Loïc Dupré PhD, Molecular and Cellular Immunology

Course and current status

Apr 2023 – today :  Visiting Researcher

Medical University of Vienna (Austria)

Molecular and clinical immunology of actin related immunodeficiencies 

Jun 2016 – Mar 2023 :  Visiting Researcher

Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases Vienna (Austria)

Molecular and clinical immunology

Feb 2010 – today :  Permanent researcher (DR2 INSERM since Dec 2022)

INFINITy / Toulouse Institute for Infectious and Inflammatory Diseases (France)

Lymphocyte biology in health, disease and therapy, Cell motility, Actin cytoskeleton

Feb 2006 – Jan 2010 :  European Excellence Team Leader

CPTP / Center for Physio-pathology of Toulouse Purpan (France)

Actin cytoskeleton, Primary immunodeficiencies  

Apr 2002 – Jan 2006 :  Project leader and staff member

San Raffaele Telethon Institute for Gene Therapy, HSR-TIGET, Milan (Italy)

Gene therapy approaches for Wiskott-Aldrich syndrome

Feb 1999 - Mar 2002 :  Post-doctoral fellow (recipient of a Marie-Curie fellowship)

San Raffaele Telethon Institute for Gene Therapy, HSR-TIGET, Milan (Italy)

Gene therapy approaches for Wiskott-Aldrich syndrome

Oct 1994 - Dec 1998 :  PhD student Institut Pasteur de Lille (France)

DNA vaccination strategies against Schistosomiasis

Jun - Aug 1996 :  Summer course Woods Hole, MA (USA)

Biology of parasitism

Mar - Sep 1993 :  Research assistant British Biotechnology Ltd, Oxford (UK)

Immunological properties of ß2-microglobulin/HIVgp120 fusion proteins

 

Contribution to Science (selected references):

1- Gene therapy approaches for the treatment of primary immunodeficiencies

Dupré, L., Trifari, S., Follenzi, A., Marangoni, F., Lain de Lera, T., Bernad, A., Martino, S., Tsuchiya, S., Bordignon, C., Naldini, L., Aiuti, A., and Roncarolo, M.-G. (2004). Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction. Mol. Ther. 10, 903-915.

Dupré, L.,* Marangoni, F.,* Scaramuzza, S., Trifari, S., Jofra-Hernández, R., Aiuti, A., Naldini, L., and Roncarolo, M.-G (2006). Efficacy of gene therapy for Wiskott-Aldrich syndrome using a WAS promoter/cDNA containing-lentiviral vector and non-lethal irradiation. Hum. Gene Ther. 17, 303-313. *Equal contribution authors. 

Charrier, S.,* Dupré, L.,* Scaramuzza, S.,* Jeanson-Leh, L., Blundell, M., Danos, O., Cattaneo, F., Aiuti, A., Eckenberg, R., Thrasher, A., Roncarolo, M.G., and Galy, A (2007). Lentiviral vectors targeting WASp expression to hematopoietic cells efficiently transduce CD34⁺ cells and correct cells from WAS patients. Gene Ther. 14, 415. *Equal contribution authors.

Magnani A*, Semeraro M*, Adam F, Booth C, Dupré L, Morris EC, Gabrion A, Roudaut C, Borgel D, Toubert A, Clave E, Abdo C, Gorochov G, Petermann R, Guiot M, Miyara M, Moshous D, Magrin E, Denis A, Suarez F, Lagresle C, Roche AM, Everett J, Trinquand A, Guisset M, Xu-Bayford J, Hacein-Bey-Abina S, Kauskot A, Elfeky R, Rivat C, Abbas S, Gaspar HB, Macintyre E, Picard C, Bushman FD, Galy A, Fischer A*, Six E*, Thrasher AJ* & Cavazzana M*. Long-term Outcome After Lentiviral Hematopoietic Stem/Progenitor Cell Gene Therapy for Wiskott-Aldrich Syndrome. Nat Med, 2022, 28:71-80. *Equal contribution authors.

2- Patho-mechanisms underlying primary immunodeficiencies

Dupré, L., Aiuti, A., Trifari, S., Martino, S., Saracco, P., Bordignon, C., and Roncarolo, M.-G. (2002). Wiskott-Aldrich syndrome protein regulates lipid raft dynamics during immunological synapse formation. Immunity 17, 157-166.

