our aim is to characterize the molecular and epi-/genetic mechanisms which are responsible for HSC dysfunction during chronic inflammation, and further to study association of HSC cycling history with DNA mutational rate.

The bone marrow niche in health and disease

Self-renewing hematopoietic stem cells (HSC) capable of multilineage differentiation are the common ancestors of all types of blood cells. In order to exert their function, HSCs need to be tightly regulated by both intrinsic as well as extrinsic mechanisms. HSCs are located in the bone marrow in a microenvironment consisting of different types of supportive cells also called the HSC niche. The niche provides these extrinsic factors that are necessary for maintaining HSC functionality. Our goal is to identify those specific factors as well as to better characterize niche cells from which these signals originate. In addition, our work focusses on how the hematopoietic system changes as a consequence of naturally-occuring stress such as infection, bleeding and leukemic transformation and how the microenvironment is involved in the adaptation to this stress.

Larisa Kovtonyuk

Hematopoietic stem cell aging

Aging has an impact on function of all tissues and their respective stem cells, including the blood system. Hematopoiesis is an active ongoing process in which bone marrow (BM) resident hematopoietic stem cells (HSCs) continuously replenish all types of mature blood cells, most of them having a short life span. Aging has been shown to profoundly influence HSC function, as BM-homing ability, differentiation and self-renewal capacity. However, it remains unclear how HSC division and fate decision are changed during physiological aging and what determines HSC behaviour at a molecular level. We attempt to gain insight into intrinsic and extrinsic regulatory mechanisms of HSC aging, and search for understanding general rules that govern the aging processes.

Rouven Müller

Hematologic stem cell expansion in health and disease

Hematopoiesis is hierarchically organised and represents one of the best characterized adult stem cell systems. On top of the hierarchy, hematopoietic stem cells (HSCs) show the distinct features of long-term self-renewal and differentiation into the lineages of the hematopoietic system. While still little is known about the mechanisms that confer self-renewal and expansion of hematopoietic stem cells, hematopoietic stem cell transplantation has been performed since decades whereby a limited number of hematopoietic stem cells is capable in rescuing a patient whose bone marrow has been ablated by chemo- and/or radiotherapy.
As impressive the physiologic capacity of hematopoietic stem cells to expand on demand is, as feared are the devastating consequences of an aberrant regulation of self-renewal and expansion of their malignant counterparts leading to leukemia or myeloproliferative neoplasms (MPN).
In these clonal diseases, the existence of a minor fraction of the neoplastic cells termed leukemia initiating cells or leukemia stem cells has been proposed to propagate disease, being less susceptible to chemotherapy due to escape mechanisms and therefore leading to relapse after chemotherapy.
Within this project we are planning to characterize hematologic stem cell expansion in the mouse model, naturally occurring during embryofetal development and after birth as well as artificially induced by irradiation or chemotherapy. Knowledge gained here should help to decipher mechanisms responsible for human hematologic expansion.
In terms of malignant hematologic expansion leading to leukemia and myeloproliferative neoplasms we are planning to separate fractions of disease initiating cells in acute leukemias and myeloproliferative neoplasms in order to exactly define the disease initiating cells and to characterize their distinctive biological properties that could be selectively targeted in the future.

Anahita Rafiei

Establishment of human neoplasia in mice

We recently developed next-generation humanized mice that express multiple human cytokines. Upon demonstration that these mice are more suitable for the development and function of healthy human hematopoiesis, we now are testing the potential of these models to sustain primary human myeloid cell malignancies as e.g. myeoproliferative diseases, chronic myeloid leukemia, and Langerhans cell histiocytosis. Improved modelling will allow both, research on the underlying pathophysiology of such neoplastic diseases and preclinical predictive evaluation of new therapies.

Chakradhar Yakkala

Regulation of dendritic cell homeostasis

Dendritic cells (DC) are the antigen presenting cells that act as pedagogues for the generation of an immune response, which are short lived and need to be continuously replenished by the upstream hematopoietic stem and progenitor cells. FMS like tyrosine kinase 3 (Flt3) is a class III membrane bound tyrosine kinase receptor that has been shown to instruct the differentiation of upstream hematopoietic progenitors towards DC lineage, and is expressed on early hematopoietic progenitors, DC precursors and DCs. However, the regeneration kinetics of DC lineage by respective DC progenitors in the context of Flt3 signalling in steady state and under inflammatory conditions remains to be determined. We try to address this by generating and evaluating genetically engineered in vivo models.

