|
Research Training and Experience:
From Research Fellow to the rank of Associate
Professor,
The
Scripps Research Institute
Ph.D., Medical Science, University
of Calgary
M.Sc., Clinical Chemistry, University
of Calgary
B.Sc., Biochemistry, University of British
Columbia |
|
| Teaching Responsibilities:
Director,
GMS
5905 / DEN 8290 RNA interference and microRNAs: from advances in cell biology
to therapeutic applications in the treatment of human diseases
-
(update
page for GMS 5905 / DEN 8290
students)
Director,
IDP Core Course
GMS
6006 Fundamentals of Immunology & Microbiology
-
(update
page for GMS 6006 students)
DEN 6128
Structure and Function of Body System II: Host Defenses, lecture on Autoimmunity
and Autoimmune Diseases |
|
Active Professional Service:
Vice Chair, Autoantibody Standardization
Committee of IUIS
Website: AutoAbSC.org
or AutoAb.org |
|
| Lab
News: |
GW bodies as
cytoplasmic foci important for RNAi:
UF
Health Science Center News in lay language by Lindy McCollum-Brounley
Write
up in The Scientist by Charles Q. Choi, 2005 |
Autoimmune response to components of
RNAi pathway:
A
new target for autoimmunity by Ger J.M. Pruijn,
2006 |
| GW
bodies: from RNA biology to clinical implications in autoimmunity.by
Rafael Herrera-Esparza et al., 2008 |
|
A 4 color fluorescence image by Shangli
Jesse Lian |
| Research Interests: |
| Our interests are autoantigens and autoantibodies
associated with systemic autoimmune diseases and cancer. Our two main directions
are 1) to identify and characterize specific target antigens of human autoantibodies
with the focus on understanding why autoantibodies are induced and continually
produced in different disease states and 2) to use human autoantibodies
as unique probes to investigate the molecular and cell biology of interesting
macromolecules and subcellular organelles which have become autoimmune
targets. The overall strategy is that by understanding the biology of autoantigens
in health and disease states, we may be able to fully appreciate the functional
and pathogenic potentials of autoantibodies. |
| Our laboratory is actively characterizing
the mRNA associated protein GW182 which is a macromolecule marker of a
novel cytoplasmic compartment known as GW bodies (GWBs). The most common
clinical diagnosis of patients with anti-GW182 antibodies was Sjögren's
syndrome, followed by neurological disease (motor and sensory neuropathy
and/or ataxia), and systemic lupus erythematosus. Several novel autoantigens
have been identified in GWBs and we focus on their roles in the regulation
of RNA interference. GWB
page link |
 |
| GW
body - 200nm dia., immunoEM image colorized |
|
| Pauley, K.M. and Chan, E.K.L. (2008)
MicroRNAs and their emerging roles in immunology. In: Noel R. Rose
(ed), The Year in Immunology, Annals of the New York Academy of Sciences,
in press. |
| Kakumanu, P., Yamagata, H., Sobel, E.S.,
Reeves, W.H., Chan, E.K.L., and Satoh, M. (2008) Patients with
pulmonary tuberculosis are frequently positive for anti-CCP antibodies
but they also react with unmodified arginine peptide. Arthritis Rheum,
58:1576-1581. PubMed
abstract. |
| Nozawa, K., Fritzler, M.J., Ikeda, K.,
Takasaki, Y., Satoh, M., and Chan, E.K.L. (2008) Differential anti-Golgi
complex autoantibody production in murine lactate dehydrogenase-elevating
virus infection. Immunopharmacology and Immunotoxiclogy 30:13-25.
PubMed
abstract. |
| Moser, J.J., Eystathioy, T., Chan, E.K.L.,
and Fritzler, M.J. (2007) Markers of mRNA stabilization, degradation
and RNAi within astrocytoma GW bodies. J. Neuroscience Research,
85:3619-3631. PubMed
abstract. |
| Bhanji, R.A., Eystathioy, T., Chan, E.K.L.,
Bloch, D.B., and Fritzler, M.J. (2007) Clinical and serological features
of patients with autoantibodies to GW/P Bodies. Clin. Immunol., 125:247-256.
PubMed
abstract. |
| Lian, S., Fritzler, M.J., Katz, J., Hamazaki,
T., Terada, N., Satoh, M., and Chan, E.K.L. (2007) Small interfering
RNA-mediated silencing induces target-dependent assembly of GW/P bodies.
