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Doctorate in Aging Biology (Ph.D.), University Paris VII - Laboratory of Human
Immunopathology, INSERM U430, Paris, France
Myocardial fibrosis in experimental hypertension: role of hormonal and inflammatory factors
Post-Doctoral training at the Karolinska Institute, Stockholm, Sweden - 2 year grant from the
European Union’s "Training and Mobility for Researchers" program
Mechanism of autoimmunity in atherosclerosis
Assistant Professor at the Paris VI University - Research activity in the INSERM U430, of the
UMRS 681 and of the Tema 16 UMRS872 (CRC), Paris, France
Function and modulation of specific immunity in atherosclerosis
HDR : “Habilitation à Diriger des Recherches” - Paris VI University

I perform my teaching duties (>250 h/year) at the University Pierre et Marie Curie (Paris 6) in ‘Immunology’
(section CNU 65) for the undergraduate and post graduate students. The syllabus includes fol owing courses :
Immune tolerance workshop (principal coordinator Immunopathophysiology (principal coordinator) Advanced flow cytometry workshop (principal

In vivo and in vitro gene transfer by Adherent (vascular cel s) and non- flow cytometry; Cel proliferation; Cytokine production ; In vivo biophotonic imaging method for col agen by polarized light microscopy
• Since I joined the UMRS681, I lead the group working on the modulation of the immune response as a
therapeutic tool in vascular pathologies. This group is composed of a CR1 INSERM researcher, a ‘research engineer’ from the University of Paris 6, and an INSERM research technician. We are supervising 4 students (3 PhD and 1 master’s student). Since 1998, I have supervised 1 post-doc fel ow (B Poirier), 4 PhD students (E Tupin, O Thaunat, A Varthaman, E Groyer), and 3 master’s students (M Vandaele, E Laurat, A Gadzinski) • Since 2003, I have been a jury member for 15 PhD thesis defense • I am an elected member of the scientific council of the Centre de Recherche des Cordeliers and a member of the steering committee of the central animal facility and of the Internet and the Intranet facilities of the campus • I am an active member of the regional ethical committee for animal experimentation (CREEA Ile de France • Member of the organizing committee of the French Science Festival • Co-organizer of an international symposium entitled ‘Infl ammation, an unexpected guest in chronic diseases?’ (Centre de Recherche des Cordeliers, Sept 2006)
• Reviewer for Circulation, Atherosclerosis, Thrombosis and Vascular Biology, The Journal of Experimental
• Invited speaker at the symposium of the Journal of Internal Medicine (Stockholm, Octobre 2007). • I have obtained several research grants including the Claude Bernard foundation, ‘La Fondation de France’. I have been serving as a co-PI for research projects supported by public and private granting agencies such as Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, CSL-Behring, LFB, Bayer, Octapharma • Fluent in English and Italian • Expert in informatics and creator of the web site of the unit • Co-inventor of the patent “Atherosclerosis vaccine”. Hansson GK, Wutgge D, Stemme S, Nicoletti A. - Patent PCT/SE01/00570 - june 2000. This patent is based on the identification of the T cel epitopes of oxidized LDL and relies on the use of a vaccinal strategy to treat atherosclerosis

1. Thaunat O., Louedec L., Graff-Dubois S., Dai J., Groyer E., 8. Thaunat O., Louedec L., Dai J., Bellier F., Groyer E.,
Yacoub-Youssef H., Mandet C., Bruneval P., Kaveri S., Delignat S., Gaston A. T., Caligiuri G., Joly E., Caligiuri G., Germain S., Michel J. B., and Nicoletti A. In Plissonnier D., Michel J. B., and Nicoletti A. 2006. Direct press. Anti-angiogenic treatment prevents adventitial and Indirect Effects of Alloantibodies Link Neointimal and Transplantation.
Arterioscler Thromb Vasc Biol 26:2359-2365.
2. Thaunat O., Patey N., Michel J. B., and Nicoletti A. 2007. Is 9. Thaunat O., Kerjaschki D., and Nicoletti A. 2006. Is
lymphoid neogenesis a therapeutic target for chronic defective lymphatic drainage a trigger for lymphoid rejection? Am J Transplant 7:1312-1313.
neogenesis? Trends Immunol 27:441-445.