2016

Das R, Strowig T, Verma R, Koduru S, Hafemann A, Hopf S, Kocoglu MH, Borsotti C, Zhang L, Branagan A, Eynon E, Manz MG, Flavell RA, Dhodapkar MV.
Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice.
Nat Med. 2016 Oct 10. (E pub ahead of print)
Pubmed   

Fridle C, Medinger M, Wilk MC, Seipel K, Passweg J, Manz MG, Pabst T.
Cladribine, cytarabine and idarubicin (CLA-Ida) salvage chemotherapy in relapsed acute myeloid leukemia (AML). 
Leuk Lymphoma. 2016 Oct 13:1-8
Pubmed

Ellegast JM, Rauch PJ, Kovtonyuk LV, Müller R, Wagner U, Saito Y, Wildner-Verhey van Wijk N, Fritz C, Rafiei A, Lysenko V, Dudkiewicz E, Theocharides AP, Soldini D, Goede JS, Flavell RA, Manz MG.
INV(16) and NPM1mut AML engraft human cytokine knock-in mice.
Blood. 2016 Aug 31. (E pub ahead of print)
Pubmed 

Rauch PJ, Ellegast JM, Widmer CC, Fritsch K, Goede JS, Valk PJ, Löwenberg B, Takizawa H, Manz MG.
MPL expression on AML blasts predicts peripheral blood neutropenia and thrombocytopenia.
Blood. 2016 Aug 29. ( E pub ahead of print)
Pubmed 

Saito Y, Ellegast JM, Rafiei A, Song Y, Kull D, Heikenwalder M, Rongvaux A, Halene S, Flavell RA, Manz MG.
Peripheral blood CD34+ cells efficiently engraft human cytokine knock-in mice.
Blood. 2016 Aug 19. (E pub ahead of print)
Pubmed

Luis TC, Tremblay CS, Manz MG, North TE, King KY, Challen G.
Inflammatory signals in HSPC development and homeostasis: Too much of a good thing?
Exp Hematol. 2016 Jul 15. (E pub ahead of print)
Pubmed

Versluis J, In't Hout FE, Devillier R, van Putten WL, Manz MG, Vekemans MC, Legdeur MC, Passweg JR, Maertens J, Kuball J, Biemond BJ, Valk PJ, van der Reijden BA, Meloni G, Schouten HC, Vellenga E, Pabst T, Willemze R, Löwenberg B, Ossenkoppele G, Baron F, Huls G, Cornelissen JJ.
Comparative value of post-remission treatment in cytogenetically normal AML subclassified by NPM1 and FLT3-ITD allelic ratio.
Leukemia. 2016 Jul 15. (E pub ahead of print)
Pubmed

Gerber B, Albeiro L, Rochat S, Stenner F, Manz MG, Buser A, Schanz U, Stussi G.
Safety and efficacy of cryopreserved autologous platelet concentrates in HLA-alloimmunized patients with hematologic malignancies.
Transfusion. 2016 Jun 24. (E pub ahead of print)
Pubmed

Kovtonyuk LV, Manz MG, Takizawa H.
Enhanced thrombopoietin but not G-CSF receptor stimulation induces self-renewing hematopoietic stem cell divisions in vivo.
Blood. 2016 May 4. (Epub ahead of print)
Pubmed

Saito Y, Ellegast J, Manz MG.
Generation of Humanized Mice for Analysis of Human Dendritic Cells.
Methods Mol Biol. 2016; 1423: 309-20.
Pubmed

Pietras EM, Mirantes-Barbeito C, Fong S, Loeffler D, Kovtonyuk LV, Zhang S, Lakshminarashimhan R, Chin CP, Techner JM, Will B, Nerlov C, Steidl U, Manz MG, Schroeder T, Passegué E.
Chronic interleukin-1 exposure drives haematopoietic stem cells towards precocious myeloid differentiation at the expense of self-renewal.
Nat Cell Biol. 2016 Apr 25. (Epub ahead of print)
Pubmed

Theocharides AP, Lundberg P, Lakkaraju AK, Lysenko V, Myburgh R, Aguzzi A, Skoda RC, Manz MG.
Homozygous Calreticulin mutations in patients with myelofibrosis lead to acquired myeloperoxidase deficiency.
Blood. 2016 Mar 24. (Epub ahead of print)
Pubmed