Mol. Biol. Cell, 18:3375-87. PubMed
abstract. Expert
Reviews written by Herrera-Esparza et al, 2008 |
| Junttila,M.R., Puustinen, P., Niemelä,
M., Ahola, R., Nielsen, C., Kallunki, T., Ivaska, J., Arnold, H., Lu, S.,
Wang, X.J., Chan, E.K.L., Grenman, R., Kast, J., Sears, R., Kähäri,
V., and Westermarck, J. (2007) CIP2A inhibits PP2A in human malignancies.
Cell 130:51-62. PubMed
abstract. |
| Chan, E.K.L., Fritzler, M.J., Wiik, A.,
Andrade, L.E.C., Reeves, W.H., Tincani, A., Meroni, P.L., and the IUIS/WHO/AF/CDC
committee for the standardization of autoantibodies in rheumatic and related
diseases. (2007) AutoAbSC.Org – Autoantibody Standardization Committee
in 2006. Autoimmunity Reviews 6:577-580. PubMed
abstract. |
| Jakymiw, A., Pauley, K.M., Li, S., Lian,
S., Ikeda, K., Eystathioy, T., Satoh, M., Fritzler, M.J., and Chan, E.K.L.
(2007) The role of GW/P-bodies in RNA processing and silencing. J.
Cell Sci., 120:1317-23. A commissioned commentary. PubMed
abstract. |
| Yamasaki, Y., Narain, S., Yoshida, H.,
Hernandez, L., Barker, T., Hahn, P.C., Sobel, E.S., Segal, M.S., Richards,
H.B., Chan, E.K.L., Reeves, W.H., and Satoh, M. (2007) Autoantibodies
to RNA helicase A: A new serological marker of early lupus. Arthritis
Rheum. 56:596-604. PubMed
abstract. |
| Zhang, J.Y., Megliorino, R., Peng, X.X.,
Tan, E.M., Chen, Y., and Chan, E.K.L. (2007) Antibody detection using tumor-associated
antigen mini-array in immunodiagnosing human hepatocellular carcinoma.
J. Hepatol., 46:107-114. PubMed
abstract. |
| Kopp, K., Gasiorowski, J. Z., Chen, D.,
Gilmore, R., Norton, J.T., Wang, C., Leary, D.J., Chan, E.K.L., Dean, D.A.,
and Huang, S. (2007) Pol I transcription and pre-rRNA processing
are coordinated in a transcription dependent manner in mammalian cells.
Mol. Biol. Cell, 18:394-403. PubMed
abstract. |
| Ikeda, K., Satoh, M., Pauley, K.M., Fritzler,
M.J., Reeves, W.H., and Chan, E.K.L. (2006) Detection of the argonaute
protein Ago2 and microRNAs in the RNA induced silencing complex (RISC)
using a monoclonal antibody. J. Immunol. Methods, 317:38-44. PubMed
abstract. |
| Pauley, K.M., Eystathioy, T., Jakymiw,
A., Hamel J.C., Fritzler, M.J., and Chan, E.K.L. (2006) Formation
of GW bodies is a consequence of miRNA genesis. EMBO Reports. 7:904-910.
PubMed
abstract. |
Jakymiw, A., Ikeda, K., Fritzler, M.J.,
Reeves, W.H., Satoh, M., and Chan, E.K.L. (2006) Autoimmune targeting
of key components of RNA interference. Arthritis Res. Ther., 8:R87.
