Research


Cell and Molecular Biology

Dr. KM Yao

Dr Yao, Kwok Ming (丘國明)

Associate Professor, Department of Biochemistry

BSc, MPhil (Hong Kong); PhD (Brandeis U, Mass.)

Contact
Email: kmyao@hku.hk
Tel: (852) 3917 9275; 3917 6812 (lab)
Office: L3-69, Laboratory Block, 21 Sassoon Road, Hong Kong

Brief Biography:

Kwok-Ming Yao is currently Associate Professor in the Department of Biochemistry, The University of Hong Kong. He graduated from Brandeis University (Genetics, Molecular and Developmental Biology program) with a PhD degree in 1992.  After postdoctoral training at Dana Farber Cancer Institute and Harvard Medical School (1993-1994) and then Genetics Institute, Inc., Cambridge, MA (1994-1996), he joined the University of Hong Kong as Assistant Professor in 1997 and was promoted to Associate Professor in 2009. He has published more than 40 peer-reviewed articles including papers in Science, Molecular and Cellular Biology, Journal of Biological Chemistry, The EMBO Reports, Journal of Cell Science, Diabetes and Endocrinology.

Research Description:

FOXM1 and regulation of cancer and stem cell function
Dr. Yao cloned FOXM1 when he was a postdoctoral fellow at Genetics Institute, Inc. (GI). His lab first demonstrated that FOXM1 over-expression stimulates cyclin B1 expression and enhances progression through the G2/M phase of the cell cycle. FOXM1 was later shown by Dr. Yao’s lab to be regulated by MAPK signaling, strongly indicating a pivotal role played by FOXM1 in mediating the growth promoting effect of mitogens. Further, Dr. Yao and his collaborators discovered that FOXM1 regulates the transcription of the estrogen receptor α in breast cancer cells and is involved in the regulation of cervical cancer progression and the migration/invasion of ovarian cancer cells, and that FoxM1 counteracts oxidative stress-induced senescence and stimulates Bmi-1 expression in mouse embryonic fibroblasts. Recently, Dr. Yao’s lab presented evidence to support the hypothesis that the b isoform, which is frequently over-expressed in cancers, represents a more active form of FOXM1. Most recently, Dr. Yao has initiated collaboration with Prof Y Tan (Hunan U) to investigate the role of FOXM1 in the regulation of genome stability and pluripotency in human embryonic stem cells.

PDZ Domain-containing protein 2 (PDZD2) and regulation of pancreatic b-cell formation
Dr. Yao also cloned PDZD2 as a highly expressed gene in pancreatic beta cells when he was a postdoctoral fellow at GI. PDZD2, with a relative molecular mass of approximately 300 kDa, contains six different PDZ protein–protein interaction domains, which are thought to act as molecular scaffolds to facilitate the assembly of macromolecular complexes. Dr. Yao’s lab demonstrated that PDZD2 is proteolytically cleaved by caspase-3 to generate the secreted protein, sPDZD2. This is analogous to the processing of pro-IL-16 to generate the secreted cytokine, IL-16. Expression of sPDZD2 in pancreas and other tissues suggests an extracellular signaling function for sPDZD2. Dr. Yao and his collaborators showed that sPDZD2 exists at high levels in human fetal pancreas and in pancreatic progenitor cells derived from human fetus. Recent studies revealed that depletion of both the full-length and secreted forms of PDZD2 in rat insulin-secreting INS-1E cells led to dramatic attenuation of mRNA expression of Insulin1, Glut2 and MafA, whereas addition of recombinant sPDZD2 (at 10-10 M) stimulated the expression of these beta-cell genes and the activity of the insulin promoter. Interestingly, depletion of the full-length form (but not the secreted form) of PDZD2 in two gene-trap mutant mouse lines led to increased basal insulin secretion, revealing a novel role for PDZD2 in the regulation of basal insulin secretion probably via modulation of KATP channel activity

FOXM1 and signal transduction pathway
PDZD2 immunostaining
PDZD2 western blot

Recent RGC-funded Projects:

  • Secreted PDZ domain-containing protein 2 and regulation of Sonic hedgehog signaling during neural tube development
  • Investigating the role of FOXM1 in the maintenance of human embryonic stem cell pluripotency and genome stability