Marangoni F, Trifari S, Scaramuzza S, Panaroni C, Martino S, Notarangelo LD, Baz Z, Metin A, Cattaneo F, Villa A, Aiuti A, Battaglia M, Roncarolo M-G and Dupré L. WASP regulates suppressor activity of human and murine CD4⁺CD25⁺Foxp3⁺ natural regulatory T cells. J. Exp. Med. (2007) 204, 369.

Trifari S, Scaramuzza S, Catucci M, Ponzoni M, Mollica L, Chiesa R, Cattaneo F, Lafouresse F, Calvez R, Vermi W, Medicina D, Castiello MC, Marangoni F, Bosticardo M, Doglioni C, Caniglia M, Aiuti A, Villa A, Roncarolo MG, and Dupré L. Revertant T lymphocytes in a patient with Wiskott-Aldrich syndrome: Analysis of function and distribution in lymphoid organs. J. Allergy Clin. Immunol. (2010) 125, 439-448.

Pfajfer L*, Seidel MG*, Houmadi R, Rey-Barroso J, Hirschmugl T, Salzer E, Antón IM, Urban C, Schwinger W, Boztug K*, and Dupré L*. 2017. WIP deficiency severely affects human lymphocyte architecture during migration and synapse assembly. Blood. 130:1949-1953. *Equal contribution authors.

Pfajfer L*, Mair NK*, Jiménez-Heredia R, Genel F, Gulez N, Ardeniz Ö, Hoeger B, Köstel Bal S, Madritsch C, Kalinichenko A, Chandra Ardy R, Gerçeker B, Rey-Barroso J, Ijspeert H, Tangye SG, Simonitsch-Klupp I, Huppa JB, van der Burg M, Dupre L* & Boztug K*. Mutations affecting the actin regulator WDR1 lead to aberrant lymphoid immunity. J Allergy Clin Immunol, 2018,142:1589-1604. *Equal contribution authors.

Brigida I, Zoccolillo M, Cicalese MP, Pfajfer L, Barzaghi F, Scala S, Oleaga-Quintas C, Álvarez-Álvarez JA, Sereni L, Giannelli S, Sartirana C, Dionisio F, Pavesi L, Benavides-Nieto M, Basso-Ricci L, Capasso P, Mazzi B, Rosain J, Marcus N, Lee YN, Somech R, Degano M, Raiola G, Caorsi R, Picco P, Moncada Velez M, Khourieh J, Arias AA, Bousfiha A, Issekutz T, Issekutz A, Boisson B, Dobbs K, Villa A, Lombardo A, Neven B, Moshous D, Casanova JL, Franco JL, Notarangelo LD, Scielzo C, Volpi S, Dupre L, Bustamante J, Gattorno M & Aiuti A. T cell defects in patients with ARPC1B germline mutations account for their combined immunodeficiency. Blood, 2018,132:2362-2374.

Salzer E, Zoghi S, Kiss MG, Kage F, Rashkova C, Stahnke S, Haimel M, Platzer R, Caldera M, Chandra Ardy R, Höger B, Block J, Medgyesi D, Kain R, Ziaee V, Hammerl P, Bock C, Shahkarami S, Menche J, Dupré L, Huppa JB, Sixt M, Lomakin A, Rottner K, Binder CJ, Stradal TEB, Rezaei N & Boztug K. The cytoskeletal regulator HEM1 governs B-cell development and prevents autoimmunity. Science Immunology, 2020, 5:eabc3979.

Kalinichenko A, Perinetti Casoni G*, Dupré L*, Trotta L*, Huemer J, Galgano D, German Y, Haladik B, Pazmandi J, Thian M, Yüce Petronczki Ö, Chiang SC, Taskinen M, Hekkala A, Kauppila S, Lindgren O, Tapiainen J, Kraakman MJ, Vettenranta K, Lomakin AJ, Saarela J, Seppänen MRJ, Bryceson YT & Boztug K. RhoG deficiency abrogates cytotoxicity of human lymphocytes and causes hemophagocytic lymphohistiocytosis. Blood, 2021, 137:2033-2045. *Equal contribution authors.