Theocharides AP, Rongvaux A, Fritsch K, Flavell RA, Manz MG.
Humanized hemato-lymphoid system mice.
Haematologica. 2016 Jan; 101 (1):5-19.
Pubmed

Boettcher S, Manz MG.
Sensing and translation of pathogen signals into demand-adapted myelopoiesis.
Curr Opin Hematol. 2016 Jan;23(1):5-10.
Pubmed

2015

Gemuenden C, Benz R, Senn O, Goede JS, Manz MG, Gerber B.
Efficacy of Azacitidine in De Novo and Relapsed Acute Myeloid Leukemia: A Retrospective Comparative Study.
Clin Lymphoma Myeloma Leuk. 2015 Dec;15(12):811-5. Epub 2015 Sep 25.
Pubmed

Ziegler P, Boettcher S, Takizawa H, Manz MG, Brümmendorf TH.
LPS-stimulated human bone marrow stroma cells support myeloid cell development and progenitor cell maintenance.
Ann Hematol. 2015 Nov 11. (Epub ahead of print)
Pubmed

Mehra T, Seifert B, Bravo-Reiter S, Wanner G, Dutkowski P, Holubec T, Moos RM, Volbracht J, Manz MG, Spahn DR.
Implementation of a patient blood managment monitoring and feedback program significantly reduces transfusions and costs.
Transfusion. 2015 Aug 11; (Epub ahead of print).
Pubmed

Mager LF, Riether C, Schürch CM, Banz Y, Wasmer MH, Stuber R, Theocharides AP, Li X, Xia Y, Saito H, Nakae S, Baerlocher GM, Manz MG, McCoy KD, Macpherson AJ, Ochsenbein AF, Beutler B, Krebs P.
IL-33 sginaling contributes to the pathogenesis of myeloproliferative neoplasms
J Clin Invest. 205 Jul 1;125(7):2579.91. Epub 2015 May 26.
Pubmed

Myburgh R, Ivic S, Pepper MS, Gers-Huber G, Li D, Audigé A, Rochat MA, Jaquet V, Regenass S, Manz MG, Salmon P, Krause KH, Speck RF.
Lentivector Knockdown of CCR5 in Hematopoietic Stem and Progenitor Cells Confers Functional and Persistent HIV-1 Resistance in Humanized Mice.
J Virol. 2015 Jul;89(13):6761-72. Epub 2015 Apr 22.
Pubmed

Berres ML, Kim KP, Peters T, Price J, Takizawa H, Salmon H, Idoyaga J, Ruzo A, Lupo PJ, Hicks MJ, Shih A, Simko SJ, Abhayankar H, Chakraborty R, Leboeuf M, Beltrao M, Lira SA, Heym KM, Clausen BE, Bigley V, Collin M, Manz MG, McClain K, Merad M, Allen CE.
BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups.
J Exp Med. 2015 Feb 9;212(2):281. Epub 2015 Feb 2.
Pubmed

2014

Boettcher S, Gerosa R, Radpour R, Bauer J, Ampenberger F, Heikenwälder M, Kopf M, Manz MG.
Endothelial cells translate pathogen signals into G-CSF-driven emergency granulopoiesis.
Blood. 2014; Aug 28;124(09):1393-9. Epub Jul 2014 Jul 2.
Pubmed

Sendoel A, Maida S, Zheng X, Teo Y, Stergiou L, Rossi CA, Subasic D, Pinto SM, Kinchen JM, Shi M, Boettcher S, Meyer JN, Manz MG, Bano D, Hengartner MO.
DEPDC1/LET-99 participates in an evolutionarily conserved pathway for anti-tubulin drug-induced apoptosis
Nat Cell Biol. 2014; Aug; 16(8):812-20. E pub 2014 Jul 27.
Pubmed

Sievert H, Pällmann N, Miller KK, Hermans-Borgmeyer I, Venz S, Sendoel A, Preukschas M, Schweizer M, Boettcher S, Janiesch PC, Streichert T, Walther R, Hengartner MO, Manz MG, Brümmendorf TH, Bokemeyer C, Braig M, Hauber J, Duncan KE, Balabanov S.
A novel mouse model for inhibition of DOHH-mediated hypusine modification reveals a crucial function in embryonic development, proliferation and oncogenic transformation.
Dis Model Mech. 2014 Aug 7;7(8):963-76.E pub 2014 May 15.
Pubmed

