Academic Staff > W.Y.P. Ching

Wilson Y. P. Ching ( 程翼鵬 )
Associate Professor
B.Sc., Ph.D. (U.K.)

Department of Anatomy
L1-43, Laboratory Block
Faculty of Medicine Building
21 Sassoon Road, Hong Kong

Anatomy Office: (852) 2819-9434 (voice)
Anatomy Office: (852) 2817-0857 (fax)

E-mail: ypching@hku.hk

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Background

Education / Training

  • B.Sc., Imperial College, University of London, UK

  • Ph.D., Dundee University, UK

  • Research Associate, Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong

  • Postdoctoral fellow, Institute of Molecular Biology, The University of Hong Kong, Hong Kong

  • Research Assistant Professor, Department of Pathology and Biochemistry, The University of Hong Kong, Hong Kong
  • Assistant Professor, Department of Anatomy, The University of Hong Kong, Hong Kong

 Other Affiliations

  • Member, Centre for Cancer Research, The University of Hong Kong

  • Honorary Principal Investigator, State Key Laboratory of Brain and Cognitive Sciences

  • Principal Investigator, State Key Laboratory for Liver Research

  • Honorary Assistant Professor, Department of Pathology, The University of Hong Kong, Hong Kong

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Research

Research Interests

  • Neuronal cell differentiation and migration

  • Rho GTPases signaling in cancer metastasis

  • Roles of centrosome in oncogenesis

 Research Description

Neuronal Cdc2-like kinase (Nclk)
Neuronal cdc2-like kinase (Nclk) has been shown to play an important role in neuronal differentiation, neuro-cytoskeleton dynamics, and neurite extension. Aberrant of Nclk activity has been implicated in a number of neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Nclk consists of a catalytic subunit, called cyclin dependent protein kinase 5 (Cdk5), and a 25 kDa regulatory subunit derived proteolytically from a 35 kDa neuronal-specific protein, called neuronal Cdk5 activator. Although Cdk5 protein exists ubiquitously, Nclk activity can only be found in brain because of the restricted expression of Cdk5 activator. This suggests that the activator is the crucial modulator for the Nclk activity. Thus our current researches focus on the identification of proteins that can interact with Cdk5 activators and can modulate the Cdk5 activity.

p21-activated protein kinase (Pak)
The small Rho GTPases family (including RhoA, Cdc42 and Rac1), which belongs to Ras small GTPase superfamily, is involved in a number of cellular processes including gene regulation, cell migration and cell division. Emerging evidences has shown that Rho GTPases also play a vital role in the regulation of neurite outgrowth and cell migration. One of the downstream effectors of Cdc42 and Rac1 is called p21-activated protein kinase (Pak), which contains a highly conserved N-terminal Cdc42/Rac1 binding domain and a C-terminal kinase domain. Six members of Pak kinase family have been identified and they are subdivided into 2 groups. Pak5, which belongs to the group II Pak family, is found to be highly expressed in brain and stimulates neurite outgrowth by downregulation of RhoA. Using the yeast-2 hybrid screening, we have identified several potential cellular partners of Pak5 and would like to further characterize the functional outcome of their interaction. Recently, we also found that group I Pak family member, Pak1, is overexpressed in liver cancer, which is one of the most common cancers worldwide and in Hong Kong. Thus, our researches also focus on the molecular mechanism by which Pak1 induces hepatocarcinogenesis. 

Centrosome and cancer
Emerging evidence suggests that supernumerary centrosomes drive chromosomal instability and is linked to oncogenesis. Several viral oncoproteins, such as human papillomavirus (HPV) type 16 E6 and E7 and hepatitis B virus X protein (HBx), have been shown to transform cells by promoting centrosome abnormalities and formation of multipolar spindles. Thus it appears that induction of centrosome amplification may be a common strategy for viral-mediated oncogenesis. We have recently characterized a novel cellular centrosomal protein, which we named TAX1BP2 and have shown to play an important role in centrosome duplication. Thus we would like to understand further the molecular signaling of TAX1BP2 and how centrosome overduplication contributes to the development of cancer.

