Skip to content | Change text size

Professor Benjamin Li

Professor

PhD ( Imperial College, University of London, UK)

Telephone: +603 - 551 46083
Fax: +603 - 551 46364
E-mail: Benjamin.Li@artsci.monash.edu.my

Links
Area of Expertise
Research Interest
Selected Journals
Prospective Research Projects
Keynote Lecture/Seminar
Summary of Research
Publications

Area of Expertise:

DNA repair and DNA-methylation

Research Interest:
Mechanisms of chemical-induced cancer
Selected Journal Papers:

Badal V, Chuang LS, Tan EH, Badal S, Villa LL, Wheeler CM, Bernard HU, Li BFL (2003) CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimens: genomic hypomethylation correlates with carcinogenic progression. J Virol 77: 6227-6234 Teo AKC, Oh HK, Ali RB, Li BFL (2001)The modified human DNA repair enzyme O 6-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage. Mol Cell Biol 20: 7105-7114

Prospective Research Projects:

Honour year projects

  • DNA-methylation patterns of HPV16 as a model for carcinogen- induced genomic hypomethylation
  • DNA-methylation pattern of the ribosomal DNA as biomarker for aging and DNA-damage/response center
  • Mechanism of reactive oxygen formation (ROS) by estrogen in estrogen receptor (ERα) +ve and –ve breast cells
  • Mechanism of MGMT inhibitor 0 6-benzylguanine mediated growth-inhibition of p53-/- lung cells

MSc/PhD projects

  • The role of DNA-methyltransferase DNMT1 in micronuclei formation and genomic stability
  • The role of DNA-repair enzyme MGMT in regulation of the p53/MDM2/MDMX complex
Keynote Lecture/Seminar :
  1. Department of Physiology NUS, 19 May 2001. “Regulation of the Estrogen Receptor by DNA repair enzyme MGMT Upon Alkylation DNA Damage”
  2. A-Star IMCB Singapore, 29 July 2005. “Chemical Carcinogenesis”
  3. HKUST Cancer Conference, 11 Jan 2001. “The repaired human DNA repair enzyme MGMT as a repressor for the Estrogen Receptor“
  4. HKCU Cancer Conference, 2 March 2007. “Towards a mechanistic role of Oxidative damage (Estrogen), Estrogen Receptor, MGMT and BRCA1 in breast cancer”

Summary of Research :


The Integrity of our Genetic Material

Our genetic material, the DNA, is the blueprint of our well-being as well as the cause of our death (i.e. Cancer). Genetic analysis of human cancer has revealed that abnormalities in a number of genes are involved in tumor transition. Based on the possible functions of these gene products and the properties of tumor cells, it has been suggested that there could be a hierarchy in their malfunctions in relationship to the different stages of carcinogenesis. The genes at the high hierarchy can be considered as a biological "Gate" whereas the lowers are “Caretakers”. In a model for colon cancer, it has been suggested that the APC gene is a "Gate" whereas p53 and the Mismatch repair proteins are "Caretakers". However, it is yet unknown how the "Gate" and "Caretaker" genes are related since these genes are necessary but not sufficient as an individual to cause tumor transformation.

To maintain its integrity, the genetic material encodes macro-molecules (proteins) to check its health (DNA Repair Enzymes) and activity (DNA-Methyltransferases). Indeed, abnormalities in either DNA Repair or DNA-Methylation are frequently observed in cancer cells. Dr Li’s research focuses on understanding the functions of these proteins and their applications as biomarkers and targets for chemotherapy in cancer.

Publications :

1.

Badal S, Badal V, Calleja-Macias IE, Kalantari M, Chuang LS, Li BF, Bernard HU (2004) The human papillomavirus-18 genome is efficiently targeted by cellular DNA methylation. Virology 324: 483-492

2.

Badal V, Chuang LS, Tan EH, Badal S, Villa LL, Wheeler CM, Bernard HU, Li BFL (2003) CpG methylation of human papillomavirus type 16 DNA in cervical cancer cell lines and in clinical specimens: genomic hypomethylation correlates with carcinogenic progression. J Virol 77: 6227-34

3.

