(1) Proteomics

Proteomics, a powerful emerging technology for new biomarkers and drugs discovery, presents promising breakthroughs in diseases prevention and treatment. We apply proteomic techniques for search of disease biomarkers in the following: renal disease, liver cancer, necrotizing enterocolitis, diet-induced obesity as well as Chinese medicinal mushroom and toxic marine algae.

       

Representative publications:

Ngai Heidi Hoi-Yee, Sit Wai Hung, Jiang Ping-Ping, Thongboonkerd Visith, Wan Jennifer Man Fan (2007). Differential Proteomics Study Reveals Urinary Preprohaptoglobin and Haptoglobin as Potentially Novel Biomarkers for Passive Heymann Nephritis. (In press, J Proteome Research).
Ngai Heidi Hoi-Yee, Sit Wai Hung, Jiang Ping-Ping, Thongboonkerd Visith, Wan Jennifer Man Fan (2007). Differential Proteomics Study Reveals Urinary Preprohaptoglobin and Haptoglobin as Potentially Novel Biomarkers for Passive Heymann Nephritis. (In press, J Proteome Research).
Cheuk-Lun Lee, Ping-Ping Jiang, Wai-Hung Sit and Jennifer Man-Fan Wan (2007)  Proteome of Human T lymphocytes with Treatment of Cyclosporine and Polysaccharopeptide: Analysis of Significant Proteins that Manipulate T cells Proliferation and Immunosuppression. (In press,  International Immunopharmacology.
Ngai Heidi Hoi-Yee, Sit Wai Hung, Jiang Ping-Ping, Xu Ruo-Jun, Wan Jennifer Man Fan, Thongboonkerd Visith. Serial Changes in Urinary Proteome profile of membranous nephropathy: implications for Pathophysiology and biomarker discovery. J Proteome Research 2006, 5, 3038-3047.
Leo Lai Chan, Wai-Hung Sit, Paul Kwan-Sing Lam, Dennis Paul Hsientang Hsieh, Ivor John Hodgkiss, Jennifer Man-Fan Wan, Alvin Yam-Tat Ho, Nicola Man-chi Choi and David Dudgeon. (2007) Identification and characterization of “Biomarker of toxicity” from the proteome of Paralytic Shellfish toxin (PST)-producing dinoflagellates Alexandrium tamarense (Dinophycae). Proteomics. (In press).
Chan L.L., Hodgkiss I.J., Lam P.K.S., Wan J.M.F., Chou N.H., Lum J.H.K., Lo M.G.Y., Mak A.S.C., Sit W.H. and Lo S.C.L. (2005) Use of 2-DE to differentiate morphospecies of Alexandrium minutum, a paralytic shellfish poisoning toxins (PST)-producing dinoflagellate of Harmful Algal Blooms. Proteomics 5: 1580-1593.
Chan L.L., Hodgkiss I.J., Wan J.M.F., Lum J.H.K., Mak A.S.C., Sit W.H. and Lo S.C.L. (2004) Proteomic study of a model causative agent of harmful algal blooms, Prorocentrum triestinum II: The use of differentially expressed protein profiles under different growth phases and growth conditions for bloom prediction. Proteomics 4: 3214-3226.

 

(2) Chinese Medicine

Chinese herbal medicines have been used to treat cancer, infection, inflammation, diabetes, heart disease etc for more than three thousand years in China. Until now, their efficacy has not been systematically reviewed. Our team has been working on Chinese medicine since 1997 with research focus on certain bioactive metabolites extract from some Chinese medicinal mushroom. Genomic, proteomic and flow cytometry techniques are used to investigate their anticancer, anti-inflammatory and immune function. We were the first to publish the detailed anticancer mechanisms of polysaccharide peptide (PSP), an extract of the Chinese Medicinal mushroom Yun zhi (Coriolus versicolor, spp).  Flow cytometry and cDNA arrays technology were used to identify the cell cycle kinetics, cell death and apoptotic pathways in which PSP exhibits its treatment effect on human leukemia. PSP is currently used in China as adjuvant therapy. Our data show that PSP does not exert cytotoxic effect on normal healthy human cells thus further supports its potential development as chemotherapeutic drug in the west.