PubMed
abstract and link
to article. |
| Chan, E.K.L. (2006) Ninth international
workshop on autoantibodies and autoimmunity. Autoimmunity
Reviews Vol 5, issue 6. pdf
file (1.5MB) |
| Yamasaki, Y., Narain, S., Ikeda, K., Honkannen-Scott,
M., Hernandez, B.S., Barker, T., Richards, H.B., Chan, E.K.L., Reeves,
W.H., and Satoh, M. (2006) Nucleolar staining cannot be used
as a screening test for the scleroderma marker anti-RNA polymerase I/III
antibodies. Arthritis Rheum. 54:3051-6. PubMed
abstract. |
| Yamasaki, Y., Narain, S., Hernandez, L.,
Barker, T., Ikeda, K., Segal, M.S., Richards, H.B., Chan, E.K.L., Reeves,
W.H., and Satoh, M. (2006) Autoantibodies to the replication
protein A complex in SLE and other autoimmune diseases. Arthritis
Res. Ther. 8:R111. PubMed
abstract and link
to article. |
| Lian, S., Jakymiw, A., Eystathioy, T.,
Hamel, J.C., Fritzler, M.J., and Chan, E.K.L. (2006) GW bodies, microRNAs
and the cell cycle. Cell Cycle 5:242-5. PubMed
abstract pdf file (472kB) |
| Yamasaki, Y., Yamada, H., Nozaki, T.,
Akaogi, J., Nichols, C., Lyons, R., Loy, A.C., Chan, E.K.L., Reeves, W.H.,
and Satoh, M. (2006) Unusually high frequency of autoantibodies
to PL-7 associated with milder muscle disease in Japanese patients with
polymyositis/dermatomyositis. Arthritis Rheum. 54:2004-2009. PubMed
abstract pdf file (93kB) |
| Jakymiw, A., Lian, S., Eystathioy,
T., Li, S., Satoh, M., Hamel J.C., Fritzler, M.J., and Chan, E.K.L.
(2005) Disruption of GW bodies impairs mammalian RNA Interference.
Nature Cell Biology 7:1167-74. PubMed
abstract pdf file (2,087kB) |
| Clancy, R.M., Buyon, J.P.,
Ikeda, K., Nozawa, K., Argyle, D.A., Friedman, D.M., and Chan, E.K.L.
(2005) Relationship of maternal antibody responses to the 52kD SS-A/Ro
p200 peptide and the development of fetal conduction defects. Arthritis
Rheum. 52:3079-3086. PubMed
abstract pdf file (103kB) |
| Nozawa, K., Fritzler, M.J.,
and Chan, E.K.L. (2005) Unique and shared features of Golgi
complex autoantigens. Autoimmunity Reviews. 4:35-41. PubMed
abstract pdf file (176kB) |
| Himoto, T., Kuriyama, S.,
Zhang, J.Y., Chan, E.K.L., Nishioka, M., and Tan, E.M. (2005) Significance
of autoantibodies against insulin-like growth factor II mRNA-binding proteins
in patients with hepatocellular carcinoma. Int J Oncol. 26:311-7.
PubMed
abstract pdf file (1.4MB) |
| Megliorino, R., Shi, F.D.,
Peng, X.X., Wang, X., Chan, E.K.L., Tan, E.M., and Zhang, J.Y. (2005) Autoimmune
response to anti-apoptotic protein survivin and its association with antibodies
to p53 and c-myc in human malignancies. Cancer Detect. Prev. 29:241-8.
PubMed
abstract pdf file (215kB) |
Lu, Y., Ye, P., Chen, S-L.,
Tan, E.M., and Chan, E.K.L. (2005) Identification of kinectin
as a novel Behcet’s disease autoantigen. Arthritis Res. Ther. 7:R1133-1139.
PubMed
abstract and link
to article.  |
| Himoto, T., Kuriyama, S.,
Zhang, J.Y., Chan, E.K.L., Kimura, Y., Masaki, T., Uchida, N., Nishioka,
M., and Tan, E.M. (2005) Analyses of autoantibodies against tumor-associated
antigens in patients with hepatocellular carcinoma. Int J Oncol.
27:1079-1085. PubMed
abstract pdf file (1,780kB) |
| Shi, F.D., Zhang, J.Y., Liu,
D., Rearden, A., Elliot, M., Nachtsheim, D., Daniels, T., Casiano, C.A.,
Heeb, M.J., Chan, E.K.L., and Tan, E.M. (2005) Preferential
humoral immune response in prostate cancer to cellular proteins p90 and
p62 in a panel of tumor associated antigens. Prostate 63:252-258.
PubMed
abstract pdf file (117kB) |
Yang, Z., Jakymiw, A., Wood,
M.R., Eystathioy, T., Rubin, R.L., Fritzler, M.J., and Chan, E.K.L. (2004)
GW182 is critical for the stability of GW bodies expressed during the cell
cycle and cell proliferation. J. Cell Science 117:5567-78. PubMed
abstract pdf file (1.96MB)
GWBs
movies |
| Nozawa, K., Fritzler, M.J.,
von Mühlen , C.A. , and Chan, E.K.L. (2004) Giantin is the major Golgi
autoantigen in human anti-Golgi complex sera. Arthritis Res. Ther., 6:R95-R102.
