Margot Thome-Miazza - Sonderforschungsbereiches 854

Personal data
Curriculum Vitae: Margot Thome-Miazza
Name: THOME-MIAZZA, Margot
Date of birth: October 9 th , 1965
Place of birth: Stuttgart, Germany
Citizenship: German
Marital status: Married, two children
Work address: University of Lausanne
Department of Biochemistry
Chemin des Boveresses 155
CH-1066 Epalinges
Phone: ++ 41-21-692.57.37
Email: margot.thomemiazza@unil.ch
Website: http://www.unil.ch/ib/page9498.html
Education and Research
1985 High School Diploma, Filderstadt, Germany
1986 – 1991 Undergraduate and graduate studies of Biochemistry
University of Tübingen, Germany, and University of Arizona, USA
1992 Diploma thesis: “Molecular cloning of porcine T-cell receptors”
Laboratory of Dr. E. Pfaff, Federal Research Center for Virus
Diseases of Animals, Tübingen, Germany
1993 – 1995 Doctoral thesis: “Identification of ligands of the tyrosine kinase p56 lck ”
Laboratory of Dr. O. Acuto, Department of Molecular Immunology,
Pasteur Institute, Paris, France
1996 – 1998 Postdoctoral fellow at the University of Lausanne, Switzerland
Research project: “Signaling mechanisms in apoptosis”
Laboratory of Prof. Dr. J. Tschopp, Institute of Biochemistry
1999 – 2004 Research assistant (Maître Assistant), University of Lausanne
Research interest: “Signaling mechanisms regulating NF-κB activation”
Laboratory of Prof. Dr. J. Tschopp, Institute of Biochemistry
2004 – 2009 Assistant professor and group leader, University of Lausanne,
Department of Biochemistry
2009 – Associate professor and group leader, University of Lausanne,
Department of Biochemistry
Research interest: “Molecular mechanisms of lymphocyte activation in
T cells and B-cell lymphomas”

Fellowships and grants
Margot Thome-Miazza, CV and publication list
1993 – 1995 Doctoral fellowship from Boehringer Ingelheim Fonds (Germany)
1996 – 1998 Postdoctoral fellowship from the European Molecular Biology
Organization (EMBO, Germany)
1999 – 2010 Four consecutive grants from the Swiss Cancer League
2004 – 2010 Swiss National Science Foundation Fellow Professorship grant
2006 – 2007 Research grant from the Novartis Foundation (Switzerland)
2007 – 2008 Research grant from the Vontobel Foundation (Switzerland)
2008 – 2010 Research grant from the Pierre Mercier Foundation (Switzerland)
2009 Research prize, Leenaards Foundation
2009 Research prize, Cloëtta Foundation
2010 – 2011 Research grant, Swiss Multiple Sclerosis Society
2010 – 2011 Research grant, Novartis Consumer Health Foundation
Scientific memberships
Member of the MHV evaluation group of the Swiss National Science Foundation
Member and Assessor of the Swiss Society of Biochemistry
Editorial Board Member of the European Journal of Immunology
Reviewer for international journals
Antiviral Therapy J. Biol. Chem.
BBA J. Immunol.
Blood Leukemia
Cancer Res. Mol. Cell. Biol.
Cell Mol. Immunol.
Curr. Immunol. Rev. Nature
EMBO J. Oncogene
EMBO Reports Proc. Natl. Acad. Sci. USA
Eur. J. Immunol. Science
Immunity Trends Immunol.
External expert of grant applications
Swiss Cancer League
Swiss National Science Foundation
Wellcome Trust UK
French Ministry of Research
DKFZ (MOST program)
Israel Science Foundation
2

Oral presentations at conferences
Margot Thome-Miazza, CV and publication list
07/2001 11 th International Congress of Immunology (Stockholm, Sweden)
01/2002 International meeting “Signal Transduction 2002” (Luxembourg)
03/2002 Annual meeting of the Swiss Society for Allergology and Immunology
(Lugano, Switzerland)
05/2002 International EMBO workshop on “Lymphocyte antigen receptor and coreceptor
signaling” (Siena, Italy)
08/2002 Swiss Apoptosis Meeting (Bern, Switzerland)
10/2002 International Juan March meeting on “The control of NF-κB signal
transduction” (Madrid, Spain)
07/2004 International Congress of Immunology (Montreal, Canada)
09/2004 International EMBO workshop on “Lymphocyte antigen receptor and coreceptor
signaling” (Siena, Italy)
06/2007 4th International workshop on “Leukocyte signal transduction” (Rhodes,
Greece)
02/2008 Speaker and chairman, Keystone meeting on “Lymphocyte activation”
(Snowbird, Utah, US)
10/2008 Juan March Workshop: “Initiation of Antigen Receptor Signalling” (Madrid,
Spain)
04/2009 Invited speaker. ENII conference: “Tackling and Imaging the Complexity of
the Immune System” (Capo Caccia, Sardinia, Italy)
06/2009 Invited speaker. Aegean conference: “5 th Leukocyte Signal Transduction
Workshop” (Heraklion, Crete, Greece)
01/2010 Invited speaker. Keystone conference: “NF-kappaB in Inflammation and
Disease” (Santa Fe, New Mexico, US)
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Invited seminar speaker
Margot Thome-Miazza, CV and publication list
10/2002 University Complutense (Madrid, Spain). Host: Dr. Balbino Alarcon.