Gerber B, Köppel J, Paul M, Nguyen-Kim TD, Frauenfelder T, Nair G, Schanz U, Manz MG.
Efficacy of anti-fungal but not anti-bacterial prophylaxis in intensive primary AML therapy: a real-world, retrospective comparative single-centre study.
Swiss Med Wkly. 2014; Jul 31. (Epub ahead of print)
Pubmed

Bolisetty S, Boddupalli CS, Handschin S, Chaitanya K, Adamcik J, Saito Y, Manz MG, Mezzenga R.
Amyloid fibrils enhance transport of metal nanoparticles in living cells and induced cytotoxicity.
Biomacromolecules. 2014 Jul 14;15(7):2793-9. Epub 2014 Jun 30.
Pubmed

Rechsteiner M, Müller R, Reineke T, Goede J, Bohnert A, Zhong Q, Manz MG, Moch H, Wild PJ, Zimmermann DR, Tinguely M.
Modelling of a genetically diverse evolution of Systemic Mastocytosis with Chronic Myelomonocytic Leukemia (SM-CMML) by Next Generation Sequencing.
Exp Hematol Oncol. 2014; Jul 11; 3:18
Pubmed

Manz MG, Boettcher S.
Emergency granulopoiesis.
Nat Rev Immunol. 2014 May; 14 (5):302-14. E pub 2014 Apr 22.
Pubmed

Berres ML, Lim KP, Peters T, Price J, Takizawa H, Salmon H, Idoyaga J, Ruzo A, Lupo PJ, Hicks MJ, Shih A, Simko SJ, Abhyankar H, Chakraborty R, Leboeuf M, Heym KM, Bigley V, Collin M, Manz MG, McClain K, Merad M, Allen CE.
BRAF-V600E Expression in precursor versus differentiated dendritic cells defines clinically distinct LCH Risk-Groups.
J Exp Med. 2014 Mar 17. (Epub ahead of print)
Pubmed

Rongvaux A, Willinger T, Martinek J, Strowig T, Gearty SV, Teichmann LL, Saito Y, Marches F, Halene S, Palucka AK, Manz MG, Flavell Ra.
Development and function of human innate immune cells in a humanized mouse model.
Nat Biotechnol. 2014 Mar 16. (Epub ahead of print)
Pubmed

Strassberger V, Gutbrodt KL, Krall N, Roesli C, Takizawa H, Manz MG, Fugmann T, Neri D.
A comprehensive surface proteome analysis of myeloid leukemia cell lines for therapeutic antibody development.
J Proteomics, 2014 Jan.30; 138-151. (E pub ahead of print)
Pubmed

2013

Wueest S, Mueller R, Blüher M, Item F, Chin As, Wiedemann MS, Takizawa H, Kovtonyuk L, Chervonsky AV, Schoenle EJ, Manz MG, KonradD.
Fas (CD95) expression in myeloid cells promotes obesity-induced muscle insulin resistence.
EMBO Mol Med. 2013 Nov. 6. (Epub ahead of print)
Pubmed

Hauber I, Hofmann-Sieber H, Chemnitz J, Dubrau D, Chusainow J, Stucka R, Hartjen P, Schambach A, Ziegler P, Hackmann K, Schröck E, Schumacher U, Lindner C, Grundhoff A, Baum C, Manz MG, Buchholz F, Hauber J.
Highly Significant Antiviral Activity of HIV-1 LTR-Specific Tre-Recombinase in Humanized Mice.
PLoS Pathog. 2013 Sep; 9(9). Epub 2013 Sep 26.
Pubmed

Saito Y, Boddupalli CS, Borsotti C, Manz MG.
Dendritic cell homeostasis is maintained by nonhematopoietic and T-cell-produced Flt3-ligand in steady-state and during immune responses.
Eur J Immunol. 2013 Mar 21. (Epub ahead of print) PDF
Pubmed

Scotti C, Piccinini E, Takizawa H, Todorov A, Bourgine P, Papadimitropoulos A, Barbero A, Manz MG, Martin I.
Engineering of a functional bone organ through endochondral ossification.
Proc Natl Acad Sci USA. 2013 Feb 11. (Epub ahead of print)
Pubmed

Rongvaux A, Takizawa, Strowig T, Willinger T, Eynon EE, Flavell RA, Manz MG.
Human Hemato-Lymphoid System Mice: Current Use and Future Potential for Medicine.
Annu Rev. Immunol. 2013 Jan 16. (Epub ahead of print).
Pubmed