Chuang LSH, Tan EH, Oh HK, Li BFL (2002) Selective depletion of human DNA-methyltransferase DNMT1 proteins by sulfonate-derived methylating agents. Cancer Res Adv Brief 62: 1592-1597

4.

Teo AKC, Oh HK, Ali RB, Li BFL (2001) The modified human DNA repair enzyme O 6-methylguanine-DNA methyltransferase is a negative regulator of estrogen receptor-mediated transcription upon alkylation DNA damage. Mol Cell Biol 20: 7105-7114

5.

Bin Ali R, Teo AKC, Oh HK, Chuang LSH, Ayi TC, Li BFL (1998) Implication of Localization of Human DNA repair enzyme 0 6-Methylguanine-DNA Methyltransferase at active transcription sites in Transcription-Repair Coupling of the mutagenic 0 6-methylguanine lesion. Mol Cell Biol 8: 1660-1669

6.

Chuang LSH, Ian HI, Koh TW, Ng HH, Xu G, Li BFL (1997) Human DNA-(Cytosine-5) Methyltransferase - PCNA complex as a target for p21 WAF1.Science 277: 1996-2000

7.

Wang L, Zhu D, Zhang C, Mao X, Wang G, Mitra S, Li BFL, Wang X and Wu M (1997) Mutations of O 6-methylguanine-DNA methyltransferase gene in esophageal cancer tissues from Northern China. Int J Cancer 71:719-723

8.

Oh HK, Teo AKC, R. Bin Ali, A. Lim, Ayi TC, Yarosh DB, Li BFL (1996)Conformational change in human DNA repair enzyme O 6‑methylguanine‑DNA methyltransferase upon alkylation of its active site by DNA damage-related SN1 and direct-acting SN2 Alkylating Agents: breaking a “salt-link”? Biochemistry 35:12259-12266

9.

Lin Y, Shi CY, Li BFL, Soo BH, Mohammed-Ali S, Wee A, Oon CJ, Mack PO, Chan SH (1996) Tumour suppressor p53 and Rb genes in human hepatocellular carcinoma. Ann Acad Med Singapore 25:22-30

10.

Lim A, Li BFL (1996) The nuclear-targeting and nuclear-retention properties of a human DNA repair protein 0 6-Methylguanine-DNA Methyltransferase are both required for its nuclear localization: the possible implications. EMBO J 15: 4050-4060

11.

Chuang LSH, Ng HH, Chia JN, Li BFL (1996) Characterization of independent DNA and multiple Zn-binding domains at the N- terminus of human DNA-(Cytosine-5) Methyltransferase: modulating the property of a DNA-binding domain by contiguous Zn-binding motifs. J Mol Biol 257: 935-948

12.

Belanich M, Randall T, Pastor MA, Kibitel JT, Alas LG, Dolan ME, Schold SC Jr, Gander M, Lejeune FJ, Li BFL, White AB, Wasserman P, Citron ML, Yarosh DB (1996) Intracellular Localization and intercellular heterogeneity of the human DNA repair protein O 6-methylguanine-DNA methyltransferase.. Cancer Chemother Pharmacol 37:547-555

13.

Belanich M, Pastor M, Randall T, Guerra D, Kibitel J, Alas L, Li BFL, Citron M, Wasserman P, White A, Eyre H, Jaeckle K, Schulman S, Rector D, Prados M, Coons S, Shapiro W, Yarosh D (1996) Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res 56:783-788

14.

Shi CY, Phang TW, Wee A, Ngoi SS, Lin Y, Li BFL, Ong CN, Lee HP (1995) Mutations of the tumour suppressor gene p53 in colorectal and hepatocellular carcinomas. Ann Acad Med Singapore 24:204-210

15.

Chi CY, Phang TW, Lin Y, Wee A, Li BFL, Lee HP, Ong CN (1995) Codon 249 mutation of the p53 gene is a rare event in hepatocellular carcinomas from ethic Chinese in Singapore. Br J Cancer 72: 146-149

16.