PubMed
abstract pdf file (492kB) |
| Julkunen, H., Miettinen,
A., Walle, T.K., Chan, E.K.L., and Eronen, M. (2004) Autoimmune response
in mothers of children with congenital and postnatally diagnosed isolated
heart block: a population based study. J. Rheumatol. 31:183-189. PubMed
abstract |
| Zhang, J.Y., Casiano , C.A.
, Peng, X.X., Koziol, J.A., Chan, E.K.L., and Tan, E.M. (2003) Enhancement
of antibody detection in cancer using panel of recombinant tumor-associated
antigens. Cancer Epidemiology, Biomarkers, and Prevention 12:136-43. PubMed
abstract pdf file (454kB) |
| Eystathioy, T., Chan, E.K.L.,
Mahler, M., Luft, L.M., Fritzler, M.L., and Fritzler, M.J. (2003) A panel
of monoclonal antibodies to cytoplasmic GW bodies and the mRNA binding
protein GW182. Hybridoma & Hybridomics, 22:79-86. PubMed
abstract pdf file
(619kB) |
| Eystathioy, T., Jakymiw,
A., Chan, E.K.L., Séraphin, B., Cougot, N., and Fritzler, M.J. (2003)
The GW182 protein co-localizes with mRNA degradation associated proteins
hDcp1 and hLSm4 in cytoplasmic GW bodies. RNA 9:1171-1173. PubMed
abstract pdf file (120kB) |
| Fritzler, M.J., Wiik, A.,
Tan, E.M., Smolen, J.S., McDougal, J.S., Chan, E.K.L., Gordon, T.P., Hardin,
J.A., Kalden, J.R., Lahita, R.G., Maini, R.N., Reeves, W.H., Rothfield,
N.F., Takasaki, Y., Wilson, M., Byrd, M.G., Slivka, L., and Koziol, J.A.
(2003) A critical evaluation of enzyme immunoassay kits for detection of
antinuclear autoantibodies of defined specificities. III. Comparative performance
characteristics of academic and manufacturers' laboratories. J. Rheumatol.
30:2374-2381. PubMed
abstract pdf file (233kB) |
| Koziol, J.A., Zhang, J.Y.,
Casiano , C.A. , Peng, X.X., Shi, F.D., Feng, A.C., Chan, E.K.L., and Tan,
E.M. (2003) Recursive partitioning as an approach to selection of immune
markers for tumor diagnosis. Clinical Cancer Research, 9:5120-5126. PubMed
abstract pdf file (231kB) |
| Eystathioy, T., Chan, E.K.L.,
Takeuchi, K., Mahler, M., Luft, L.M., Zochodne, D.W., and Fritzler, M.J.
(2003) Clinical and serological associations of autoantibodies to GW bodies
and a novel cytoplasmic autoantigen GW182. J. Mol. Med., 81:811-818. PubMed
abstract pdf file (676kB) |
| Eystathioy, T., Peebles,
C.L., Hamel, J.C., Vaughan, J.H., and Chan, E.K.L. (2002) Autoantibody
to hLSm4 and the heptameric LSm complex in anti-Sm sera. Arthritis Rheum.
46:726-734. PubMed
abstract pdf file (519kB) |
| Eystathioy, T., Chan, E.K.L.,
Tenenbaum, S.A., Keene, J.D., Griffith, K., and Fritzler, M.J. (2002) A
phosphorylated cytoplasmic autoantigen, GW182, associates with a unique
population of human mRNAs within novel cytoplasmic speckles. Mol. Biol.
Cell 13: 1338-51. PubMed
abstract pdf file (1.58MB) |
| Nozawa, K., Casiano, C.A.,
Hamel, J.C., Molinari, C., Fritzler, M.J., and Chan, E.K.L. (2002) Fragmentation
of Golgi complex and Golgi autoantigens during apoptosis and necrosis.
Arthritis Res. 4:R3. PubMed
abstract pdf file (1.17MB) |
| Soo-Hoo, L., Zhang, J.Y.,
and Chan, E.K.L. (2002) Cloning and characterization of a novel 90kDa “companion”
autoantigen of p62 overexpressed in cancer. Oncogene 21:5006-5015. PubMed
abstract pdf file (783kB) |
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