3. Monteiro M., Evaristo C., Legrand A., Nicoletti A., and 10.Thaunat O., Field A. C., Michel J. B., and Nicoletti A.
Rocha B. 2007. Cartography of gene expression in CD8 2006. [Implication of the lymphoid neogenesis process in single cells: novel CCR7- subsets suggest differentiation chronic rejection.]. Med Sci (Paris) 22:110-111.
independent of CD45RA expression. Blood 109:2863- 11.Khallou-Laschet J., Tupin E., Caligiuri G., Poirier B.,
Thieblemont N., Gaston A. T., Vandaele M., Bleton J., 4. Michel J. B., Thaunat O., Houard X., Meilhac O., Caligiuri
Tchapla A., Kaveri S. V., Rudling M., and Nicoletti A. G., and Nicoletti A. 2007. Topological determinants and consequences of adventitial responses to arterial wall apolipoprotein E knockout mice. Atherosclerosis
injury. Arterioscler Thromb Vasc Biol 27:1259-1268.
5. Groyer E., Nicoletti A., Ait-Oufella H., Khallou-Laschet J., 12.Khallou-Laschet J., Caligiuri G., Groyer E., Tupin E.,
Varthaman A., Gaston A. T., Thaunat O., Kaveri S. V., Gaston A. T., Poirier B., Kronenberg M., Cohen J. L., Blatny R., Stockinger H., Mallat Z., and Caligiuri G. 2007. Klatzmann D., Kaveri S. V., and Nicoletti A. 2006. The Atheroprotective effect of CD31 receptor globulin through proatherogenic role of T cells requires cell division and is enrichment of circulating regulatory T-cells. J Am Coll
dependent on the stage of the disease. Arterioscler
Cardiol 50:344-350.
Thromb Vasc Biol 26:353-358.
6. Caligiuri G., Khallou-Laschet J., Vandaele M., Gaston A. 13.Groyer E., Caligiuri G., Laschet-Khallou J., and Nicoletti
T., Delignat S., Mandet C., Kohler H. V., Kaveri S. V., and A. 2006. [Immunological aspects of atherosclerosis]. Presse Med 35:475-486.
immunization reduces atherosclerosis. J Am Coll Cardiol 14.Duong Van Huyen J. P., Delignat S., Bayry J.,
Kazatchkine M. D., Bruneval P., Nicoletti A., and Kaveri 7. Thaunat O., Patey N., Morelon E., Michel J. B., and
S. V. 2006. Interleukin-12 is associated with the in vivo Nicoletti A. 2006. Lymphoid neogenesis in chronic anti-tumor effect of mistletoe extracts in B16 mouse rejection: the murderer is in the house. Curr Opin
melanoma. Cancer Lett.
Immunol 18:576-579.
15.Demigne C., Bloch-Faure M., Picard N., Sabboh H.,
cells in the blood of atherosclerotic mice with plaque Besson C., Remesy C., Geoffroy V., Gaston A. T., Nicoletti thrombosis. Arterioscler Thromb Vasc Biol 25:1659-
A., Hagege A., Menard J., and Meneton P. 2006. Mice chronically fed a westernized experimental diet as a model 27.Tupin E., Nicoletti A., Elhage R., Rudling M., Ljunggren
of obesity, metabolic syndrome and osteoporosis. H. G., Hansson G. K., and Berne G. P. 2004. CD1d- European journal of nutrition 45:298-306.
dependent activation of NKT cells aggravates 16.Caligiuri G., Rossignol P., Julia P., Groyer E., Mouradian
atherosclerosis. J Exp Med 199:417-422.
D., Urbain D., Misra N., Ollivier V., Sapoval M., Boutouyrie 28.Tupin E., Poirier B., Bureau M. F., Khallou-Laschet J.,
P., Kaveri S. V., Nicoletti A., and Lafont A. 2006. Reduced Vranckx R., Caligiuri G., Gaston A. T., Duong Van immunoregulatory CD31+ T cells in patients with Huyen J. P., Scherman D., Bariety J., Michel J. B., and atherosclerotic abdominal aortic aneurysm. Arterioscler
Nicoletti A. 2003. Non-viral gene transfer of murine Thromb Vasc Biol 26:618-623.
spleen cells achieved by in vivo electroporation. Gene
17.Caligiuri G., Kaveri S. V., and Nicoletti A. 2006. IL-20 and
Ther 10:569-579.
atherosclerosis: another brick in the wall. Arterioscler 29.Nicoletti A., and Caligiuri G. 2003. Les lymphocytes et
Thromb Vasc Biol 26:1929-1930.
18.Bayary J., Dasgupta S., Misra N., Ephrem A., Duong Van
Huyen J. P., Delignat S., Hassan G., Caligiuri G., Nicoletti thérapeutiques. J. F. Toussaint, M. P. Jacob, L. Lagrost, A., Lacroix-Desmazes S., Kazatchkine M. D., and Kaveri S. and J. Chapman, eds. Masson, Paris. 112-146. 2006. Intravenous immunoglobulin in autoimmune 30.Kohler H., Bayry J., Nicoletti A., and Kaveri S. V. 2003.
disorders: An insight into the immunoregulatory Natural autoantibodies as tools to predict the outcome of mechanisms. Int Immunopharmacol 6:528-534.
immune response? Scand J Immunol 58:285-289.
19.Thaunat O., Field A. C., Dai J., Louedec L., Patey N., 31.Gervais M., Pons S., Nicoletti A., Cosson C., Giudicelli J.
Bloch M. F., Mandet C., Belair M. F., Bruneval P., Meilhac F., and Richer C. 2003. Fluvastatin prevents renal O., Bellon B., Joly E., Michel J. B., and Nicoletti A. 2005. dysfunction and vascular NO deficit in apolipoprotein E- Lymphoid neogenesis in chronic rejection: evidence for a deficient mice. Arterioscler Thromb Vasc Biol 23:183-
local humoral alloimmune response. Proc Natl Acad Sci U
S A 102:14723-14728.
32.Gaertner R., Lepailleur-Enouf D., Gonzalez W., Nicoletti
20.Thaunat O., Caligiuri G., Nicoletti A., and Michel J. B.
A., Mandet C., Philippe M., Mercadier J. J., and Michel J. 2005. Complexity of antigenic determinants and humoral B. 2003. Pulmonary endothelium as a site of synthesis responses in vascular injury. Cardiovasc Res 68:183-185.
and storage of interleukin-6 in experimental congestive 21.Persson L., Borén J., Nicoletti A., Hansson G. K., and
heart failure. Eur J Heart Fail 5:435-442.
Pekna M. 2005. Immunoglobulin treatment reduces 33.Caligiuri G., Stahl D., Kaveri S., Irinopoulous T., Savoie
atherosclerosis in apolipoprotein E–/– low-density F., Mandet C., Vandaele M., Kazatchkine M. D., Michel lipoprotein receptor–/– mice via the complement system. J. B., and Nicoletti A. 2003. Autoreactive antibody Clin Exp Immunol 142:441-445.
repertoire is perturbed in atherosclerotic patients. Lab
22.Misra N., Bayry J., Ephrem A., Dasgupta S., Delignat S.,
Invest 83:939-947.
Van Huyen J. P., Prost F., Lacroix-Desmazes S., Nicoletti 34.Caligiuri G., Rudling M., Ollivier V., Jacob M. P., Michel
A., Kazatchkine M. D., and Kaveri S. V. 2005. Intravenous J. B., Hansson G. K., and Nicoletti A. 2003. Interleukin- immunoglobulin in neurological disorders: a mechanistic 10 deficiency increases atherosclerosis, thrombosis, and perspective. J Neurol 252 Suppl 1:I1-6.
low-density lipoproteins in apolipoprotein E knockout 23.Misra N., Bayary J., Dasgupta S., Ephrem A., Huyen J. P.,
mice. Mol Med 9:10-17.
Delignat S., Hassan G., Caligiuri G., Nicoletti A., Lacroix- 35.Kuo C. C., Campbell L. A., Rosenfeld M. E., Caligiuri G.,
Desmazes S., Kazatchkine M. D., and Kaveri S. V. 2005. Rottenberg M., Wigzell H., Hansson G. K., and Nicoletti Intravenous immunoglobulin and dendritic cells. Clinical
A. 2002. Chlamydia pneumoniae infection and reviews in allergy & immunology 29:201-205.
24.Khallou-Laschet J., Caligiuri G., Tupin E., Gaston A. T.,
response. Circulation 105:34.