Research Grants

  • RGC GRF (2005-09) “Roles and regulation of group II p21-activated protein kinases:-Implications in cancer metastasis”

  • RGC GRF (2006-10) “Roles of p21-activated protein kinase (Pak) 1 in the pathogenesis of liver cancer"

  • RGC GRF (2008-11) “Functional characterization of a putative tumour suppressor, AMP-activated protein kinase, in liver cancer"

  • RGC/NFSC Joint Research Scheme (2009-12) “The roles of CDK5 activator binding protein, LZAP, in the pathogenesis of neurodegenerative disease"

  • RGC GRF (2010-  ) “Functional characterisation of a novel centrosomal protein, TAX1BP2, in liver cancer development"
  • RFCID Full Grant (2010-  ) “Hepatitis B virus promotes hepatocarcinogenesis by activation of Pak1"
  • RFCID Full Grant (2012-  ) “HBx oncoprotein induces chromosome instability in hepatocarcinogenesis via dysregulation of centrosome duplication regulatory protein, TAX1BP2"

Awards and Honors

  • National Natural Science Foundation of China (NSFC) Young Scholar Award (2006-2007)

  • Faculty Outstanding Research Output Award, The University of Hong Kong (2007)

Editorship

  • PLoS One, Academic Editor

  • World Journal of Hepatology, Academic Editor

  • Anatomy and Physiology, Academic Editor

  • World Journal of Clinical Oncology, Academic Editor

Lab Personnel

  • Dr. Benny Lai (PDF)

  • Dr. Edith Tse (PDF)

  • Dr. Sheila Lee (PDF)

  • Miss Tiffany Tang (PhD)

  • Mr. Kay Kwan (M.Phil)

  • Mr. Eddie Kung (M.Phil)

  • Ms. Yuan Zhou (Technician)

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Selected Publications

  1. Lai WL, Hung WH, *Ching YP.  The tumor suppressor, TAX1BP2, is a novel substrate of ATM kinase.  Oncogene advance online publication, 18 November 2013; doi-10.1038/onc.2013.481.
     

  2. Wong LL, Lam IPY, Wong TYN, Lai WL, Liu HF, Yeung LL, *Ching YP. IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-B activation.  PLoS One (2013) Jul 19;8(7):e68843. doi: 10.1371/journal.pone.0068843
     

  3. Chan CP, Siu YT, Kok KH, *Ching YP, *Tang HMV, *Jin DY. Group I p21-activated kinases facilitate Tax-mediated transcriptional activation of the human T-cell leukemia virus type 1 long terminal repeats. Retrovirology (2013) Apr 26;10:47. doi: 10.1186/1742-4690-10-47
     

  4. Lai WL, Hung WY, Wong LL, Zhou Y, Leong VY, Lee JMF, Ng IOL, Jin DY, *Ching YP. The centrosomal protein Tax1 binding protein 2 is a novel tumour suppressor in hepatocellular carcinoma regulated by cyclin-dependent kinase 2. Hepatology (2012) 56(5): 1770-1781.
     

  5. Lee CW, Wong LL, Tse EY, Liu HF, Leong VY, Lee JM, Hardie DG, Ng IOL, *Ching YP. AMPK promotes p53 acetylation via phosphorylation and inactivation of SIRT1 in liver cancer cells. Cancer Research (2012) 72(17): 4394-4404.
     

  6. Mak GW, Chan ML, Leong VY, Lee JM, Yau TO, Ng IOL, *Ching YP. Overexpression of a novel activator of PAK4, the CDK5 kinase-associated protein CDK5RAP3, promotes hepatocellular carcinoma metastasis. Cancer Research (2011) 71(8): 2949-2958.
     

  7. *Ching YP, Leong VYL, Lee MF, Xu HT, Jin DY, *Ng IOL. Pak1 is overexpressed in hepatocellular carcinoma and enhances cancer metastasis involving JNK activation and paxillin phosphorylation. Cancer Research (2007) 67:3601-3608.
     

  8. Ching YP, Chan SF, Jeang KT, Jin DY. Retroviral oncoprotein Tax targets coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication. Nature Cell Biology (2006) 8: 717-724.
     

  9. *Ching YP, Leong VYL, Wong CM, *Kung HF. Identification of an autoinhibitory domain of p21-activated protein kinase 5. J Biol Chem (2003) 278(36): 33621-33624.
     

  10. Ching YP, Wong CM, Chan SF, Leung TH, Ng DC, Jin DY, Ng IOL. Deleted in liver cancer (DLC) 2 encodes a RhoGAP protein with growth suppressor function and is underexpressed in hepatocellular carcinoma. J Biol Chem (2003) 278(12): 10824-10830.
     

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