Professor Chim, James Chor Sang 詹楚生
|2006||The University of Hong Kong||Ph.D.|
|1999||Royal College of Physicians and Surgeons of Glasgow||FRCP(Glasgow)|
|1995||Hong Kong Academy of Medicine||FHKAM|
|2011||Royal College of Pathologists of Australasia||FFSc (RCPA)|
|2007||Royal College of Pathologists||FRCPath (UK)|
|2004||American College of Physicians||FACP|
|2002||The University of Hong Kong||MD|
|2002||Royal College of Physicians||FRCP(London)|
|1999||Royal College of Physicians of Edinburgh||FRCP(Edinburgh)|
|1995||Hong Kong Academy of Medicine||FHKCP|
|1991||Royal College of Physicians||MRCP(UK)|
|1986||The Chinese University of Hong Kong||MB ChB|
Professor Chim focuses on understanding the role of DNA methylation of tumour suppressor protein-coding genes and non-coding RNAs in multiple myeloma and other haematological cancers. DNA methylation refers to the covalent addition of a methyl (-CH3) group to the carbon 5 position of a cytosine ring in a CpG dinucleotide. In carcinogenesis, dysregulation of DNA methylation attributes to global DNA hypomethylation, and locus-specific DNA hypermethylation. Particularly, tumour suppressor gene with a promoter-associated CpG island, clustered CpG dinucleotides, is usually hypermethylated, leading to the formation of a closed chromatin configuration, which precludes the access of transcription factors, and hence gene silencing.
Professor Chim was among the first pioneers to elucidate the role of gene hypermethylation by a cancer pathway-specific approach in myeloma. In particular, his research has demonstrated DNA methylation and hence silencing of SHP1 but not SOCS1 accounted for constitutive activation of JAK-STAT signalling in myeloma (Blood 2004). Moreover, DNA methylation-mediated silencing of soluble Wnt inhibitors resulted in constitutive activation of the canonical Wnt signalling in myeloma (Leukemia 2007). On the other hand, he has also showed DNA methylation of negative regulators of cell cycle progression was implicated in disease progression from monoclonal gammopathy of undermined significance (MGUS), the premalignant stage of myeloma, to symptomatic or progressive myeloma (Leukemia 2003). Furthermore, he has also found DNA methylation of DAPK1, an upstream activator of TP53 tumour suppressor, is an adverse prognostic factor for inferior survival, which has subsequently been confirmed in a uniformly-treated cohort of myeloma patients (J Clin Pathol. 2007; J Transl Med. 2010).
Recently, miRNA has emerged as a novel class of short single-stranded non-coding RNAs, which inhibit expression of target protein-coding genes through binding to their three prime untranslated region (3’-UTR). In carcinogenesis, oncogenic miRNAs targeting tumour suppressor genes are known as oncomiRs, whereas tumour suppressive miRNAs targeting oncogenes are known as tumour suppressor miRNAs.
Professor Chim was the first to establish several original observations for the role of DNA methylation in the regulation of tumour suppressor miRNAs in myeloma. His studies on miR-34 family miRNAs, direct targets of TP53 tumour suppressor, have illustrated DNA methylation of miR-34b/c was implicated in myeloma relapse/progression (Carcinogenesis 2010; Blood 2011). Moreover, he has identified CREB as a novel target of tumour suppressive miR-203 in myeloma and demonstrated methylation of miR-203 was implicated in myelomagenesis (Br J Haematol. 2011). Furthermore, he has also showed methylation of miR-129-2 was implicated in progression from MGUS to symptomatic myeloma (J Hematol Oncol. 2013). Hence, aberrant methylation of tumour suppressor miRNAs is implicated in the pathogenesis and disease progression of myeloma.
Currently, Professor Chim strives to identify bona fide tumour suppressor miRNAs silenced by DNA methylation in myeloma in a genome-wide scale, which integrates high-throughput miRNA microarray platforms, DNA methylation arrays, and data derived from high-resolution array-comparative genomic hybridization (aCGH), single-nucleotide polymorphism (SNP) arrays, and chromosomal regions with recurrent deletions or mutations [also known as cancer-associated genomic regions (CAGRs)]. Moreover, based on his expertise on gene methylation and survival, he is elucidating the potential of miRNA methylation as an independent prognostic factor impacting on response rate, event-free survival and overall survival in a uniformly-treated cohort of myeloma patients. Furthermore, since epigenetic drugs are coming-of-age, his research may contribute to the scientific basis of epigenetic therapy in myeloma.
|Awardees||Award Date||Honours / Awards / Prizes||Category|
|2009-12-01||National Scientific and Technological Advancement Award, Eipigenetic alterations in acute leukaemia: China, 國家科學技術進步獎 (二等獎), 白血病表觀遺傳學基礎及臨床應用研究||Research Achievement|
|1992-09-01||Croucher Foundation Fellowship: Croucher Foundation||Research Achievement|
|2012-02-01||Epigenetic Inactivation of the MIR34B/C in Multiple Myeloma/ Best Abstract: 3rd International Hematologic Malignancies Conference/ The Asia Pacific Hematology Society||Research Achievement|
|2005-09-25||Distinguished Poster Award, "Correlation between the single-site CpG mutation within the gene promoter and the expression silencing of XIAP -Associated Factor 1 (XAF1) in human colon cancer cell lines": Asian Pacific Digestive Week, Sept. 25-28, Seoul, Korea||Research Achievement|
|2007-12-01||Fellow of the Royal College of Pathologist (UK): The Royal College of Pathologist||Research Achievement|
|2013-12-01||Faculty Knowledge Exchange (KE) Award 2013: 'Multi-media Haematology Protocol: Haematology Protocol Book, iPad/iPhone App, Internet Website' (Group Award): The University of Hong Kong||Teaching Accomplishment|
|Term Period||Position||Professional Societies|
|2003-now||Council member||Federation of Medical Societies of Hong Kong|
|2002-now||Council member||Hong Kong Cancer Chemotherapy Society|
|2005-now||Director||Foundation of Federation of Medical Societies of Hong Kong|
|2007-2010||Consultant||Hematological Oncology Division, Quangzhou Anti-cancer Society|
|2010-2012||Founding President||Hong Kong Society of Myeloma|
|Jul 2008||Advisory Board Member||International Myeloma Working Group, IMWG|
|2007-2008||Council member||Hong Kong Society of Haematology|
|2008-now||Consultant||Physicians’ Information and Education Resources (PIER), American College of Physicians|
|2005-now||Scientific Officer||Hong Kong Society for the Study of Thalassemia|
|2003-2006||Chairman||Hong Kong Society of Haematology|
|2000-2003||Honorary Treasurer||Hong Kong Society of Haematology|
|1999-2000||Honorary Secretary||Hong Kong Society of Haematology|
|1998-1999||Scientific Officer||Hong Kong Society of Haematology|
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