12/2002 Institut Pasteur (Paris, France). Hosts: Drs. Andres Alcover and Robert Weil.
01/2003 University Hospital Basel. Host: Dr. Ed Palmer.
01/2004 Institute for Research in Biomedicine, Bellinzona. Host: Dr. Marcus Thelen.
05/2004 Novartis Pharma AG, Department of Transplantation and Immunology
Research (Basel). Host: Dr. Jean-Pierre Evenou.
09/2004 Sonderforschungsbereich (SFB) seminar series of the Institute of Medical
Microbiology (University of Munich, Germany). Hosts: Dr. Jürgen Ruland /
Prof. Hermann Wagner.
01/2005 Institute of Pathology (University of Bern, Switzerland). Host: Dr. Thomi
Brunner.
04/2005 Institute for Medical Microbiology (University of Düsseldorf, Germany). Host:
Dr. Sandra Beer / Prof. Bernhard Holzmann.
03/2006 Institut Curie (Paris, France). Host: Dr. Claire Hivroz.
03/2006 Institut Cochin (Paris, France). Host: Drs. Alain Trautmann and Jérôme
Delon.
07/2006 Nikolaus-Fiebiger Centre (Erlangen, Germany). Hosts: Dirk Mielenz / Prof.
Hans-Martin Jäck.
10/2006 Sonderforschungsbereich (SFB) seminar series at the Medical University
Innsbruck (Austria). Host: Prof. Gottfried Baier.
03/2008 Novartis Pharma AG, Department of Transplantation and Immunology
Research (Basel). Host: Dr. Jean-Pierre Evenou.
09/2008 University of Freiburg (Breisgau, Germany). Hosts: Prof. Ralph Reski and
Prof. Michael Reth.
11/2008 University of Konstanz (Konstanz, Germany). Hosts: Prof. Marcus Groettrup
and Dr. Daniel Legler.
12/2008 University of Oxford (Oxford, Great Britain). Host: Dr. Oreste Acuto.
03/2009 Hôpital Henri Mondor (Paris, France). Host: Dr. Christiane Copie.
04/2009 University of Gent (Gent, Belgium). Host: Dr. Rudi Beyaert.
05/2010 NIH (Bethesda, MD, USA). Host: Dr. Pamela Schwartzberg.
11/2010 Hôpital Necker (Paris, France). Hosts: Drs. Gaël Ménasché et Sylvain Latour.
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Publications (# indicates the five best publications)
Margot Thome-Miazza, CV and publication list
Original publications
1. Thome, M., Saalmüller, A., and Pfaff, E. Molecular cloning of porcine T-cell
receptor� α,� β, �γ and� δ chains using PCR fragments of the constant regions. Eur.
J. Immunol. 23, 1005-1010 (1993).
2. Duplay, P., Thome, M., Hervé, F., and Acuto, O. p56 lck interacts via ist src
homology 2 domain with the ZAP-70 kinase. J. Exp. Med. 179, 1163-1170
(1994).
3. Thome, M., Duplay, P., Guttinger, M., and Acuto, O. Syk and ZAP-70 mediate
recruitment of p56 lck /CD4 to the activated T cell receptor/CD3/zeta complex. J.
Exp. Med. 181, 1997-2006 (1995).
4. Thome, M., Germain, V., DiSanto, J. P., and Acuto, O. The p56lck SH2
domain mediates recruitment of CD8/p56 lck to the activated T cell
receptor/CD3/zeta complex. Eur. J. Immunol. 26, 2093-2100 (1996).
5. Bodmer, J. L., Burns, K., Schneider, P., Hofmann, K., Steiner, V., Thome, M.,
Bornand, T., Hahne, M., Schroter, M., Becker, K., Wilson, A., French, L. E.,
Browning, J. L., MacDonald, H. R., and Tschopp, J. TRAMP, a novel
apoptosis-mediating receptor with sequence homology to tumor necrosis factor
receptor 1 and Fas(Apo-1/CD95). Immunity 6, 79-88 (1997).
#6. Thome, M., Schneider, P., Hofmann, K., Fickenscher, H., Meinl, E., Neipel, F.,
Mattmann, C., Burns, K., Bodmer, J. L., Schroter, M., Scaffidi, C., Krammer, P.
H., Peter, M. E., and Tschopp, J. Viral FLICE-inhibitory proteins (FLIPs)
prevent apoptosis induced by death receptors. Nature 386, 517-521 (1997).
#7. Irmler, M. 1 , Thome, M. 1 , Hahne, M., Schneider, P., Hofmann, K., Steiner, V.,
Bodmer, J. L., Schroter, M., Burns, K., Mattmann, C., Rimoldi, D., French, L. E.,
and Tschopp, J. Inhibition of death receptor signals by cellular FLIP. Nature
388, 190-195 (1997).
1 shared first authorship
8. Schneider, P., Bodmer, J. L., Thome, M., Hofmann, K., Holler, N., and
Tschopp, J. Characterization of two receptors for TRAIL. FEBS Letters 416,
329-334 (1997).
9. Schneider, P., Thome, M., Burns, K., Bodmer, J. L., Hofmann, K., Kataoka, T.,
Holler, N., and Tschopp, J. TRAIL receptors 1 (DR4) and 2 (DR5) signal
FADD-dependent apoptosis and activate NF-kappaB. Immunity 7, 831-836
(1997).
10. Kataoka, T., Schroter, M., Hahne, M., Schneider, P., Irmler, M., Thome, M.,
Froelich, C. J., and Tschopp, J. FLIP prevents apoptosis induced by death
receptors but not by perforin/granzyme B, chemotherapeutic drugs, and gamma
irradiation. J. Immunol. 161, 3936-3942 (1998).
11. Thome, M., Hofmann, K., Burns, K., Martinon, F., Bodmer, J. L., Mattmann, C.,
and Tschopp, J. Identification of CARDIAK, a RIP-like kinase that associates
with caspase-1. Curr. Biol. 8, 885-888 (1998).
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Margot Thome-Miazza, CV and publication list
12. Thome, M., Martinon, F., Hofmann, K., Rubio, V., Steiner, V., Schneider, P.,
Mattmann, C., and Tschopp, J. The equine herpesvirus-2 protein E10 but not
its cellular homologue activates NF-κB and c-Jun N-terminal kinase. J. Biol.
Chem., 274, 9962-9968 (1999).
13. Kataoka, T., Budd, R.C., Holler, N., Thome, M., Martinon, F., Irmler, M., Burns,
K., Hahne, M., Kennedy, N., Kovacsovics, M., and Tschopp, J. The caspase-8
inhibitor FLIP promotes activation of NF-κB and Erk signaling pathways. Curr.
Biol. 10, 640-648 (2000).
14. Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer,
J.-L., Schneider, P., Seed, B. and Tschopp, J. Fas triggers an alternative,
caspase-8–independent cell death pathway using the kinase RIP as effector
molecule. Nat. Immunol. 1, 489-495 (2000).
15. Thome, M. 1,2 , Gaide, O. 1 , Micheau, O., Martinon, F., Bonnet, D., Gonzalez, M.
and Tschopp, J. Equine herpesvirus protein E10 induces membrane
recruitment and phosphorylation of its cellular homologue, bcl-10. J. Cell Biol.
152, 1115-1122 (2001).
1 shared first authorship, 2 corresponding author
16. Siegmund, D., Mauri, D., Peters, N., Juo, P., Thome, M., Reichwein, M., Blenis,
J., Scheurich, P., Tschopp, J. and Wajant, H. FADD and Caspase-8 mediate
up-regulation of c-fos by FasL and TRAIL via a FLIP-regulated pathway. J.
Biol. Chem. 276, 32585-32590 (2001).
17. Gaide, O., Martinon, F., Micheau, O., Bonnet, D., Thome, M. 3 and Tschopp, J. 3
Carma1, a CARD-containing binding partner of Bcl10, induces Bcl10
phosphorylation and NF-κB activation. FEBS letters. 496, 121-127 (2001).
3 shared senior authorship
18. Aganna, E., Martinon, F., Hawkins, P.N., Ross, J.B., Swan, D.C., Booth, D.R.,
Lachmann, H.J., Gaudet, R., Woo, P., Feighery, C., Cotter, F.E., Thome, M.,
Hitman, G.A., Tschopp, J. and McDermott, M.F. Association of mutations in the
NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever,
cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum.
46, 2445-2452 (2002).
19. Micheau, O., Thome, M., Schneider, P., Holler, N., Tschopp, J., Nicholson, D.,
Briand, C. and Grutter, M.G. The long form of FLIP is an activator of Caspase-
8 at the Fas death-inducing signaling complex. J. Biol. Chem. 277, 45162-
45171 (2002).
20. Meylan, E., Martinon, F., Thome, M., Gschwendt, M. and Tschopp, J. RIP4
(DIK/PKK), a novel member of the RIP kinase family, activates NF-κB and is
processed during apoptosis. EMBO reports 3, 1201-1208 (2002).
#21. Gaide, O., Favier, B., Legler, D., Bonnet, D., Bron, C., Valitutti, S., Tschopp, J.
and Thome, M. Carma1 is a critical lipid raft-associated regulator of T-cell
receptor-induced NF-κB activation. Nat. Immunol. 3, 836-843 (2002).
22. Egawa, T., Albrecht, B., Favier, B., Sunshine, M.-J., Mirchandani, K., O’Brien,
W., Thome, M. and Littman, D.R. Requirement for CARMA1 in antigen
receptor-induced NF-κB activation and lymphocyte proliferation. Curr. Biol. 13,
1252-1258 (2003).
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Margot Thome-Miazza, CV and publication list
23. Teixeiro, M., Daniels, M.A., Hausmann, B., Schrum, A.G., Naeher, D.,
Luescher, I., Thome, M., Bragado, R. and Palmer, E. T Cell Division and
Death Are Segregated by Mutation of TCR Chain Constant Domains. Immunity
21, 515-526 (2004).
24. Thurau, M., Everett, H., Tapernoux, M., Tschopp, J. and Thome, M. The
TRAF3 binding site of human molluscipox virus FLIP molecule MC159 is critical
for its capacity to inhibit Fas-induced apoptosis. Cell Death Differ. 13, 1577-
1585 (2006).
25. Loeuillet, C., Martinon, F., Perez, C., Munoz, M., Thome, M. and Meylan, P.R.
Mycobacterium tuberculosis subverts innate immunity to evade specific
effectors. J. Immunol. 177, 6245-6255 (2006).
26. Rueda, D., Gaide, O., Ho, L., Lewkowicz, E., Niedergang, F., Hailfinger, S.,
Rebeaud, F., Guzzardi, M., Conne, B., Thelen, M., Delon, J., Ferch, U., Ruland,
J., Mak, T., Schwaller, J. and Thome, M. Bcl10 controls T-cell receptor- and
FcγR-induced actin polymerization. J. Immunol. 178, 4373–4384 (2007).
27. Misra, R.S., Russell, J.Q., Koenig, A., Hinshaw-Makepeace, J.A., Wen, R.,
Wang, D., Huo, H., Littman, D.R., Ferch, U., Ruland, J., Thome, M. and Budd,
R.C. Caspase-8 and c-FLIPL associate in lipid rafts with NF-κB adaptors
during T cell activation. J. Biol. Chem. 282,19365-19374 (2007).
28. Torgler, R., Bongfen, S.E., Romero, J.C., Tardivel, A., Thome, M. and
Corradin, G. Sporozoite-mediated hepatocyte wounding limits Plasmodium
parasite development via MyD88-mediated NF-κB activation and iNOS
expression. J. Immunol. 180, 3990-3999 (2008).
#29. Rebeaud, F., Hailfinger, S., Posevitz-Fejfar, A., Tapernoux, M., Moser, R.,
Rueda, D., Gaide, O., Guzzardi, M., Iancu, E.M., Rufer, N., Fasel, N. and
Thome, M. The proteolytic activity of MALT1 is key to T-cell activation. Nature
Immunol. 9, 272-281 (2008).
30. Thurau, M., Marquardt, G., Gonin-Laurent, N., Weinländer, K., Naschberger, E.,
Jochmann, R., Alkharsah, K.R., Schulz, T.F., Thome, M., Neipel, F., Stürzl, M.
The Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against
superoxide-induced cell death. J. Virol. 83, 598-611 (2009).