Poirier B., Groyer E., Urbain D., Maisnier-Patin S., Sarkar 36.Fournier N., Cogny A., Atger V., Pastier D.,
R., Kaveri S. V., Lacroix-Desmazes S., and Nicoletti A. Goudouneche D., Nicoletti A., Moatti N., Chambaz J., 2005. Role of the intrinsic coagulation pathway in Paul J. L., and Kalopissis A. D. 2002. Opposite effects of atherogenesis assessed in hemophilic apolipoprotein E plasma from human ApoA-II transgenic mice on knockout mice. Arterioscler Thromb Vasc Biol 25:e123-
cholesterol efflux from J774 macrophages and Fu5AH hepatoma cells. Arterioscler Thromb Vasc Biol
25.Caligiuri G., Kaveri S., and Nicoletti A. 2005. When
interleukin-18 conducts, the Preludio sounds the same no 37.Duong Van Huyen J. D., Bayry J., Delignat S., Gaston A.
matter who plays. Arterioscler Thromb Vasc Biol 25:655-
T., Michel O., Bruneval P., Kazatchkine M. D., Nicoletti A., and Kaveri S. 2002. Induction of apoptosis of 26.Caligiuri G., Groyer E., Khallou-Laschet J., Al Haj Zen A.,
endothelial cells by Viscum album: A role for anti-tumoral Sainz J., Urbain D., Gaston A. T., Lemitre M., Nicoletti A., properties of mistletoe lectins. Mol Med 8:600-606.
and Lafont A. 2005. Reduced immunoregulatory CD31+ T 38.Caligiuri G., Nicoletti A., Poirier B., and Hansson G. K.
2002. Protective immunity against atherosclerosis carried 52.Caligiuri G., Nicoletti A., Zhou X., Tornberg I., and
by B cells of hypercholesterolemic mice. J. Clin. Invest.
Hansson G. K. 1999. Effects of sex and age on atherosclerosis and autoimmunity in apoE- deficient 39.Bruneval P., Bariety J., Belair M. F., Mandet C., Heudes
mice. Atherosclerosis 145:301-308.
D., and Nicoletti A. 2002. Mesangial expansion associated 53.Nicoletti A., and Sassy-Prigent C. 1998. Alternative
with glomerular endothelial cell activation and macrophage
quantitative PCR method. In Gene cloning and analysis recruitment is developing in hyperlipidaemic apoE null by RT-PCR. P. B. Siebert, and J. W. Larrick, eds. Eaton mice. Nephrol Dial Transplant 17:2099-2107.
40.Laurat E., Poirier B., Tupin E., Caligiuri G., Hansson G. K., 54.Nicoletti A., Kaveri S., Caligiuri G., Bariety J., and
Bariety J., and Nicoletti A. 2001. In vivo downregulation of Hansson G. K. 1998. Immunoglobulin treatment reduces T helper cell 1 immune responses reduces atherogenesis atherosclerosis in apo E knockout mice. J Clin Invest
in apolipoprotein E-knockout mice. Circulation 104:197-
55.Nicoletti A., and Sassy-Prigent C. 1996. An alternative
41.Caligiuri G., Rottenberg M., Nicoletti A., Wigzell H., and
quantitative polymerase chain reaction method. Hansson G. K. 2001. Chlamydia pneumoniae infection Analytical biochemistry 236:229-241.
does not induce or modify atherosclerosis in mice. 56.Nicoletti A., Mandet C., Challah M., Bariety J., and
Circulation 103:2834-2838.
Michel J. B. 1996. Mediators of perivascular 42.Zhou X., Nicoletti A., Elhage R., and Hansson G. K. 2000.
inflammation in the left ventricle of renovascular Transfer of CD4(+) T cells aggravates atherosclerosis in hypertensive rats. Cardiovasc Res 31:585-595.
mice. 57.Nicoletti A., Heudes D., Mandet C., Hinglais N., Bariety
Circulation 102:2919-2922.