Postgraduate Research Projects Available:

  • Functional characterization of FOXM1 isoforms in cancer cells
  • Identifying the Planarian (S. mediterranea) homologs of FOXM1 and FOXO1 transcription factors
  • sPDZD2 and regulation of pancreatic beta cell functon

Selected Publications:

  1. Lam AK, Ngan AW, Leung MH, Kwok DC, Liu VW, Chan DW, Leung WY and Yao KM (2013) FOXM1b, which is present at elevated levels in cancer cells, has a greater transforming potential than FOXM1c. Front. Oncol. 3:11. doi: 10.3389/fonc.2013.00011.
  2. Cui J, Wang Z, Cheng Q, Lin R, Xin-Mei Z, Leung PS, Copeland NG, Jenkins NA, Yao KM and Huang JD (2011) Targeted inactivation of kinesin-1 in pancreatic β–cells in vivo leads to insulin secretory deficiency. Diabetes 60: 320-30.
  3. Tsang SW, Shao D, Cheah KSE, Okuse K, Leung PS and Yao KM (2010) Increased basal insulin secretion in Pdzd2-deficient mice. Mol. Cell Endocrinol. 315: 263-270.
  4. Leung KK, Suen PM, Lau TK, Ko WH, Yao KM and Leung PS (2009) PDZ-domain containing-2 (PDZD2) drives the maturity of human fetal pancreatic progenitor-derived islet-like cell clusters with functional responsiveness against membrane depolarization. Stem Cells Dev. 18:979-990.
  5. Li SK, Smith DK, Leung WY, Cheung AM, Lam EW, Dimri GP and Yao KM (2008) FoxM1c counteracts oxidative stress-induced senescence and stimulates Bmi-1 expression. J. Biol. Chem. 283: 16545-16553.
  6. Madureira PA, Varshochi R, Constantinidou D. Francis RE, Coombes RC, Yao KM and Lam EW (2006) The Forkhead box M1 protein regulates the transcription of the estrogen receptor alpha in breast cancer cells. J. Biol. Chem. 281: 25167-25176.
  7. Tam CW, Cheng AS, Ma RY, Yao KM and Shiu SY (2006) Inhibition of prostate cancer cell growth by human secreted PDZ domain-containing protein 2, a potential autocrine prostate tumor suppressor. Endocrinology 147(11):5023-5033.
  8. Ma RYM, Tong THK, Cheung AMS, Tsang ACC, Leung WY, and Yao KM (2005) Raf/MEK/MAPK signaling stimulates the nuclear translocation and transactivating activity of FOXM1c. J. Cell Sci. 118: 795-806.
  9. Yeung ML, Tam TSM, Tsang ACC and Yao KM (2003) Proteolytic cleavage of PDZD2 generates a secreted peptide containing two PDZ domains. EMBO Rep. 4: 412-418.
  10. Yao KM,  Sha M, Lu Z, and Wong GG (1997) Molecular analysis of a novel winged helix protein, WIN (later renamed FOXM1). Expression pattern, DNA binding property, and alternative splicing within the DNA binding domain. J. Biol. Chem. 272: 19827-19836.

Other Achievements:

  • Holders of three patents
  • Consultant to Genetics Institute, Cambridge, MA, USA from 1996 to 1998
  • Invited reviewer of FOXM1 network in NCI-Nature Pathway Interaction Database  and Springer Science on book chapter “Epigenetics of Aging"
  • Invited Reviewer of journals (FEBS Letters, Cancer Letters, Cancer Gene Therapy, Hepatology, Journal of Molecular Endocrinology, PLoS ONE, Molecular Cancer Research, Biochimica et Biophysica Acta -Molecular Cell Research, etc.)
  • Invited Reviewer for Grant agencies – National Science Foundation (USA) CAREER Program Review, Cancer Research UK Project Grant Application Review, Genesis Oncology Trust (New Zealand), Hong Kong Baptist University Research Committee
  • Supervision of Research Postgraduate Students: 18 PhD, 12 MPhil, 6 MMedSc

Full List of Publications, Achievements, and Grants: