Download curriculum vitae 顧 正 崙

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CURRICULUM VITAE
顧 正 崙
Cheng-Lung KU, Ph. D
Assistant professor,
Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan
Adjunct assistant professor,
Graduate Institute of Clinical Medical Science, China Medical University, Taiwan,
Contact:
259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan, 333, R.O.C.
Tel: (886) (03)211-880 ext 3896
Mobile: 0933650723
Email: [email protected]
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EDUCATION
2007
Ph. D.
2000
Master Degree

PROFESSIONAL EXPERIENCE
2010
Assistant professor
Graduate Institute of Clinical Medical Science,
Chang-Gung University, Taoyuan, Taiwan
Adjunct assistant professor Graduate Institute of Clinical Medical Science, China
2011
2008-2010

Université Paris V René Descartes, Doctoral.
INSERM U550 Paris, France.
Institute of Microbiology and Immunology,
Faculty of life science, National Yang-Ming
University, Taipei, Taiwan
Assistant professor
Medical University, Taichung, Taiwan
Graduate Institute of Clinical Medical Science, China
Medical University, Taichung, Taiwan
FIELD OF INTERESTS
Human Immunology
Human genetic infectious disease
Primary immunodeficiency
Autoimmune and infection disease
Ku, C.L.
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
HONORS

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Keystone Symposia Global Health Travel Award, funding by Bill & Melinda Gates Foundation
(2013).
Ph.D. fellowship from the French ministry of foreign affairs (2001).

CURRENT RESEARCH TOPICS
1. Autoantibodies against Interferon- in adults with severe mycobacterial infection
Severe infections caused by less virulent nontuberculous mycobacterium (NTM) are always found
acquired immunodeficiency syndrome patients and in primary immunodeficiency children with
genetic defect in IFN--IL-12/23 circuit. In adult, the prevalence of mycobacterial infections is
increasing with ages; however, the molecular basis of the susceptibility is largely unknown.
Acquired functional impairment or genetic variants in these pathways might diminish host immune
system and cause the predispose to mycobacterial infection in adult, and they couldn’t be diagnosed
by clinical routine examination. We have found around 50 patients with disseminated mycobacterial
infections who have high affinity, naturally occurred autoantibodies against IFN-. Patients with
autoantibodies to different cytokines have been found recently and were predispose to infectious
diseases. In literature, autoantibodies to IFN- had found in some patients with disseminated
NTM and TB infection world-wide. Compared with previous reports, our patients have a specific
and very narrow clinical manifestation: 1: high coincident with reactivation of varicella-zoster virus
(VZV) and salmonella species infections. 2: no clinical autoimmune phenotype and no other
autoantibodies observed. 3: high prevalence of presence of anti-IFN- autoantibodies in our
mycobacterial infection patients recruited. Therefore, we plan to address the role of anti-cytokines
autoantibodies in adult mycobacterial infection, and using this particular cohort to study the role of
IFN- in immune system and infectious diseases in natural.
We listed some ongoing studying:


“Anti-IFN-γ Autoantibody-Mediated Mycobacterial Disease is Strongly Associated with HLADR*15:02/16:02 and -DQ*05:01/05:02 in Patients from South East Asia.” We conducted an
international survey with other laboratories. We confirmed the association of DRB1*16:02 and
DQB1*05:02 in patients from other regions and we also identified a new risk allele
DRB1*15:02- DQB1*05:01 in Thai population.
“ Clinical Manifestations, Courses, and Outcomes in 45 Patients with Anti-Interferon-γ
Autoantibodies and Disseminated Non-Tuberculous Mycobacterial Infections.

“Role of Anti-IFN-γ Autoantibody in TB infection”
2. Molecular Mechanism of Anti-IFN- Autoantibodies Disease
We are interested in studying the molecular basis of development of anti-IFN- autoantibodies
among patients with severe NTM infections and keen to develop a novel therapeutic strategy based
on the molecular mechanisms of these autoantibodies. In this project, we aim to clarify if the
development of anti-IFN- autoantibody is induced by “mimicry molecule” mechanism and to
Ku, C.L.
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establish a proof of principle alternative therapeutic strategy to anti-IFN- autoantibodies and other
Anticytokine autoantibodies diseases. In our preliminary data, we identified a shared and critical B
cell epitope of anti-IFN-γ autoantibodies in patients and raised a molecular mimicry model that the
production of anti-IFN-γ autoantibodies was triggered by a microbe protein.
3. Role of Innate Immunity Against Enterovirus infection in human.
The enteroviruses are a genus of (+) single-strained RNA viruses associated with several human and
mammalian diseases. EV71 infection is endemic in Taiwan and caused threat to the health of
children. Toll-like receptors (TLRs) is a proto-type PRRs and there are 10 TLRs found in human
which could recognize various molecules associated with most pathogens. They acted as the sensor
for the microbial infection and the activated TLRs played critical role in host immune system in face
of virus. The function of TLRs against viral infection is confirmed by the discovered of human
TLR3 deficient patients who suffered from severe HSV encephalitis. Moreover, TRAF3, TRIF,
TBK1 and UNC-93B are molecules associated with TLR3signaling, the defects of these two genes
in human were also found to associate with severe HSV encephalitis. This is also a
proof-of-principle studying that severe viral infection might be caused by the genetic mutation in
innate immunity. Clinically, the severe EV71 would manifest the encephalitis or even progress to
cardiopulmonary collapse. We hypothesize that patients with the genetic defect or variant in TLR3
or other PRRs pathways which might cause the lack of appropriated immune response might have
more severe clinical manifestation in compared with normal patients infected by EV71. In
preliminary data, we had found three patients with TLR3 deficiency in children with CNS-involved
EV71 infection and we are currently studying the impact of these mutation. However, we had
applied the whole exomic sequencing to search new morbid genes in 7 children with CNS-involved
EV71 infection.
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LIST OF PUBLISHCATIONs
H-Index: 1726,27,24,25,18-23,14-17,10-13,8,9,6,7,5,1-4
*: first, co-first or corresponding author.
1.
Chi CY, Chu CC, Liu JP, Lin CH, Ho MW, Lo WJ, Lin PC, Chen HJ, Chou CH, Feng JY,
Fung CP, Sher YP, Li CY, Wang JH & *Ku CL. Anti-IFN-gamma autoantibodies in adults
with disseminated nontuberculous mycobacterial infections are associated with
HLA-DRB1*16:02 and HLA-DQB1*05:02 and the reactivation of latent varicella-zoster
2.
3.
virus infection. Blood. 2013, 121: 1357-1366.
Lee WI, Huang JL, Wu TS, Lee MH, Chen IJ, Yu KH, Liu CY, Yang CH, Hsieh MY, Lin YL,
Shih YF, Jaing TH, Huang SC, Kuo TT & Ku CL. Patients with inhibitory and neutralizing
auto-antibodies to interferon-gamma resemble the sporadic adult-onset phenotype of
Mendelian Susceptibility to Mycobacterial Disease (MSMD) lacking Bacille
Calmette-Guerin (BCG)-induced diseases. Immunobiology. 2013, 218: 762-771.
Lin CJ, Wang SC, Ku CL, Kao JK, Chen M & Liu CS. Successful Unrelated Cord Blood
Stem Cell Transplantation in an X-linked Chronic Granulomatous Disease Patient with
Disseminated BCG-induced Infection. Pediatrics and neonatology. 2013, (In press)
Ku, C.L.
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4.
Savolainen L, Kantele A, Sandboge B, Siren M, Valleala H, Tuompo R, Pusa L,
Erkinjuntti-Pekkanen R, Knuuttila A, Ku CL, Chi CY, Vasankari T & Tuuminen T.
Modification of Clearview Tuberculosis (TB) Enzyme-Linked Immunosorbent Assay for TB
5.
6.
Patients Not Infected with HIV. Clin. Vaccine Immunol. 2013, 20: 1479-1482.
Mahlaoui N, Minard-Colin V, Picard C, Bolze A, Ku CL, Tournilhac O, Gilbert-Dussardier B,
Pautard B, Durand P, Devictor D, Lachassinne E, Guillois B, Morin M, Gouraud F, Valensi F,
Fischer A, Puel A, Abel L, Bonnet D & Casanova JL. Isolated congenital asplenia: a French
nationwide retrospective survey of 20 cases. The Journal of pediatrics. 2011, 158: 142-148,
148 e141.
Picard C, von Bernuth H, Ghandil P, Chrabieh M, Levy O, Arkwright PD, McDonald D,
Geha RS, Takada H, Krause JC, Creech CB, Ku CL, Ehl S, Marodi L, Al-Muhsen S,
Al-Hajjar S, Al-Ghonaium A, Day-Good NK, Holland SM, Gallin JI, Chapel H, Speert DP,
Rodriguez-Gallego C, Colino E, Garty BZ, Roifman C, Hara T, Yoshikawa H, Nonoyama S,
Domachowske J, Issekutz AC, Tang M, Smart J, Zitnik SE, Hoarau C, Kumararatne DS,
Thrasher AJ, Davies EG, Bethune C, Sirvent N, de Ricaud D, Camcioglu Y, Vasconcelos J,
Guedes M, Vitor AB, Rodrigo C, Almazan F, Mendez M, Arostegui JI, Alsina L, Fortuny C,
Reichenbach J, Verbsky JW, Bossuyt X, Doffinger R, Abel L, Puel A & Casanova JL. Clinical
features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore).
7.
2010, 89: 403-425.
Wu WP, Chang CH, Chiu YT, Ku CL, Wen MC, Shu KH & Wu MJ. A reduction of unilateral
ureteral obstruction-induced renal fibrosis by a therapy combining valsartan with aliskiren.
8.
Am. J. Physiol. Renal Physiol. 2010, 299: F929-941.
Comeau JL, Lin TJ, Macken MB, Li B, Ku CL, von Bernuth H, Casanova JL & Issekutz AC.
Staphylococcal pericarditis, and liver and paratracheal abscesses as presentations in two new
9.
cases of interleukin-1 receptor associated kinase 4 deficiency. Pediatr. Infect. Dis. J. 2008, 27:
170-174.
von Bernuth H, Picard C, Jin Z, Pankla R, Xiao H, Ku CL, Chrabieh M, Mustapha IB,
Ghandil P, Camcioglu Y, Vasconcelos J, Sirvent N, Guedes M, Vitor AB, Herrero-Mata MJ,
Arostegui JI, Rodrigo C, Alsina L, Ruiz-Ortiz E, Juan M, Fortuny C, Yague J, Anton J, Pascal
M, Chang HH, Janniere L, Rose Y, Garty BZ, Chapel H, Issekutz A, Marodi L,
Rodriguez-Gallego C, Banchereau J, Abel L, Li X, Chaussabel D, Puel A & Casanova JL.
Pyogenic bacterial infections in humans with MyD88 deficiency. Science. 2008, 321:
691-696.
10.
11.
Ku, C.L.
Ku CL, Picard C, Erdos M, Jeurissen A, Bustamante J, Puel A, von Bernuth H, Filipe-Santos
O, Chang HH, Lawrence T, Raes M, Marodi L, Bossuyt X & Casanova JL. IRAK4 and
NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal
disease. J. Med. Genet. 2007, 44: 16-23.
Ku CL, von Bernuth H, Picard C, Zhang SY, Chang HH, Yang K, Chrabieh M, Issekutz AC,
Cunningham CK, Gallin J, Holland SM, Roifman C, Ehl S, Smart J, Tang M, Barrat FJ, Levy
O, McDonald D, Day-Good NK, Miller R, Takada H, Hara T, Al-Hajjar S, Al-Ghonaium A,
Speert D, Sanlaville D, Li X, Geissmann F, Vivier E, Marodi L, Garty BZ, Chapel H,
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Rodriguez-Gallego C, Bossuyt X, Abel L, Puel A & Casanova JL. Selective predisposition to
bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise
12.
13.
14.
15.
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redundant in protective immunity. J. Exp. Med. 2007, 204: 2407-2422.
Picard C, von Bernuth H, Ku CL, Yang K, Puel A & Casanova JL. Inherited human IRAK-4
deficiency: an update. Immunol. Res. 2007, 38: 347-352.
Zhang SY, Jouanguy E, Ugolini S, Smahi A, Elain G, Romero P, Segal D, Sancho-Shimizu V,
Lorenzo L, Puel A, Picard C, Chapgier A, Plancoulaine S, Titeux M, Cognet C, von Bernuth
H, Ku CL, Casrouge A, Zhang XX, Barreiro L, Leonard J, Hamilton C, Lebon P, Heron B,
Vallee L, Quintana-Murci L, Hovnanian A, Rozenberg F, Vivier E, Geissmann F, Tardieu M,
Abel L & Casanova JL. TLR3 deficiency in patients with herpes simplex encephalitis.
Science. 2007, 317: 1522-1527.
Cardenes M, von Bernuth H, Garcia-Saavedra A, Santiago E, Puel A, Ku CL, Emile JF,
Picard C, Casanova JL, Colino E, Bordes A, Garfia A & Rodriguez-Gallego C. Autosomal
recessive interleukin-1 receptor-associated kinase 4 deficiency in fourth-degree relatives. J.
Pediatr. 2006, 148: 549-551.
Filipe-Santos O, Bustamante J, Haverkamp MH, Vinolo E, Ku CL, Puel A, Frucht DM,
Christel K, von Bernuth H, Jouanguy E, Feinberg J, Durandy A, Senechal B, Chapgier A,
Vogt G, de Beaucoudrey L, Fieschi C, Picard C, Garfa M, Chemli J, Bejaoui M, Tsolia MN,
Kutukculer N, Plebani A, Notarangelo L, Bodemer C, Geissmann F, Israel A, Veron M,
Knackstedt M, Barbouche R, Abel L, Magdorf K, Gendrel D, Agou F, Holland SM &
Casanova JL. X-linked susceptibility to mycobacteria is caused by mutations in NEMO
impairing CD40-dependent IL-12 production. J. Exp. Med. 2006, 203: 1745-1759.
Puel A, Reichenbach J, Bustamante J, Ku CL, Feinberg J, Doffinger R, Bonnet M,
Filipe-Santos O, de Beaucoudrey L, Durandy A, Horneff G, Novelli F, Wahn V, Smahi A,
Israel A, Niehues T & Casanova JL. The NEMO mutation creating the most-upstream
premature stop codon is hypomorphic because of a reinitiation of translation. Am. J. Hum.
17.
Genet. 2006, 78: 691-701.
von Bernuth H, Ku CL, Rodriguez-Gallego C, Zhang S, Garty BZ, Marodi L, Chapel H,
Chrabieh M, Miller RL, Picard C, Puel A & Casanova JL. A fast procedure for the detection
18.
of defects in Toll-like receptor signaling. Pediatrics. 2006, 118: 2498-2503.
Ku CL, Dupuis-Girod S, Dittrich AM, Bustamante J, Santos OF, Schulze I, Bertrand Y,
Couly G, Bodemer C, Bossuyt X, Picard C & Casanova JL. NEMO mutations in 2 unrelated
19.
boys with severe infections and conical teeth. Pediatrics. 2005, 115: e615-619.
Ku CL, Yang K, Bustamante J, Puel A, von Bernuth H, Santos OF, Lawrence T, Chang HH,
Al-Mousa H, Picard C & Casanova JL. Inherited disorders of human Toll-like receptor
20.
signaling: immunological implications. Immunol. Rev. 2005, 203: 10-20.
Lawrence T, Puel A, Reichenbach J, Ku CL, Chapgier A, Renner E, Minard-Colin V,
Ouachee M & Casanova JL. Autosomal-dominant primary immunodeficiencies. Curr. Opin.
21.
Hematol. 2005, 12: 22-30.
Puel A, Yang K, Ku CL, von Bernuth H, Bustamante J, Santos OF, Lawrence T, Chang HH,
Al-Mousa H, Picard C & Casanova JL. Heritable defects of the human TLR signalling
Ku, C.L.
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pathways. J Endotoxin Res. 2005, 11: 220-224.
22.
von Bernuth H, Puel A, Ku CL, Yang K, Bustamante J, Chang HH, Picard C & Casanova JL.
Septicemia without sepsis: inherited disorders of nuclear factor-kappa B-mediated
inflammation. Clin. Infect. Dis. 2005, 41 Suppl 7: S436-439.
Yang K, Puel A, Zhang S, Eidenschenk C, Ku CL, Casrouge A, Picard C, von Bernuth H,
Senechal B, Plancoulaine S, Al-Hajjar S, Al-Ghonaium A, Marodi L, Davidson D, Speert D,
Roifman C, Garty BZ, Ozinsky A, Barrat FJ, Coffman RL, Miller RL, Li X, Lebon P,
Rodriguez-Gallego C, Chapel H, Geissmann F, Jouanguy E & Casanova JL. Human TLR-7-,
-8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and
23.
redundant for protective immunity to viruses. Immunity. 2005, 23: 465-478.
Feinberg J, Fieschi C, Doffinger R, Feinberg M, Leclerc T, Boisson-Dupuis S, Picard C,
24.