2012

Seleznik GM, Reding T, Romrig F, Saito Y, Mildner A, Segerer S, Sun LK, Regenass S, Lech M, Anders HJ, McHugh D, Kumagi T, Hiasa Y, Lackner C, Haybaeck J, Angst E, Perren A, Balmer ML, Slack E, Macpherson A, Manz MG, Weber A, Brownig JL, Arkan MC, Rülicke T, Aguzzi A, Prinz M, Graf R, Heikenwalder M.
Lymphotoxin B Receptor Signaling Promotes Development of Autoimmune Pancreatitis.
Gastroenterology. 2012 Nov; 143 (5): 1361-74. Epub 2012 Aug. 2.
Pubmed

Gerber B, Guggenberger R, Fasler D, Nair G, Manz MG, Stussi G, Schanz U.
Reversible skeletal disease and high fluoride serum levels in hematologic patients receiving voriconazole.
Blood. 2012 Sept 20; 120 (12):2390-4. Epub 2012 Aug 2.
Pubmed

Gerull S, Stern M, Ben Aissa A, Manz MG, Schanz U, Stussi G, Chalandon Y, Passweg J, Mohty B.
Allo-SCT for multiple myeloma in the era of novel agents: a retrospective study on behalf of Swiss Blood SCT.
Bone Marrow Transplant. 2012 Sep 3. (Epub ahead of print)
Pubmed

Takizawa H, Manz MG.
In vivo divisional tracking of hematopoietic stem cells.
Ann N Y Acad Sci. 2012 Aug; 1266: 40-6.
Pubmed

Wolf MJ, Hoos A, Bauer J, Boettcher S, Knust M, Weber A, Simonavicius N, Schneider C, Lang M, Stürzl M, Croner RS, Konrad A, Manz MG, Moch H, Aguzzi A, van Loo G, Pasparakis M, Prinz M, Borsig L, Heikenwalder M.
Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway.
Cancer Cell. 2012 Jul. 10; 22 (1): 91-105
Pubmed

Boettcher S, Ziegler P, Schmid MA, Takizawa H, van Rooijen N, Kopf M, Heikenwalder M, Manz MG.
Cutting Edge: LPS-Induced Emergency Myelopoiesis Depends on TLR4-Expressing Nonhematopoietic Cells.
J Immunol. 2012 Jun 15; 188 - (2): 5824-8. Epub 2012 May 14.
Pubmed

Takizawa H, Boettcher S, Manz MG.
Demand-adapted regulation of early hematopoiesis in infection and inflammation.
Blood. 2012 March 29; 119 (13): 2991-3002. Epub Jan 13. Review.
Pubmed

2011

Takizawa H, Schanz U, Manz MG.
Ex vivo expansion of hematopoietic stem cells: Mission accomplished?
Swiss Med Wkly. 2011 Dec 29; 141:0. (PubMed - in process)
Pubmed

Villaudy J, Wencker M, Gadot N, Gillet NA, Scoazec JY, Gazzolo L, Manz MG, Bangham CR, Dodon MD. HTLV-1 Propels Thymic Human T Cell Development in "Human Immune System" Rag2 gamma c Mice.
PLoS Pathog. 2011 Sep;7(9):e1002231. Epub 2011 Sep 1.
Pubmed

Schmid MA, Takizawa H, Baumjohann DR, Saito Y, Manz MG.
Bone marrow dendritic cell progenitors in mice sense pathogens via Toll-like receptors and subsequently migrate to inflamed lymph nodes.
Blood. 2011 Sep 9. (Epub ahead of print)
Pubmed

Rathinam C, Poueymirou WT, Rojas J, Murphy AJ, Valenzuela DM, Yancopoulos GD, Rongvaux A, Eynon EE, Manz MG, Flavell RA. Efficient differentiation and function of human macrophages in humanized CSF-1 mice.
Blood. 2011 Jul 25. (Epub ahead of print)
Pubmed

Strowig T, Rongvaux A, Rathinam C, Takizawa H, Borsotti C, Philbrick W, Eynon EE, Manz MG, Flavell RA. Transgenic expression of human signal regulatory protein alpha in Rag2-/-{gamma}c-/- mice improves engraftment of human hematopoietic cells in humanized mice.
Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13218-23. Epub 2011 Jul 25.
Pubmed

Takizawa H, Manz MG. Dynamic regulation of hematopoietic stem cell cycling. Cell Cycle. 2011 Jul 15;10(14):2246-7. Epub 2011 Jul 15.
Pubmed