Representative publications:

2.1 Chinese medicine and Cancer
Lee L, Yang XT and Wan JMF. (2006) The culture duration affects the immunomodulatory and anticancer effect of polysaccharopeptide derived from Coriolus versicolor. Enzyme and microbial technology  38: 14-21.
Lau CS, Fanya Zeng, Chung-Chau Hon, Wai-Hung Sit, Ken Yan-Ching Chow, Raymond Kin-Hi Hui, Ivy Ka-Man Law, Victor Wai-Lap Ng, Frederick Chi-Ching Leung and Jennifer Man-Fan Wan. (2005) Molecular characterization of Coriolus versicolor PSP-induced apoptosis in human promyelotic leukemic HL-60 cells using cDNA microarray. International Journal of Oncology 26: 0-00.
Hui K.P.Y., Sit W.H. and Wan J.M.F. (2005) Induction of S phase cells arrest and caspase activation by polysaccharide peptide (PSP) isolated from coriolus versicolor enhanced the cell-cycle-dependent activity and apoptotic cell death of Doxorubicin and Etoposide but not Cytarabine in HL-60 cells. Oncology Reports. 14(1): 145-165.
Xiaotong Yang, Wai-Hung Sit, Daniel Kwong-On Chan, Jennifer Man-Fan Wan. (2005) The Cell Death Process of the Anticancer Agent Polysaccharide-peptide (PSP) in Human Promyelocytic Leukemic HL-60 Cells. Oncology Reports 13(6): 1201-1221.
Cheng Le Le, Yang Xiao Tong, Mi Ke,  Wan Jennifer Man Fan, Yang Qing Yao. Colorimetric detection of total Triterpene contents in Fruiting Bodies and spores of Ganoderma Lucidum (Leyss.Ex Fr) Karst (2005). Mycosystema Vol: 24 p. 317-320.
Yang Xiatong-Tong, Wan JMF, Ke MI and Feng HQ. (2003) The quantification of (1,3)-b-Glucan in edible and medicinal mushroom polysaccharides by using limulus G test. Mycosystema 22 (2): 296-302.
Pang ZJ, Chen Y, Zhou M and Wan J. (1999) The effect of polysaccharide krestin on nitric oxide production in mouse peritoneal macrophages. Medical Science Research 27(5): 299-302.
Wan JMF, Yang M and Sit WH. (1997) Mechanisms of Yun Zhi control of tumor cell proliferation. Chinese J. Integrated and Western Medicine. 3: 73-77.
Wan, JMF and WH. Sit. Mechanisms of Yun Zhi Control of Tumor Cell Proliferation. p244-246 Adanced Research in PSP. International Symposium on Chinese Medicine, The University of Hong Kong. The Hong Kong Assication for Health Care Ltd. Publisher, 1999.
Heidi H.Y. Ngai, W. H. Sit and Jennifer M.F. Wan. (2005) The nephroprotective effects of the Herbal Medicine Preparation, WH30+, on the chemical-induced acute and chronic renal failure in rats. The American Journal of Chinese Medicine 33(3): 491-500.
2.2 Chinese medicine, Infection and Immune Function
Cheuk-Lun Lee, Ping-Ping Jiang, Wai-Hung Sit and Jennifer Man-Fan Wan. (2006). The culture duration affects the immunomodulatory and anticancer effect of polysaccharopeptide derived from Coriolus versicolor. (In press,  International Immunopharmacology 38: 14-21.
Jennifer Man-Fan Wan, Wai-Hung Sit, Cheuk-Lun Lee, Kelvin Hoi-Man Fu and Daniel Kwong-On Chan, Protection of Lethal Toxicity of Endotoxin by Salvia miltiorrhiza BUNGE is via Reduction in Tumor Necrosis Factor Alpha Release and Liver Injury (2006). International Immunopharmacolog 6: 750-758.
