Fabio Candotti

Fabio Candotti
MD, Associate Professor of Medicine and Head Physicien

Education:
October 1987: Medical Degree, University of Brescia, Italy

Specialty Certification:
October 1996: Pediatric Allergy and Immunology Subspecialty Board, University of Brescia, Italy
June 1992: Pediatrics Specialty Board, University of Pavia, Italy

Postgraduate Training:
1994 – 1996: Postdoctoral Fellow, Clinical Gene Therapy Branch, NHGRI, NIH, Bethesda, MD, USA
1992 – 1994: Postdoctoral Fellow, Metabolism Branch, NCI, NIH, Bethesda, MD, USA
1991 – 1992: Postdoctoral Fellow, Laboratory of Biotechnology, University of Brescia, Italy

Faculty Appointments:
2014 – present: Associate Professor of Medicine, School of Medicine and Biology, University of Lausanne, Switzerland
2004 – 2014: Senior Investigator (tenured), NHGRI, NIH, Bethesda, MD, USA
1998 – 2004: Investigator (tenure-track), NHGRI, NIH, Bethesda, MD, USA
1996 – 1997: Assistant Professor, Department of Pediatrics, University of Brescia, Italy

Medical Appointments:
2017 – present: Head Physician, Division of Immunology and Allergy, CHUV, Lausanne, Switzerland
2014 – 2017: Attending Physician, Division of Immunology and Allergy, CHUV, Lausanne, Switzerland
1998 – 2014: Attending Physician, Clinical Center, NIH, Bethesda, MD, USA
1988 – 1989: Medical Second Lieutenant, Italian Customs Service Academy, Bergamo, Italy
1996 – 1997: Attending Physician, Department of Pediatrics, Brescia City Hospital, Italy

Selected Academic Administrative Appointments:
2016 – present: Chair Scientific Committee, Master in advanced Studies in Vaccinology (IMVACC), University of Lausanne, Switzerland
2014 – present: Director, Vaccine and Immunotherapy Center, CHUV, Lausanne, Switzerland
2006 – 2014: Chair, NHGRI/NIH Institutional Review Board

Selected Scientific Activity in Academic Societies:
American Society of Gene Therapy (ASGT)

  • Member, Board of Directors,2010-2013
  • Chair, Committee on Gene & Cell Therapy of Genetic & Metabolic Diseases, 2009-10

Clinical Immunology Society (CIS)

  • Chair, Membership Committee, 2006-2009

American Society of Hematology

  • Chair, Immunology and Host Defense Scientific Committee (2012)

European Society for Immunodeficiencies (ESID)

  • Treasurer and Member, Executive Committee (2016-2020)

 

Selected Original Peer-reviewed Articles (out of 120):