J., and Michel J. B. 1996. Inflammatory cells and 43.Pueyo M. E., Gonzalez W., Nicoletti A., Savoie F., Arnal J.
myocardial fibrosis: spatial and temporal distribution in F., and Michel J. B. 2000. Angiotensin II stimulates renovascular hypertensive rats. Cardiovasc Res
endothelial vascular cell adhesion molecule-1 via nuclear factor-kappaB activation induced by intracellular oxidative 58.Zhuang Y. F., Corone-Alden S., Duval A. M., Benvenuti
stress. Arterioscler Thromb Vasc Biol 20:645-651.
C., Albo C., Deleuze P., Loisance D., Benhayem N., 44.Nicoletti A., Paulsson G., Caligiuri G., and Hansson G. K.
Heudes D., Nicoletti A., and et al. 1995. Right ventricular 2000. Induction of neonatal tolerance to oxidized-LDL late filling termination time and its relation to interstitial reduces atherosclerosis susceptibility in apoE knockout collagen content in early transplanted heart: a color M- mice. Mol Med 6:283-290.
mode Doppler digital analysis. J Heart Lung Transplant
45.Nicoletti A., Caligiuri G., and Hansson G. K. 2000.
Immunomodulation of atherosclerosis: myth and reality. J 59.Nicoletti A., Heudes D., Hinglais N., Appay M. D.,
Intern Med 247:397-405.
Philippe M., Sassy-Prigent C., Bariety J., and Michel J. 46.Caligiuri G., Paulsson G., Nicoletti A., Maseri A., and
B. 1995. Left ventricular fibrosis in renovascular Hansson G. K. 2000. Evidence for antigen-driven T-cell hypertensive rats. Effect of losartan and spironolactone. response in unstable angina. Circulation 102:1114-1119.
Hypertension 26:101-111.
47.Caligiuri G., and Nicoletti A. 2000. Origines infectieuses de 60.Michel J. B., Nicoletti A., and Arnal J. F. 1995. Left
l'athérosclérose. Médecine et thérapeutiques 6:593-597.
myocardial infarction. Eur Heart J 16:49-57.
48.Nicoletti A., and Michel J. B. 1999. Cardiac fibrosis and
inflammation: interaction with hemodynamic and hormonal 61.Challah M., Nicoletti A., Arnal J. F., Philippe M.,
factors. Cardiovasc Res 41:532-543.
Laboulandine I., Allegrini J., Alhenc-Gelas F., Danilov S., and Michel J. B. 1995. Cardiac angiotensin converting 49.Nicoletti A., Caligiuri G., Tornberg I., Kodama T., Stemme
enzyme overproduction indicates interstitial activation in S., and Hansson G. K. 1999. The macrophage scavenger renovascular hypertension. Cardiovasc Res 30:231-
receptor type A directs modified proteins to antigen presentation. Eur J Immunol 29:512-521.
62.Michel J. B., Hinglais N., Nicoletti A., and Arnal J. F.
50.Nicoletti A., Caligiuri G., Paulsson G., and Hansson G. K.
1994. Remodelage ventriculaire et collagène cardiaque. 1999. Functionality of specific immunity in atherosclerosis. In Approche biologique de l'insuffisance cardiaque. Am Heart J 138:438-443.
51.Mouthon L., Nicoletti A., Lacroix-Desmazes S., Kaveri S., 63.Hinglais N., Heudes D., Nicoletti A., Mandet C., Laurent
and Kazatchkine M. D. 1999. Mécanismes d'action des M., Bariety J., and Michel J. B. 1994. Colocalization of immunoglobulines intraveineuses (IgIV). Sang Thrombose
myocardial fibrosis and inflammatory cells in rats. Lab
Vaisseaux 11:52-59.
Invest 70:286-294.


13_chapter_machalak et al_01.10.2006.doc

Chapter 13 ________________________________________________________________________ Quality of life impairment in bipolar disorder Erin E Michalak1, Greg Murray2, Allan H Young1 and Raymond W Lam1 1Department of Psychiatry, University of British Columbia 2Faculty of Life and Social Sciences, Swinburne University of Technology This chapter will present an overview of what is currently

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