Kumar D. Siava Sundara Kumar, Lau Chak Sing, SS, Wan Jennifer MF, Yang Dan, Hyde Kevin D. Immunomodulatory compounds from Pestalotiopsis leucothes, an endophytic ungus from Tripterygium wilfordii (2005). Life Sciences 78:147-156.
Lee J. Wan JMF. Immunostimulatory Efficiency of YunZhi and Quercetin, p151-152.  International Symposium on Chinese Medicine, The University of Hong Kong. Advanced Research in PSP. The Hong Kong Association for Health Care Ltd. Publisher, 1999.
2.3 Chinese Medicine and Arthrosclerosis
Zhou M, Chen Y, Liu S, Ding Z, Pang Z, and Wan J. (1998). Oxidative and malondialdehyde modification of low-density lipoprotein; a comparative study of binding and degradation by macrophages and endothelial cells. British Journal of Biochemical Science, 55: 192-198.
Pang ZJ, Zhou M, Chen Y, Wan J. (1998). L929 cell-conditioned medium reduces the impairment in plasma membrane fluidity of U937 and J774 cell lines treated with tert-butyl hydroperoxide. Medical Science Research 26(4): 241-243.
Zhou M, Chen Y, Wan J. (1997). The polysaccharide krestin prevents lipoperoxidative injury to experimentally atherosclerotic rabbits. Medical Science Research 25: 137-140.
Chen Y, Zhou M, Leu N, Liu SX, Pang Z, Wan J. (1997). The polysaccharide krestin prevents plaque formation in experimentally atherosclerotic rabbits. Medical Science Research 25(5): 297-300.
Shang X L, Zhou M, Wan J. (1997). Apoptosis in mouse peritoneal macrophages induced by oxidized low-density lipoprotein and prevention by the polysaccharide kreskin. Medical Science Research 25(6): 429-437.
Zhou M, Chen Y, Pang Z, Wan J. (1997). Preparation and characterization of two monoclonal antibodies against oxidatively modified low-density lipoprotein (O-LDL) and detection of O-LDL in serum in patients with coronary heart disease. Medical Science Research 25(7): 445-449.
Shang XL, Chen Y, Zhou M and Wan J. (1997). Protective effect of the polysaccaride krestin on inhibition of lipopolysaccharides-induced nitric oxide production in macrophages caused by oxidized low-density lipoprotein. Medical Science Research 25(8): 507-509.
Chen Y, Zhou M, Wan J. (1997). Oxidative and malondialdehde modification of low-density liporotein: a comparative study. British Journal of Biomedical Science 54: 159-165.
Liu SX, Zhou M, Chen Y, Wen WY, and Wan J. (1996).Injury to mitochondria of mouse peritoneal macrophages caused by oxidised low-density lipoprotein, and protection afforded by polysaccharide krestin. Medical Science Research 24(10): 715-717.
Pang ZJ, Zhou M, Chen Y and Wan J. (1998). A Protein-bound Polysaccharide Synergistic with Lipopolysaccharide Induces Nitric Oxide Release and Antioxidant Enzyme Activities in Mouse Peritoneal Macrophages. American Journal of Chinese Medicine 26(2): 133-141.
Zhou M, Chen Y, Liu S, Ding Z, Pang Z, and Wan J. (1998). The effect of tert-butyl hydroperoxide on peritoneal macrophages and the protective effect of protein-bound polysaccharide administered intraperitoneally and orally. American Journal of Chinese Medicine 26(3-4): 301-310.

