If you don’t like our faces, listen to our fortnightly podcast E-Junkies where we lepak one corner with famous people, Your daily good stuff - AsiaOne stories delivered straight to your inbox, AsiaOne Online Pte Ltd. Company Registration No. Among these 4 members, JAK3 signaling is specifically related to T-cell development and proliferation (8) with loss-of-function mutations resulting in severe combined immunodeficiency characterized by the lack of T and NK cells (9). The JAK3A572V and JAK3A573V mutations were located at exon 12, in the Janus homology domain 2 (JH2) that negatively regulates the Janus homology domain 1 (JH1) kinase activity (Fig. Poon, K. Tay, C.C.Y. A research-intensive university with an entrepreneurial dimension, NUS is ranked consistently as one of the world's top universities. See the complete profile on LinkedIn and discover Gan’s connections and jobs at similar companies. The coding exons of JAK3 were fully sequenced in these 3 cell lines, and we confirmed that only NK-S1 harbored a homozygous JAK3A572V mutation. 2A) and constitutive phosphorylation of both JAK3 and STAT5 (Fig. The men's 1000 metres competition at the 2010 Asian Games in Guangzhou was held on 18 November 2010 at the Zengcheng Dragon Boat Lake. This latter difference was not statistically significant (Supplementary Table S3). In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Koo, S.Y. Ng, V. Rajasegaran, S. Rozen, B.T. Lim, Writing, review, and/or revision of the manuscript: G.C. The single EBER-negative case was a cutaneous deposit taken from a patient with EBER+ nasal NKTCLs (Supplementary Table S3). All results are expressed as mean ± SEM of 3 independent experiments. A total of 3 μg of genomic DNA extracted from each sample was used for exome sequencing. Koo, S.Y. 4C). In parallel, these cells were harvested, and protein extracts were subjected to Western blotting with antibodies against phosphorylated JAK3 (p-JAK3), phosphorylated STAT5 (p-STAT5), JAK3, STAT5, or β-actin as a normalization control. CP-690550, a novel pan-JAK inhibitor, has recently been shown to inhibit adult TCL/leukemia (ATLL) cells (22) and ATLL xenograft tumors and is currently in phase III trials for the treatment of rheumatoid arthritis (23). View Ang Choon Kiat Amos’ profile on LinkedIn, the world’s largest professional community. : 201815023K. The HRM curves were analyzed with the Bio-Rad Precision Melt Analysis Software. Gan Choon Beng is a practicing lawyer and is the Senior Director at Infinitus Law Corporation and head of its Corporate, Commercial and Technology Department.He graduated from the University of Singapore (now known as the National University of Singapore) in 1977 with an LLB (Hons.) Ng, V. Rajasegaran, H.L. As such, it is possible that the number of homozygous tumors reported is actually an underestimate and that this value should be regarded as a lower limit. Koo, K.-W. Yeoh, C.C.Y. Choon Kiat Gan नाम के लोगों की प्रोफ़ाइल देखें. Gan Chimeg. Gan Arion. Teh, S.T. Join Facebook to connect with Kiat Gan and others you may know. Ng, C.K. Our findings have important implications for the management of patients with NKTCLs. NK-S1, established from a previously described NKTCL xenograft (27), was cultured in Dulbecco’s Modified Eagle’s Medium (DMEM; Life Technologies) supplemented with 10% heat-inactivated FBS and 10% equine serum. We are glad to play a part in our nation's 48th birthday celebration. Gan Choon Beng has been a GBN Mentor since 2008 and has worked with many mentees in various areas of business. He is a practicing lawyer and is a Partner at Infinitus Law Corporation and Head of its Corporate, Commercial and Technology Department. Lim, Supplied pathologic diagnosis for case series: L. Tan. Mr Gan first joined ComfortDelGro Corporation Limited as Group Corporate Planning Officer in February 2006. JAK3 siRNA or control siRNA (Dharmacon) were transfected into NK-S1 cell line using RNAiMAX (Invitrogen) according to the manufacturer’s protocols. The report said Gan, 61, was taking responsibility for an “inappropriate relationship”. B, NK-S1 cell lysates were harvested for Western blotting, and the results showed that phosphorylation of JAK3 and STAT5 are IL-2–independent. They also indicated that targeting the JAK/STAT pathway in this disease is a potentially effective therapeutic approach that warrants further investigation. B, KHYG-1 cells were transiently transfected with wild-type JAK3 (JAK3 WT) or mutated JAK3 expression vectors (i.e., JAK3A572V). ISSN: 2159-8274, Sign In to Email Alerts with your Email Address. He currently oversees The GBN Mentoring Program together with Seow Kiat Wang.. See more people named Choonkiat Gan. By continuing to use Gov.sg, you accept our use of cookies. Welcome to Singapore's directory of Specialist Doctors and Surgeons in private practice. Choon Kiat Chen Solutions Director , China Mobile International Choon Kiat has more than 25 years in the Telco/ICT industry since attaining his degree in Computing Science(1994) and MBA(2000). Yap, K.A. This study was funded by the National Medical Research Council of Singapore (NMRC/PPG/NCC/2011) as well as a grant from HSBC Trustee (Singapore) Limited as trustees of the Major John Long Trust Fund and the Chew Woon Poh Trust Fund. Note: Supplementary data for this article are available at Cancer Discovery Online (http://cancerdiscovery.aacrjournals.org/). The JAK3A572V and JAK3A573V mutations found in our samples were located at the JH2 pseudokinase domain that is known to have an autoinhibitory effect on the JH1 kinase domain. Currently, Choon Kiat Tan occupies the position of Group Financial Controller at SUTL Enterprise Ltd. Mr. Tan is also Member of Institute of Singapore Chartered Accountants. Consistent with the high frequency of JAK3 mutations (35%) in NKTCLs, use of CP-690550 in the JAK3-mutant NKTCL cell line showed inhibition in the phosphorylation of STAT5 along with reduced cell viability. Natural killer/T-cell lymphoma (NKTCL) is particularly prevalent in Asian countries and some parts of Latin America. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. Thus, it is conceivable that the JAK3 mutation may play an important role in the pathogenesis of NKTCLs. For HRM analysis, SsoFast EvaGreen Supermix (Bio-Rad, catalog number 172-5200) was used in the amplification of the sample amplicons using the JAK3 HRM primers at a final concentration of 600 nmol/L on a Bio-Rad CFX96 Real-Time PCR detection system in replicates. Lee, L.C. The next step uses a GATK Unified Genotyper that does the consensus calling to identify SNVs. The JAK3, JAK1, JAK2, and TYK2 mutation status in these samples was confirmed by Sanger sequencing of all coding exons. 4B). For Sanger sequencing, PCR was carried out with Platinum Taq Polymerase (Life Technologies, catalog number 10966-083) and cycled at 95°C for 10 minutes; 39 cycles of 95°C for 30 seconds; 60°C for 30 seconds, 72°C for 1 minute, and a final extension of 72°C for 10 minutes. He is also on the board of 11 other companies. Gan Ja. Ng, V. Rajasegaran, H.L. To date, transforming ability of the activating mutations of JAK3 (such as P132T, L156P, R172Q, E183G, Q501H, M511I, A572V, A573V, R657Q, and V722I) has been previously validated in Ba/F3 cells (8, 12, 19, 20). For FFPE samples, genomic DNA was extracted from one or two 10-μm slices from each sample by removal of paraffin followed by proteinase K digestion according to standard procedures. B, cell viability was analyzed by MTS assay after the cells were treated with their respective treatment for 72 hours. The relative p-JAK3, p-STAT5, JAK3, and STAT5 levels in these cells were detected by Western blotting (top), and proliferation assays using these cells were conducted for 48 hours with or without IL-2 (bottom). The JAK family of tyrosine kinases comprises 4 members: JAK1, JAK2, JAK3, and TYK2. Reciprocally, KHYG-1 cells transiently overexpressing a mutated JAK3 (JAK3A572V) cDNA showed IL-2–independent proliferation and autophosphorylation of JAK3 and STAT5 (Fig. *, P < 0.05 compared with vehicle control (vehicle). This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Tan, L. Tan, S.C. Chong, K. Tay, M. Tao, R. Quek, S. Loong, K.-W. Yeoh, S.P. ©2012 AACR. Yuen Kin Pheng is Professional at Tasek Corp. Bhd. 3A). The resulting products were run on an ABI 3730 DNA analyzer. Gan Choon Kiat, deputy director of the LTA's corporate transformation office, was quoted by Channel NewsAsia as saying that more themed trains will be rolled out in future. However, this phenomenon was not observed in the K562 cells in which STAT5 phosphorylation is dependent on BCR/ABL1 (8) and not JAK3 (Fig. Enter multiple addresses on separate lines or separate them with commas. eISSN: 2159-8290 We conducted whole-exome sequencing and identified Janus kinase 3 ( JAK3 ) somatic–activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Cells were seeded at 2 × 104 cells/100 μL/well in 96-well plates and treated with or without CP-690550 (Selleck Chemical, S5001) at various concentrations before being subjected to MTS assay (Promega). JAK-mutant (NK-S1) cells showed IL-2–independent growth (Fig. ): G.C. It accounts for up to half of all mature TCL cases in Asia (1). Among the patients with JAK3 mutations, there were 17 heterozygous JAK3A572V, 2 homozygous JAK3A572V, 2 heterozygous JAK3A573V, 1 homozygous JAK3A573V, and 1 heterozygous with both JAK3A572V and JAK3A573V mutations. This is the first time that the Land Transport Authority (LTA) has introduced a festive-themed train. As expected, both the NK-S1 and KHYG-1 cells showed a reduction of phosphorylated STAT5 (Fig. Subsequently, he was also appointed the Chief Executive Officer and Director of ComfortDelGro Bus Pte Ltd. To decline cookies at any time, you may adjust your browser settings. Choon kiat menyenaraikan 6 pekerjaan pada profil mereka. To decline cookies at any time, you may adjust your browser settings. These are some of the notable cases which SPD officers handled in 2011: In PP v Abdul Razak Bin Hamid and PP v Tan Chye Guan Martin, the accused persons were both heinous child molesters, dubbed the “Letterbox Molester” and “Heartbeat Molester” respectively.They engaged in ruses to con children into physical contact and committed the offences over 20 years and 11 years respectively. Interestingly, several somatic heterozygous Janus kinase (JAK) mutations were found in 2 separate samples. Others With a Similar Name. FFPE tissue blocks from 61 patients with NKTCLs were procured for mutation analysis. Facebook gives people the power to share and makes the world more open and connected. Gan Teng. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Were considered to be harboring a mutation proliferation and autophosphorylation of JAK3 and STAT5 ( Fig:... Half of all coding exons blocks from 61 patients with NKTCLs JAK3A572V-mutant cell! In Asia ( 1 ) mutation causes constitutive JAK3 and JAK3A572V expression vectors ( i.e., reporting or organizing,... 1 ) latter difference was not statistically significant ( Supplementary Table S3 ) for proliferation. Study is dedicated to Dr. Han Mo Koo in summary, our studies identified, for the management patients. Mentees in various areas of business blood samples from 4 consented patients NKTCLs! 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