Zaidi NH , Allay E, Ayi TC, Li BFL, Dumenco LL, Sy MS, Gerson SL (1995) The immature thymocyte is protected from N-methylnitrosourea induced lymphoma by the human MGMT-CD2 transgene. Carcinogenesis 16: 1047-1053

17.

Citron M, White A, Decker R, Wasserman P, Li BFL, Randall T, Guerra D, Belanich M, Yarosh D (1995) O 6-methylguanine-DNA methyltransferase in human brain tumors detected by activity assay and monoclonal antibodies. Oncology Res 7:49-55

18.

Shi CH, Phang TW, Ngoi SS, Wee A, Li BFL, Lin Y, Lee HP, Ong CN (1994) Characterisation of p53 gene mutations in Colorectal Carcinomas from an Asian population. Anticancer Res 14: 2871-2816

19.

Fones-Tan A, Chan SH, Tsao SY, Gan LH, Tan WH, Li BFL, Khong PW, Gan YY (1994) Enzyme-linked immunosorbent assay (ELISA) for IgA and IgG antibodies of Epstein-Barr Virus ribonucleotide reductase in patients with Nasopharyngeal Carcinoma. Int J Cancer 59: 1-4

20.

Gan YY, Fones-Tan, Chan SH, Tsao SY, Li BFL, Tan WH (1994) Molecular cloning and expression of Epstein-Barr Virus antigens in the lambda gtll expression vector: antibodies towards proteins from the BORF2 and BKRF4 reading frames in Nasopharyngeal Carcinoma Patients. Intervirology 37: 233-235

21.

Belanich M, Ayi TC, Li BFL, Kitibel J, Rob DG, Randall T, White A, Citron M and Yarosh DB (1994) Analysis of 0 6-methylguanine-DNA methyltransferase inindividual human cells by quantitative immunofiuorescence microscope. Oncology Res 6: 129-137

22.

Ayi TC, Oh HK, Lee TKY, Li BFL (1994) A method for the simultaneous identification of human active and active-site alkylated DNA repair enzyme, 0 6-methylguanine-DNA methyltransferase, and its application for monitoring human exposure to alkylating carcinogens. Cancer Res 54: 3726 - 3731

23.

Liem LK, Lim A, Li BFL (1994) Specificities of human, rat and E. coli 0 6-methylguanine-DNA methyltransferase in the repair of 0 6-­methyl and 0 6-ethylguanine in DNA. Nucleic Acids Res 22: 1613-1619

24.

Wong CW, Li BFL (1994) A method of locating 0 6-methylguanine residues in DNA. Nucleic Acids Res 22: 882-883

25.

Liem LK, Wong CW, Lim A, Li BFL (1993) Factors influencing the repair of the mutagenic lesion 0 6-methylguanine in DNA by human 0 6­methylguanine-DNA methyltransferase. J Mol Biol 231: 950-959

26.

Ayi TC, Loh KC, Bin Ali R, Li BFL (1992) Intracellular localization of human DNA repair enzyme 0 6-methylguanine-DNA methyltransferase by antibodies and its importance. Cancer Res 52: 6423-6430

27.

Wong CW, Tan NW, Li BFL (1992) Structure related properties of the mutagenic lesion 0 6-methylguanine in DNA. J Mol Biol 228: 1137-1146

28.

Tan NW, Li BFL (1990) The interaction of oligonucleotide containing 0 6-methylguanine with human DNA-(cytosine-5-) ­methyltransferase. Biochemistry 29: 9234-9240

29.

Kalnik MW, Norman DG, Li BFL, Swann PF, Patel DJ (1990) Conformational transitions in thymidine bulge-containing deoxytridecanucleotide duplexes. Role of flanking sequence and temperature in modulating the equilibrium between looped out and stacked thymidine bulge states. J Biol Chem 265: 636-647

30.

Webster GD, Sanderson MR, Skelly JV, Neidle S, Swann PF, Li BFL, Tickle IJ (1990) Crystal structure and sequence-dependent conformation of the A.G mispaired oligonucleotide d(CGCAAGCTGGCG). Proc Natl Acad Sci USA 87: 6693-6697

31.