Willinger T, Rongvaux A, Strowig T, Manz MG, Flavell RA. Improving human hemato-lymphoid-system mice by cytokine knock-in gene replacement.
Trends Immunol. 2011 Jul;32(7):321-7. Epub 2011 Jun 21.
Pubmed

Takizawa H, Regoes RR, Boddupalli CS, Bonhoeffer S, Manz MG. Dynamic variation in cycling of hematopoietic stem cells in steady state and inflammation.
J Exp Med. 2011;208:273-284
Pubmed

Rongvaux A, Willinger T, Takizawa H, Rathinam C, Auerbach W, Murphy AJ, Valenzuela DM, Yancopoulos GD, Eynon EE, Stevens S, Manz MG, Flavell RA. Human thrombopoietin knockin mice efficiently support human hematopoiesis in vivo.
Proc Natl Acad Sci U S A. 2011 Jan 24
Pubmed

Willinger T, Rongvaux A, Takizawa H, Yancopoulos GD, Valenzuela DM, Murphy AJ, Auerbach W, Eynon EE, Stevens S, Manz MG, Flavell RA. Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung. Proc Natl Acad Sci U S A. 2011 Jan 24.
Pubmed

2010

Song J, Willinger T, Rongvaux A, Eynon EE, Stevens S, Manz MG, Flavell RA, Galan JE. A mouse model for the human pathogen Salmonella typhi.
Cell Host Microbe 8, 369-376 (2010).
Pubmed

M. A. Schmid, D. Kingston, S. Boddupalli and M. G. Manz. Instructive cytokine signals in dendritic cell lineage commitment.
Immunol Rev 234, 32-44 (2010).
Pubmed

N. Onai, M. G. Manz and M. A. Schmid. Isolation of common dendritic cell progenitors (CDP) from mouse bone marrow.
Methods Mol Biol 595, 195-203 (2010).
Pubmed

B. Meek, S. Cloosen, C. Borsotti, C. H. Van Elssen, J. Vanderlocht, M. C. Schnijderberg, M. W. van der Poel, B. Leewis, R. Hesselink, M. G. Manz, Y. Katsura, H. Kawamoto, W. T. Germeraad and G. M. Bos. In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus.
Blood 115, 261-4 (2010).
Pubmed

F. Geissmann, M. G. Manz, S. Jung, M. H. Sieweke, M. Merad and K. Ley. Development of monocytes, macrophages, and dendritic cells.
Science327, 656-61 (2010).
Pubmed

2009

M. R. Neagu, P. Ziegler, T. Pertel, C. Strambio-De-Castillia, C. Grutter, G. Martinetti, L. Mazzucchelli, M. Grutter, M. G. Manz and J. Luban. Potent inhibition of HIV-1 by TRIM5-cyclophilin fusion proteins engineered from human components.
J Clin Invest 119, 3035-47 (2009).
Pubmed

M. Merad and M. G. Manz. Dendritic cell homeostasis.
Blood 113, 3418-27 (2009).
Pubmed

N. Martinez Soria, R. Tussiwand, P. Ziegler, M. G. Manz and O. Heidenreich. Transient depletion of RUNX1/RUNX1T1 by RNA interference delays tumour formation in vivo.
Leukemia 23, 188-90 (2009).
Pubmed

M. G. Manz and J. P. Di Santo. Renaissance for mouse models of human hematopoiesis and immunobiology.
Nat Immunol 10, 1039-42 (2009).
Pubmed

M. G. Manz. Flt3L, DCs, and NTregs: team contra GVHD?
Blood 113, 6267-8 (2009).
Pubmed

N. Legrand, A. Ploss, R. Balling, P. D. Becker, C. Borsotti, N. Brezillon, J. Debarry, Y. de Jong, H. Deng, J. P. Di Santo, S. Eisenbarth, E. Eynon, R. A. Flavell, C. A. Guzman, N. D. Huntington, D. Kremsdorf, M. P. Manns, M. G. Manz, J. J. Mention, M. Ott, C. Rathinam, C. M. Rice, A. Rongvaux, S. Stevens, H. Spits, H. Strick-Marchand, H. Takizawa, A. U. van Lent, C. Wang, K. Weijer, T. Willinger and P. Ziegler. Humanized mice for modeling human infectious disease: challenges, progress, and outlook.
Cell Host Microbe 6, 5-9 (2009).
Pubmed