  1. Macchi P., Villa A., Giliani S., Sacco M.G., Frattini A., Porta F., Ugazio A.G., Johnston J.A., Candotti F., O'Shea J.J., Vezzoni P., Notarangelo L.D.: Mutations of Jak-3 gene in patients with autosomal severe combined immune deficiency (SCID). Nature 1995; 377:65-68.
  2. Candotti F., Johnston J.A., Puck J.M., Sugamura K., O'Shea J.J., Blaese R.M.: Retroviral-mediated gene correction for X-linked severe combined immunodeficiency (XSCID). Blood 1996; 87:3097-3102.
  3. Candotti F., Oakes S.A., Johnston J.A., Notarangelo L.D., O’Shea J.J., Blaese R.M.: In vitro correction of JAK3-deficient severe combined immunodeficiency by retroviral-mediated gene transduction. J Exp Med 1996; 183:2687-2692.
  4. Oakes S.A.*, Candotti F.*, Johnston J.A., Chen Y-Q, Ryan J, Taylor N., Liu X., Hennighausen L., Notarangelo L.D., Paul W.E., Blaese R.M., O’Shea J.J.: Signaling via IL-2 and IL-4 in JAK3-deficient severe combined immunodeficiency lymphocytes: JAK3 dependent and -independent pathways. Immunity 1996; 5:605-615. *Co-first authors
  5. Taylor N., Candotti F., Smith S., Oakes S.A., Isakov J., Jahn T., Puck J.M., O’Shea J.J., Weinberg K., Johnston J.A.: IL-4-induced signaling in B lymphocytes from patients with X-linked severe combined immunodeficiency. J Biol Chem 1997; 272:7314-7327.
  6. Candotti F.,. Oakes S.A, Johnston J.A., Giliani S., Mella P., Schumacher R.F., Badolato R., Ugazio A.G., Notarangelo L.D., Bozzi F., Macchi P., Mapelli E., Vezzoni P., Blaese R.M., O’Shea J.J., Villa A.: Structural and functional basis of JAK3-deficient severe combined immunodeficiency. Blood 1997; 90:3996-4003.
  7. Bozzi F., Lefranc G., Villa A., Badolato R., Schumacher R.F., Khalil G., Loiselet J., Bresciani S., O'Shea J.J., Vezzoni P., Notarangelo L.D., Candotti F. : Molecular and biochemical characterization of JAK3 deficiency in a patient with severe combined immunodeficiency over 20 years after bone marrow transplantation: implications for treatment. Br J Haematol 1998; 102:1363-1366
  8. Candotti F., L., Facchetti F., Blanzuoli L., Stewart D.M., Nelson L.D., Blaese R.M.: Retroviral-mediated WASP gene transfer corrects defective actin polymerization in B-cell lines from Wiskott-Aldrich syndrome patients carrying "null" mutations. Gene Ther, 1999; 6:1170-1174
  9. Otsu M., Anderson S.M., Bodine D.M., Puck J.M., O’Shea J.J, Candotti F.: Lymphoid development and function in X-linked severe combined immunodeficiency mice after stem cell gene therapy. Mol Ther, 2000; 1:145-153
  10. Chinnasamy D., Chinnasamy N., Enriquez M.J., Otsu M., Morgan R.A., Candotti F.: Lentiviral-mediated gene transfer into human lymphocytes: role of HIV-1 accessory proteins. Blood, 2000; 96:1309-1316
  11. Otsu M., Sugamura K., Candotti F.: In vivo competition studies between normal and common g chain-defective bone marrow cells: implications for gene therapy.  Hum Gene Ther, 2000; 11:2051-2056
  12. Otsu M., Sugamura K., Candotti F.: Lack of dominant-negative effects of a truncated gc on retroviral-mediated gene correction of immunodeficient mice.  Blood, 2001; 97:1618-1624
  13. Wada T., Schurman S.H., Garabedian E.K., Ochs H.D., Nelson D.L., Candotti F.: Somatic mosaicism in Wiskott-Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism. Proc Natl Acad Sci USA, 2001; 98(15):8697-702
  14. Frucht D.M., Gadina M., Jagadeesh G.J., Aksentijevich I., Takada K., Bleesing J.J.H, Nelson J., Muul L.M., Perham G., Morgan G., Gerritsen E.J.A., Schumacher R.F., Mella P., Veys P.A., Fleisher T.A., Kaminski E.R., Notarangelo L.D., O'Shea J.J., Candotti F.: Unexpected and variable phenotypes in a family with JAK3 deficiency.  Genes Immun, 2001; 2(8):422-432
  15. Otsu M., Hershfield M.S., Tuschong L.M., Muul L.M., Onodera M., Ariga T., Sakiyama Y., Candotti F.: Flow Cytometry Analysis of Adenosine Deaminase (ADA) Expression: A Simple and Reliable Tool for the Assessment of ADA-Deficient Patients Before and After Gene Therapy. Hum Gene Ther, 2002; 13:425-432
  16. Wada T., Jagadeesh G.J., Nelson L.D., Candotti F.: Retrovirus-mediated WASP gene transfer corrects Wiskott-Aldrich syndrome T cell dysfunction. Hum Gene Ther, 2002;13:1039-1046