Graves RJ, Li BFL, Swann PF (1989) Repair of O 6-methylguanine, O 6-ethylguanine, O 6-isopropylguanine and O 4-methylthymine in synthetic oligodeoxynucleotides by Escherichia coli ada gene O 6-alkylguanine-DNA-alkyltransferase. Carcinogenesis 10:661-666

32.

Kalnik MW, Li BFL, Swann PF and Patel DJ (1989) O 6-ethylguanine carcinogenic lesions in DNA: an NMR study of O 6etG.T pairing in dodecanucleotide duplexes. Biochemistry 28:6170-6181

33.

Kalnik MW, Li BFL, Swann PF, Patel DJ (1989) O 6-ethylguanine carcinogenic lesions in DNA: an NMR study of O 6etG.C pairing in dodecanucleotide duplexes. Biochemistry 28: 6182-6192

34.

Li BFL, Holdup D, Morton CAJ, Sinnott ML (1989) The catalytic consequences of experimental evolution. Transition-state structure during catalysis by the evolved B-galactosidases of E. Coli (ebg enzymes) changed by a single mutational event. Biochem J 260:109-114

35.

Li BFL, Swann PF (1989) Synthesis and characterisation of oligonucleotides containing 0 6-methyl, 0 6-ethyl and 0 6-isopropylguanine. Biochemistry 28: 5779-5786

36.

Kalnik MW, Kouchakdjian M, Li BFL, Swann PF, Patel DJ (1988) Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of A.C and A.O 4meT pairing in dodecanucleotide duplexes. Biochemistry 27: 100-108

37.

Kalnik MW, Kouchakdjian M, Li BFL, Swann PF, Patel DJ (1988) Base pair mismatches and carcinogen-modified bases in DNA: an NMR study of G.T and G.O 4meT pairing in dodecanucleotide duplexes. Biochemistry 27: 108-115

38.

Kouchakdjian M, Li BFL, Swann PF, Patel DJ (1988) Pyrimidine.pyrimidine base-pair mismatches in DNA. A nuclear magnetic resonance study of T.T pairing at neutral pH and C.C pairing at acidic pH in dodecanucleotide duplexes. J Mol Biol 202:139-155

39.

Li BFL, Swann PF, Kalnik MW, Kouchakdjian M, Patel DJ (1988) NMR spectroscopy in Drug research: Carcinogen and DNA interaction. Alfred Benzon Symp 26: 30-45

40.

Li BFL, Swann PF, Kalnik MW, Patel DJ (1987) Synthesis and structural studies by nuclear magnetic resonance of dodecadeoxynucleotides containing O 6-methylguanine, O 6-ethylguanine and O 4-methylthymine. Int Agent Res Cancer IARC Sci Publ 84:44-48

41.

Graves RJ, Li BFL, Swann PF (1987) Repair of synthetic oligonucleotides containing O 6-methylguanine, O 6-ethylguanine and O 4-methylthymine, by O 6-alkylguanine-DNA alkyltransferase. Int Agent Res Cancer IARC Sci Publ 84:41-43

42.

Li BFL, Reese CB, Swann PF (1987) Synthesis and characterization of oligodeoxynucleotides containing 0 4-methylthymine. Biochemistry 26:1086-1093

43.

Teo I, Sedgwick B, Demple B, Li BFL, Lindahl T (1984) Induction of resistance to alkylating agents in E. coli: the ada + gene product serves both as a regulatory protein and as an enzyme for repair of mutagenic damage. EMBO J 3:2151-2157

44.

Li BFL, Osborne S, Sinnott ML, Yates DW (1983) Catalytic consequences of experimental evolution Part 2, Rate-limiting degalactosylation in the hydrolysis of Aryl-D-galacto pyranosides by experimental ebg. J Chem Soc Perkin Trans II, p 365

45.

Challis BC , Li BFL (1982) Formation of N-nitrosamines and N-nitramines by photolysis. Int Agent Res Cancer IARC Sci Publ 41:31-40