D. Kingston, M. A. Schmid, N. Onai, A. Obata-Onai, D. Baumjohann and M. G. Manz. The concerted action of GM-CSF and Flt3-ligand on in vivo dendritic cell homeostasis.
Blood 114, 835-43 (2009).
Pubmed

2008

N. Onai and M. G. Manz. The STATs on dendritic cell development.
Immunity 28, 490-2 (2008).
Pubmed

M. Cocco, C. Bellan, R. Tussiwand, D. Corti, E. Traggiai, S. Lazzi, S. Mannucci, L. Bronz, N. Palummo, C. Ginanneschi, P. Tosi, A. Lanzavecchia, M. G. Manz and L. Leoncini. CD34+ cord blood cell-transplanted Rag2-/- gamma(c)-/- mice as a model for Epstein-Barr virus infection.
Am J Pathol 173, 1369-78 (2008).
Pubmed

S. Baenziger, P. Ziegler, L. Mazzucchelli, L. Bronz, R. F. Speck and M. G. Manz. Human T cell development and HIV infection in human hemato-lymphoid system mice.
Curr Top Microbiol Immunol 324, 125-31 (2008).
Pubmed

2007

H. Takizawa and M. G. Manz. Macrophage tolerance: CD47-SIRP-alpha-mediated signals matter.
Nat Immunol 8, 1287-9 (2007).
Pubmed

N. Onai, A. Obata-Onai, M. A. Schmid, T. Ohteki, D. Jarrossay and M. G. Manz. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow.
Nat Immunol 8, 1207-16 (2007).
Pubmed

N. Onai, A. Obata-Onai, M. A. Schmid and M. G. Manz. Flt3 in regulation of type I interferon-producing cell and dendritic cell development.
Ann N Y Acad Sci 1106, 253-61 (2007).
Pubmed

M. G. Manz. Human-hemato-lymphoid-system mice: opportunities and challenges.
Immunity 26, 537-41 (2007).
Pubmed

M. Gattorno, L. Chicha, A. Gregorio, F. Ferlito, F. Rossi, D. Jarrossay, A. Lanzavecchia, A. Martini and M. G. Manz. Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue. Rheumatology (Oxford) 46, 657-65 (2007).
Pubmed

2006

N. Onai, A. Obata-Onai, R. Tussiwand, A. Lanzavecchia and M. G. Manz. Activation of the Flt3 signal transduction cascade rescues and enhances type I interferon-producing and dendritic cell development.
J Exp Med 203, 227-38 (2006).
Pubmed

S. Baenziger, R. Tussiwand, E. Schlaepfer, L. Mazzucchelli, M. Heikenwalder, M. O. Kurrer, S. Behnke, J. Frey, A. Oxenius, H. Joller, A. Aguzzi, M. G. Manz and R. F. Speck. Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-gamma c-/- mice.
Proc Natl Acad Sci U S A 103, 15951-6 (2006).
Pubmed

2005

R. Tussiwand, N. Onai, L. Mazzucchelli and M. G. Manz. Inhibition of natural type I IFN-producing and dendritic cell development by a small molecule receptor tyrosine kinase inhibitor with Flt3 affinity.
J Immunol 175, 3674-80 (2005).
Pubmed

F. Macchiarini, M. G. Manz, A. K. Palucka and L. D. Shultz. Humanized mice: are we there yet?
J Exp Med 202, 1307-11 (2005).
Pubmed

H. Karsunky, M. Merad, I. Mende, M. G. Manz, E. G. Engleman and I. L. Weissman. Developmental origin of interferon-alpha-producing dendritic cells from hematopoietic precursors.
Exp Hematol 33, 173-81 (2005).
Pubmed

L. Chicha, R. Tussiwand, E. Traggiai, L. Mazzucchelli, L. Bronz, J. C. Piffaretti, A. Lanzavecchia and M. G. Manz. Human adaptive immune system Rag2-/-gamma(c)-/- mice.
Ann N Y Acad Sci 1044, 236-43 (2005).
Pubmed

2004

E. Traggiai, L. Chicha, L. Mazzucchelli, L. Bronz, J. C. Piffaretti, A. Lanzavecchia and M. G. Manz. Development of a human adaptive immune system in cord blood cell-transplanted mice.
Science 304, 104-7 (2004).
Pubmed