  17. Muul L.M., Tuschong L.M., Soenen S.L., Jagadeesh G.J., Ramsey W.J., Long Z., Carter C.S., Garabedian E.K., Alleyne M., Brown M., Bernstein W., Schurman S.H., Fleisher T.A., Leitman S.F., Dunbar C.E., Blaese R.M., Candotti F.: Persistence and expression of the adenosine deaminase gene for twelve years and immune reaction to gene transfer components: Long-term results of the first clinical gene therapy trial. Blood 2003; 101:2563-2569.
  18. Wada T., Konno A., Schurman S.H., Garabedian E.K., Anderson S.M., Kirby M., Nelson D.L., Candotti F.: Second-site mutation in the Wiskott-Aldrich syndrome (WAS) protein gene causes somatic mosaicism in two WAS siblings.  J Clin Invest 2003, 111:1389-1397.
  19. Konno A., Wada T., Schurman S.H., Garabedian E.K., Kirby M., Anderson S.M., Candotti F.: Differential contribution of Wiskott-Aldrich syndrome protein to selective advantage in T and B cell lineages.  Blood 2004; 103:676-678.
  20. Bosticardo M., Witte I., Fieschi C., Novelli F., Casanova J.L., Candotti F.: Retroviral-Mediated Gene Transfer Restores IL-12 and IL-23 Signaling Pathways in T Cells from IL-12 Receptor b1 Deficient Patients.  Mol Ther 2004; 9:895-901.
  21. Wada T., Schurman S.H., Jagadeesh G.J., Garabedian E.K., Nelson D.L., Candotti F.: Multiple patients with revertant mosaicism in a single Wiskott-Aldrich syndrome family.  Blood 2004; 104:1270-1272.
  22. Wada T., Schurman S.H., Garabedian E.K., Yachie A., Candotti F.: Analysis of T-cell repertoire diversity in Wiskott-Aldrich syndrome.  Blood 2005; 106:3895-3897.
  23. Engel B.C., Podsakoff G.M., Ireland J.L., Smogorzewska M., Carbonaro D.A., Wilson K., Shah A., Kapoor N., Sweeney M., Borchert M., Crooks G.M., Weinberg K.I., Parkman R., Rosenblatt H., Wu S-Q, Hershfield M.S., Candotti F., Kohn D.B.: Prolonged pancytopenia in a gene therapy patient with ADA-deficient SCID and trisomy 8 mosaicism – A case report. Blood 2007; 109:503-506.
  24. Konno A., Kirby M., Anderson S.A., Schwartzberg P.L., Candotti F.: The Expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein, WIP.  Int Immunol 2007; 19:185-92.
  25. Adriani M., Aoki J., Horai R., Thornton A.M., Konno A., Kirby M., Anderson S.M., Siegel R.M., Candotti F., Schwartzberg P.L.: Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome. Clin Immunol, 2007; 124:41-8.
  26. Lagresle-Peyrou C., Six E.M., Picard C., Rieux-Laucat F., Michel V., Ditadi A., Demerens-de Chappedelaine C., Morillon E., Valensi F., Simon-Stoos K.L., Mullikin J.C., Noroski L.M., Besse C., Wulffraat N.M., Ferster A., Abecasis M.M., Calvo F., Petit C., Candotti F., Abel L., Fischer A., Cavazzana-Calvo M.: Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness. Nat Genet 2009; 41:106-11. [PMID: 19043416; PMCID: PMC2612090]
  27. Bosticardo M., Ghosh A., Du Y., Jenkins N.A., Copeland N.G., Candotti F.: Self-inactivating retroviral vector-mediated gene transfer induces oncogene activation and immortalization of primary murine bone marrow cells.  Mol Ther 2009; 17:1910-8. [PMID: 19638958; PMCID: PMC2835037]
  28. Davis B.R., Yan Q., Bui J.H., Felix K., Moratto D., Muul L.M., Prokopishyn N.L., Blaese R.M., Candotti F.: Somatic Mosaicism in the Wiskott-Aldrich Syndrome: Molecular and Functional Characterization of Genotypic Revertants.  Clin Immunol 2010; 135:72-83. [PMID: 20123155; NIHMSID: 176191]
  29. Taylor M.D., Sadhukhan S., Ramgopal A., Kottangada P., Sarkar K., D’Silva S., Selvakumar A., Candotti F., and Vyas Y.M.: Nuclear Role of WASp in the Pathogenesis of Dysregulated TH1-Immunity in Human Wiskott-Aldrich Syndrome. Sci Transl Med 2010; 2:37ra44. [PMID: 20574068; PMCID: PMC2943146]
  30. Adriani M., Jones K.A., Uchiyama T., Kirby M., Silvin C., Anderson S., Candotti F.: Defective inhibition of B-cell proliferation by Wiskott-Aldrich syndrome protein-deficient regulatory T cells.  Blood 2011; 117:6608-11. [PMID: 21515824; PMCID: PMC3123025]
  31. Sokolic R., Maric I., Kesserwan C., Garabedian E., Hanson C.I., Dodds M., Buckley R., Issekutz A., Kamani N., Shaw K., Tan B., Bali P., Hershfield M.S., Kohn D.B., Wayne A.S., Candotti F.: Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency.  Blood 2011; 118:2688-94. [PMID: 21725047; PMCID: PMC3172788]