31. Brenner, D., Brechmann, M., Rohling, S., Tapernoux, M., Mock, T., Winter, D.
Lehmann, W.D., Kiefer, F., Thome, M., Krammer, P.H., and Arnold, R.
Phosphorylation of CARMA1 by HPK1 is critical for NF-κB activation in T cells.
Proc. Natl. Acad. Sci. USA 106, 14508-14513 (2009).
#32. Hailfinger, S., Lenz, G., Ngo, V., Posevitz-Fejfar, A., Rebeaud, F., Guzzardi, M.,
Murga penas, E., Dierlamm, J., Chan, W.C., Staudt, L.M. and Thome, M.
Essential role of MALT1 protease activity in activated B cell-like diffuse large Bcell
lymphoma. Proc. Natl. Acad. Sci. USA 106,19946-19951 (2009).
33. Schmid, D.A., Irving, M.B., Posevitz,V., Hebeisen, M., Posevitz-Fejfar, A.,
Sarria, J.C., Gomez-Eerland, R., Thome, M., Schumacher, T.N., Romero, P.,
Speiser, D.E., Zoete, V., Michielin, O., Rufer, N. Evidence for a TCR affinity
threshold delimiting maximal CD8 T cell function. J. Immunol. 184, 4936-4946
(2010).
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Margot Thome-Miazza, CV and publication list
Reviews
1. Thome, M., Hirt, W., Pfaff, E., Reddehase, M. J., and Saalmüller, A. Porcine Tcell
receptors: molecular and biochemical characterization. Vet. Immunol.
Immunopathol. 43, 13-16 (1994).
2. Thome, M. and Acuto, O. Molecular mechanism of T-cell activation: role of
protein tyrosine kinases in antigen receptor-mediated signal transduction. Res.
Immunol. 146, 291-307 (1995).
3. Meinl, E., Fickenscher, H., Thome, M., Tschopp, J., and Fleckenstein, B. Antiapoptotic
strategies of lymphotropic viruses. Immunol. Today 19, 474-9
(1998).
4. Tschopp, J., Irmler, M. and Thome, M. Inhibition of fas death signals by FLIPs.
Curr. Opin. Immunol. 10, 552-558 (1998).
5. Tschopp, J., Thome, M., Hofmann, K., and Meinl, E. The fight of viruses
against apoptosis. Curr. Opin. Gen. & Dev. 8, 82-87 (1998).
6. Thome, M. and Tschopp, J. Regulation of lymphocyte proliferation and death
by FLIP. Nat. Rev. Immunol. 1, 50-58 (2001).
7. Thome, M. and Tschopp, J. Bcl10. Curr. Biol. 12, R45 (2002).
8. Thome, M. Regulation of actin assembly in the immunological synapse: a
critical role for PKCθ. Dev. Cell 4, 3-5 (2003).
9. Thome, M. and Tschopp, J. TCR-induced NF-κB activation: a crucial role for
Carma1, Bcl10 and MALT1. Trends Immunol. 24, 419-424 (2003).
10. Thome, M. Carma1, Bcl10 and Malt1 in lymphocyte development and
activation. Nature Rev. Immunol. 4, 348-359 (2004).
11. Rueda, D. and Thome, M. Molecule page: Carma1. AfCS Nature Molecule
Pages. DOI:10.1038/mp.a003863.01 (2005).
12. Rueda, D. and Thome, M. Phosphorylation of Carma1: the link(er) to NF-κB
activation. Immunity 23, 551-553 (2005).
13. Rebeaud, F., Hailfinger, S. and Thome, M. Dlgh1 and Carma1 MAGUK
proteins contribute to signal specificity downstream of TCR activation. Trends
Immunol. 28, 196-200 (2007).
14. Thome, M. and Weil, R. Posttranslational modifications regulate distinct
functions of Carma1 and Bcl10. Trends Immunol. 28, 281-288 (2007).
15. Thome, M. Multifunctional roles for MALT1 in T-cell activation. Nature Rev.
Immunol. 9, 272-281 (2008).
16. Hailfinger, S., Rebeaud, F. and Thome, M. Adaptor and enzymatic functions of
proteases in T cell activation. Immunol. Rev. 232, 334-47 (2009).
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Margot Thome-Miazza, CV and publication list
17. Thome, M., Charton, J., Pelzer, C., and Hailfinger, S. Antigen receptor
signaling to NF-κB via CARMA1, BCL10 and MALT1. Cold Spring Harb
Perspect Biol. 2, a003004 (2010).
9