M. Merad, P. Hoffmann, E. Ranheim, S. Slaymaker, M. G. Manz, S. A. Lira, I. Charo, D. N. Cook, I. L. Weissman, S. Strober and E. G. Engleman. Depletion of host Langerhans cells before transplantation of donor alloreactive T cells prevents skin graft-versus-host disease.
Nat Med 10, 510-7 (2004).
Pubmed

C. H. Jamieson, L. E. Ailles, S. J. Dylla, M. Muijtjens, C. Jones, J. L. Zehnder, J. Gotlib, K. Li, M. G. Manz, A. Keating, C. L. Sawyers and I. L. Weissman. Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML.
N Engl J Med 351, 657-67 (2004).
Pubmed

L. Chicha, D. Jarrossay and M. G. Manz. Clonal type I interferon-producing and dendritic cell precursors are contained in both human lymphoid and myeloid progenitor populations.
J Exp Med 200, 1519-24 (2004).
Pubmed

W. Brugger, J. Hirsch, F. Grunebach, R. Repp, P. Brossart, W. Vogel, H. G. Kopp, M. G. Manz, M. Bitzer, G. Schlimok, M. Kaufmann, A. Ganser, K. Fehnle, M. Gramatzki and L. Kanz. Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: a prospective, multicenter phase II study.
Ann Oncol 15, 1691-8 (2004).
Pubmed

2003

M. Kondo, A. J. Wagers, M. G. Manz, S. S. Prohaska, D. C. Scherer, G. F. Beilhack, J. A. Shizuru and I. L. Weissman. Biology of hematopoietic stem cells and progenitors: implications for clinical application.
Annu Rev Immunol 21, 759-806 (2003).
Pubmed

H. Karsunky, M. Merad, A. Cozzio, I. L. Weissman and M. G. Manz. Flt3 ligand regulates dendritic cell development from Flt3+ lymphoid and myeloid-committed progenitors to Flt3+ dendritic cells in vivo.
J Exp Med 198, 305-13 (2003).
Pubmed

D. Chatterjea-Matthes, M. E. Garcia-Ojeda, S. Dejbakhsh-Jones, L. Jerabek, M. G. Manz, I. L. Weissman and S. Strober. Early defect prethymic in bone marrow T cell progenitors in athymic nu/nu mice.
J Immunol 171, 1207-15 (2003).
Pubmed

2002

M. Merad, M. G. Manz, H. Karsunky, A. Wagers, W. Peters, I. Charo, I. L. Weissman, J. G. Cyster and E. G. Engleman. Langerhans cells renew in the skin throughout life under steady-state conditions.
Nat Immunol 3, 1135-41 (2002).
Pubmed

M. G. Manz, T. Miyamoto, K. Akashi and I. L. Weissman. Prospective isolation of human clonogenic common myeloid progenitors.
Proc Natl Acad Sci U S A 99, 11872-7 (2002).
Pubmed

M. G. Manz, C. Berger, H. P. Horny, R. Beck, W. Brugger, R. Viebahn, L. Kanz and H. Knecht. Sustained remission of an extensive monoclonal, Epstein-Barr virus-associated diffuse large B cell lymphoma in a kidney-pancreas transplant recipient.
Transplantation 73, 995-7 (2002).
Pubmed

2001

M. G. Manz, D. Traver, T. Miyamoto, I. L. Weissman and K. Akashi. Dendritic cell potentials of early lymphoid and myeloid progenitors.
Blood 97, 3333-41 (2001).
Pubmed

M. G. Manz, D. Traver, K. Akashi, M. Merad, T. Miyamoto, E. G. Engleman and I. L. Weissman. Dendritic cell development from common myeloid progenitors. Ann N Y Acad Sci 938, 167-73; discussion 173-4 (2001).
Pubmed

M. Kondo, D. C. Scherer, A. G. King, M. G. Manz and I. L. Weissman. Lymphocyte development from hematopoietic stem cells.
Curr Opin Genet Dev 11, 520-6 (2001).
Pubmed

2000

Traver, D., Akahshi, K., Manz, M., et al. Development of CD8alpha-positive dendritic cells from a common myeloid progenitor.
Science 290, 2152-2154 (2000).
Pubmed

1998

M. G. Manz, A. Melms, N. Sommer and C. A. Muller. Myasthenia gravis and tumor necrosis factor beta polymorphisms: linkage disequilibrium but no association beyond HLA-B8.
J Neuroimmunol 90, 187-91 (1998).
Pubmed