  32. Shimizu M., Nikolov N.P., Ueno K., Ohta K., Siegel R.M., Yachie A., Candotti F.: Development of IgA nephropathy-like glomerulonephritis associated with Wiskott-Aldrich syndrome protein deficiency.  Clin Immunol 2012; 142:160-6. [PMID: 22079330; PMCID: PMC3273668]
  33. KesserwanC., SokolicR., Cowen E.W., GarabedianE.K., Heselmeyer-HaddadK., Lee C.R., PittalugaS., OrtizC., BairdK., Lopez-TerradaD., BridgeJ.A., WayneA.S., CandottiF.: Multicentric dermatofibrosarcoma protuberans in patients with adenosine deaminase-deficient severe combined immune deficiency. J Allergy Clin Immunol 2012; 129:762-9. [PMID: 22153773; PMCID: PMC3294021]
  34. Uchiyama T., Adriani M., Jagadeesh G.J., Paine A., Candotti F.: Foamy virus vector-mediated gene correction of a mouse model of Wiskott-Aldrich syndrome. Mol Ther 2012; 20:1270-9. [PMID: 22215016; PMCID: PMC3369282]
  35. Candotti F., Shaw K.L., Muul L., Carbonaro D., Sokolic R., Choi C., Schurman S.H., Garabedian E., KesserwanC., Jagadeesh G.J., Fu P-Y., Gschweng E., Cooper A., Tisdale J.F., Weinberg K.I., Crooks G.M., Kapoor N., Shah A., Abdel-Azim H., Yu X-J., Smogorzewska M., Wayne A.S., Rosenblatt H.M., Davis C.M., Hanson C., Rishi R.G., Wang X., Gjertson D., Yang O.O., Balamurugan A., Bauer G., Ireland J.A., Engel B.C., Podsakoff G.M., Hershfield M.S., Blaese R.M., Parkman R., Kohn D.B: Gene Therapy for Adenosine Deaminase-Deficient Severe Combined Immune Deficiency: Clinical Comparison of Retroviral Vectors and Treatment Plans.  Blood 2012; 120:3635-46. [PMID: 22968453; PMCID: PMC3488882]
  36. Simon K.L., Anderson S.A., Garabedian E.K., Moratto, D., Sokolic R.A., Candotti F.: Molecular and phenotypic abnormalities of B lymphocytes in patients with Wiskott-Aldrich syndrome. J Allergy Clin Immunol 2014, 133(3):896-899. [PMID: 24210885 – PMCID: PMC3943658]
  37. Sadhukhan S., Sarkar K., Taylor M., Candotti F., Vyas Y.M.: Nuclear role of WASp in gene transcription is uncoupled from its ARP2/3-dependent cytoplasmic role in actin polymerization. J Immunol 2014, 193(1):150-60. [PMID: 24872192 - PMC Journal - In Process]
  38. Ikawa Y., Hess R.A., Dorward H., Cullinane A.R., Huizing M., Gochuico B.R., Gahl W.A., Candotti F.: In vitro functional correction of Hermansky-Pudlak Syndrome.  Mol Genet Metabol 2015, 114:62-5. [PMID: 25468649; PMC MSID: 25468649]
  39. Rissone A., Weinacht K.G., la Marca G., Bishop, Giocaliere E., Jagadeesh J.G., Felgentreff K., Dobbs K., Al-Herz W., Jones M., Chandrasekharappa S., Kirby M.R., Wincovitch S., Karen S., Itan Y., DeVine A., Schlaeger T., Schambach A., Sood R., Notarangelo L.D., Candotti F.: Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress.  J Exp Med 2015, 212(8):1185-202. [PMID 26150473]
  40. Volpi S., Santori E., Abernethy K., Mizui M., Dahlberg C.I.M., Recher M., Capuder K., Csizmadia E., Ryan D., Mathew D., Tsokos G.C., Snapper S., Westerberg L.S., Thrasher A.J., Candotti F., Notarangelo L.D.: N-WASP is required for B cell-mediated autoimmunity in the Wiskott-Aldrich syndrome.  Blood 2015 ;127(2):216-20. [PMID: 26468226]
  41. Ikawa Y., Uchiyama T., Jagadeesh J., Candotti F.: The long terminal repeat negative control region is a critical element for insertional oncogenesis after gene transfer into hematopoietic progenitors with Moloney murine leukemia viral vectors.  Gene Ther 2016, 23(11):815-8. [PMID: 27487944]
  42. Cooper A.R., Lill G.R., Shaw K., Carbonaro D., Davila A., Sokolic R., Candotti F., Pellegrini M., Kohn D.B.: Cytoreductive conditioning intensity predicts clonal diversity in ADA-SCID retroviral gene therapy patients. Blood 2017; 129(19):2624-2635. [PMID: 28351939]
  43. Shaw K.L., Garabedian E., Mishra S., Barman P., Davila A., Carbonaro D.,X., de Oliveira S., Choi Y., Ikeda A., Terrazas D., Fu P.Y., Yu A., Fernandez B.C., Cooper A.R., Engel B., Podsakoff G., Balamurugan A,. Anderson S., Muul L., Jagadeesh G.J., Kapoor N., Tse J., Moore T.B., Purdy K., Rishi R., Mohan K., Skoda-Smith S., Buchbinder D., Abraham R.S., Scharenberg A., Yang O.O., Cornetta K., Gjertson D., Hershfield M., Sokolic R., Candotti F., Kohn D.B.: Clinical efficacy of gene-modified stem cells in adenosine deaminase-deficient immunodeficiency. J Clin Invest 2017, 127(5):1689-1699. [PMID: 28346229]
 Dernière mise à jour le 09/09/2019 à 15:48