Block J, Rashkova C*, Castanon I*, Zoghi S, Platon J, Chandra Ardy R, Fujiwara M, Chaves B, Schoppmeyer R, van der Made C, Jimenez Heredia R, Harms F.L, Alavi S, Alsina L, Sanchez Moreno P, Ávila Polo R, Cabrera-Pérez R, Köstel Bal S, Pfajfer L, Ransmayr B, Mautner A-K, Kondo R, Tinnacher A, Caldera M, Schuster M, Dominguez Conde C, Platzer R, Salzer E, Boyer T, Brunner H.G, Nooitgedagt-Frons J.E, Iglesias Jiménez E, Deyà-Martinez A, Camacho Lovillo M, Menche J, Bock C, Huppa J.B, Pickl W.F, Distel M, Yoder J.A, Traver D, Engelhardt K.R, Linden T, Kager L, Hannich T, Hoischen A, Hambleton S, Illsinger S, Da Costa L, Kutsche K, Chavoshzadeh Z, van Buul J.D, Anton J, Calzada-Hernández J, Neth O, Viaud J, Nishikimi A, Dupré L, Boztug K. Systemic Inflammation and Normocytic Anemia in DOCK11 Deficiency. New Engl J Med, 2023. 389:527-39. *Equal contribution authors.

3- Mechanisms governing leukemic cell motility

Malet-Engra, G., J. Viaud, L. Ysebaert, M. Farce, F. Lafouresse, G. Laurent, F. Gaits-Iacovoni, G. Scita, and L. Dupre. 2013. CIP4 controls CCL19-driven cell steering and chemotaxis in chronic lymphocytic leukemia. Cancer Res 73:3412-3424.

Malet-Engra G, Yu W, Oldani A, Rey-Barroso J, Gov NS, Scita G*, and Dupre L*. 2015. Collective cell motility promotes chemotactic prowess and resistance to chemorepulsion. Curr Biol 25:242-250. *Equal contribution authors.

Rey-Barroso J, Munaretto A, Rouquié N, Mougel A, Chassan M, Gadat S, Dewingle O, Poincloux R, Cadot S, Ysebaert L, Quillet-Mary A & Dupré L. Lymphocyte migration and retention properties affected by ibrutinib in chronic lymphocytic leukemia. Haematologica, 2024. 109:809-823.

4- Basic rules of human T cell motility and cytotoxic function 

Vasconcelos, Z., S. Müller, D. Guipouy, Y. Wong, C. Christophe, S. Gadat, S. Valitutti* and L. Dupré*. 2015. Individual human cytotoxic T lymphocytes exhibit intraclonal heterogeneity during sustained killing. Cell Reports. 11:1474-1485. *Equal contribution authors.

Houmadi R, Guipouy D, Rey-Barroso J, Vasconcelos Z, Cornet J, Manghi M, Destainville N, Valitutti S, Allart S, Dupré L. 2018. The Wiskott-Aldrich Syndrome Protein Contributes to the Assembly of the LFA-1 Nanocluster Belt at the Lytic Synapse. Cell Reports. 22:979-991.

German Y*, Vulliard L*, Kamnev A, Pfajfer L, Huemer J, Mautner A-K, Rubio A, Kalinichenko A, Boztug K, Ferrand A, Menche J & Dupré L. Morphological profiling of human T and NK lymphocytes by high-content cell imaging. Cell Reports. 2021, 36:109318.

Lacouture C, Chaves B, Guipouy D, Houmadi R, Duplan-Eche V, Allart S, Destainville N & Dupré L. LFA-1 nanoclusters integrate TCR stimulation strength to tune T-cell cytotoxic activity. Nature Communications, 2024, 15:407.

Kamnev A*, Mehta T*, Wielscher M, Chaves B, Lacouture C, Mautner A-K, Shaw L-E, Caldera M, Menche J, Weninger W-P, Farlik M, Boztug K & Dupré L. Coordinated ARP2/3 and glycolytic activities regulate the morphological and functional fitness of human CD8⁺ T cells. Cell Reports. 2024 43:113853.

Scientific summary

The driving force of my career is a deep motivation to combine basic research with applied research dedicated to the improvement of health. During my PhD thesis (1994-1998, Pasteur Institute, Lille), I developed a DNA vaccination approach against the parasite Schistosoma mansoni. As post-doctoral fellow and project leader (1999-2006, San Raffaele Telethon Institute for Gene Therapy, Milan), I set up gene therapy approaches for the treatment of inborn errors of immunity. My major contribution has been to initiate and successfully implement a gene therapy program for the treatment of the Wiskott-Aldrich syndrome. Since the establishment of my research group in 2006 at the Toulouse Institute for Infectious and Inflammatory Diseases (INFINITy), I have specialized in deciphering the molecular regulation of actin cytoskeleton dynamics in the contact of human T cell migration, immunological synapse assembly and cytotoxic activity. My research activity aims at deciphering novel layers of T cell function regulation and to exploit the generated knowledge to decipher the pathomechanisms of complex diseases (inborn errors of immunity, inflammatory diseases) and to optimize T cell-based immunotherapies (CAR-T cells).