Bustamante J, Chapgier A, Filipe-Santos O, Ku CL, de Beaucoudrey L, Reichenbach J,
Antoni G, Balde R, Alcais A & Casanova JL. Bacillus Calmette Guerin triggers the
IL-12/IFN-gamma axis by an IRAK-4- and NEMO-dependent, non-cognate interaction
between monocytes, NK, and T lymphocytes. Eur. J. Immunol. 2004, 34: 3276-3284.
Puel A, Picard C, Ku CL, Smahi A & Casanova JL. Inherited disorders of
25.
NF-kappaB-mediated immunity in man. Curr. Opin. Immunol. 2004, 16: 34-41.
Picard C, Puel A, Bonnet M, Ku CL, Bustamante J, Yang K, Soudais C, Dupuis S, Feinberg J,
Fieschi C, Elbim C, Hitchcock R, Lammas D, Davies G, Al-Ghonaium A, Al-Rayes H,
Al-Jumaah S, Al-Hajjar S, Al-Mohsen IZ, Frayha HH, Rucker R, Hawn TR, Aderem A,
Tufenkeji H, Haraguchi S, Day NK, Good RA, Gougerot-Pocidalo MA, Ozinsky A &
26.
Casanova JL. Pyogenic bacterial infections in humans with IRAK-4 deficiency. Science. 2003,
299: 2076-2079.
Picard C, Puel A, Bustamante J, Ku CL & Casanova JL. Primary immunodeficiencies
27.
associated with pneumococcal disease. Curr. Opin. Allergy Clin. Immunol. 2003, 3: 451-459.
Impact Factor and Journal Ranking is according to the JCR of the year of publication or of 2012.

CONFERENCE
9,8,7,6,5,4,3,1,2
1.
2.
3.
The 16th Biennial Meeting of the European Society for Immunodeficiencies; Prague, Czech
Republic. 2014/10/29-11/02. "Anti-Interferon-Gamma Autoantibodies in Adults with
Disseminated Nontuberculous Mycobacterial Infections Are Associated with
HLA-DRB1*16:02 and DQB1*05:02", Poster. Supported by NHRI.
The 16th Biennial Meeting of the European Society for Immunodeficiencies; Prague, Czech
Republic. 2014/10/29-11/02. "Severe Enterovirus 71 Infection in Children with Toll-Like
Receptor 3 Deficiency", Poster Talk. Supported by CMRP. [Best Poster Award]
Joint Symposium Between Taiwan-Austria Research Commmunites: Host-Pathogen
Interaction: Regulation of Innate Immuntiy Signaling; Taipei Medical University, Taipei,
Taiwan. 2014/05/06-07. "Anti-Interferon-γ Autoantibodies in Adults with Disseminated
Nontuberculous Mycobacterial Infections: From clinical to mechanism. ", Oral. Supported by
Ku, C.L.
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4.
15th International Congress of Immunology; Milan, Italy. 2013/08/22-27. "Presence of
5.
6.
7.
8.
9.
Ku, C.L.
Anti-Interferon Gamma Autoantibodies in Mycobacterial Infected Patients Associated with
the HLA-DRB1*16:02 and DQB1*05:02", Poster. Supported by NHRI.
The Innate Immune Response in the Pathogenesis of Infectious Disease; Ouro preto, Brazil.
2013/05/09-15. "Presence of Anti-Interferon Gamma Autoantibodies in Mycobacterial
Infected Patients Associated with the HLA-DRB1*16:02 and DQB1*05:02", Poster.
Supported by Bill & Melinda Gates Foundation.
Taiwan-UK Conference on Life Sciences; Oxford, UK. 2012/09/01-02. "Anti-Cytokine
Autoantibodies (ACADs): A Crossroad of Autoimmune and Infectious Disease", Invited
speaker. Supported by
Human Immunity; Lisbon, Portugal. 2012/08/19-21. "Presence of Anti-Interferon Gamma
Autoantibodies in Mycobacterial Infected Patients Associated with the HLA-DRB1*16:02
and DQB1*05:02", Poster. Supported by NHRI.
8th International Congress on Autoimmunity; Granada, Spain. 2012/05/09-13. "Presence of
Anti-Interferon Gamma Autoantibodies in Mycobacterial Infected Patients Associated with
the HLA-DRB1*16:02 and DQB1*05:02", Oral Presentation. Supported by NSC.
CHSA Immunity & Infection; Suzhou, China. 2011/09/08-12. "Disseminated Nontuberculous
Mycobacterial Infections in Patients with Anti-Interferon-gamma Autoantibodies", Oral
presentation. Supported by NHRI.
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