 

 

(3) Nutrition Research

Nutrition is closely linked to health and disease. At the genetic level (nutrigenomics), certain nutrients can upset genes-balance leading to diseases such as cancer, obesity and diabetes etc.  Significant nutrition research contributions are in the following areas: (i) Specific nutrients for hospital nutrition, (ii) oxidative stress and dietary antioxidant  (ii) dietary lipids and cancer, (iii) dietary lipids and immune function;  (iii) shock and burn;  (iv) nutrition and cytokines etc.

 

Representative publications:

  3.1. Nutrition and Cancer
  Chiu LCM, Ooi V, Wan J MF. (2001) Eicosapentaenoic acid modulates cyclin expression and arrests cell cycle progression I human leukemic K-562 cells. International Journal of Oncology 19: 845-849.
  Chiu L, Ooi VE and Wan JMF (2000) Induction of apoptosis by dietary polyundsaturated fatty acids in human leukemic cells is not associated with DNA fragmentation. International Journal of Oncology 17: 789-796.
  Chiu LCM and Wan JMF. (1999) Induction of apoptosis in HL-60 cells by eicosapentaenoic acid (EPA) is assoicated with downregulation of bcl-2 expression. Cancer Letters 145: 17-27.
  Istfan NW, Wan J, Chen ZY. (1995) Fish Oil and cell proliferation kinetics in a mammary carcinoma tumor model. Advances in Experimental Medicine & Biology 375: 149-56.
  Istfan N.W. Wan J.M. Bistrian B.R. and Chen, Z.Y. (1994) DNA replication time account for tumor growth variation induced by dietary fat in a breast carcinoma model. Cancer Letters 86(2): 177-86.
  Istfan NW. Wan JM, Bistrian BR. (1993) Nutrition and tumor promotion: In vivo methods for measurement of cellular proliferation and protein metabolism. Journal of Parenter Enteral Nutrition 16(6 Suppl): S76-S82.
  Wan JMF, Istfan NW, Chu, CC, Blackburn GL, Bistrian BR. (1991) Comparative effects of w-3 and w-6 polyunsaturated fatty acids on protein metabolism in rats bearing the mammary adenocarcinoma. Metabolism 40(6): 577-584.
 
3.2.  Nutrition, Infection and Immune Function
Wan JMF, Haw MP, Blackburn GL. (1989) Overview: Nutrition, immune function and inflammation: an overview. Proceedings of the Nutrition Society 48:315-335.
Wan JMF, Teo TC, Babayan VK, Blackburn GL. (1988) Invited Comment: Lipids and the development of immune dysfunction. Journal of Parenter Enteral Nutrition 12(6 Suppl): 43S-52S.
Wan JM, Grimble RF. (1987) Effect of dietary linoleate content on the metabolic response of rats to Escherichia coli endotoxin. Clinical Science 72:383-385.
Lee J and Wan JMF. (2000) Vitamin E supplementation improves cell-mediated immunity and oxidative stress of Asian Men and Women. Journal of Nutrition   130(12): 2923-27.
Chung-Yung Jetty Lee and Jennifer Man-Fan Wan. (2002) Immunoregulatory and Antioxidnat performance of a-tocopherol and selenium on human lymphocytes. Biological Trace Element Research 86(2): 123-135.
Wan JMF, Grimble R. (1998) Diurnal Factors Influence the Metabolic Response to Endotoxins. Nutrition Research 18: 265-272.

 

4.  Others  (Flow cytometry, cancer, shock, burn and lipid)

  Fogt F, Wan JM, O’Hara C, Bistrain BR, Blackburn GL, Istfan NW. (1991) Flow Cytometric measurement of cell kinetics in rat walker-256 carcinoma following in vivo and in vitro pulse labelling with bromodeoxyuridine. Cytometry 12:33-41.
  Wan JM, Fogt F, Bistrian BR and Istfan NW. (1993) Evaluation of the tumoricidal effect of tumor necrosis factor in relationship to tumor protein dynamics and cell kinetics in Walker-256 carcinosarcoma bearing rat. American Journal of Physiology-Cell Physiology 265: 365-374.
  Wan JM, Ye SH, Bistrian BR, and Isftan NW. (1994) The Effect of Interleukin-2 on Walker-256 tumor cell-cycle kinetics: -measured by flow cytometry. Journal of Leukocyte Biology 55(2): 241-247.
  Wan, J. M., Istfan N.W., Ye, S-L and Bistrian B.R. (1995) Insulin-like growth factor- 1 is not mitogenic for the Walker-256 Carcinosarcoma. Life Sciences 56(10): 747-756.
  Bagley JS, Wan J, Georgieff M, Forse RA, Blackburn GL. (1991) Cellular nutrition in support of early multiple organ failure. Chest 100:182S-188S.
  Teo TC, Selleck KM, Wan JM, Pomposelli JJ, Babayan VK, Blackburn GL, Bistrian BR. (1991) Long term feeding with structured lipid composed of MCT and fish oil ameliorates endotoxic shock in guinea pigs. Metabolism 40(11): 1152-1159.
  Pscheide EM, Wan JM, Blackburn GL, Bistrian BR, Istfan NW. (1992) Influence of w-3 fatty acids on splanchic blood flow and lactate metabolism in an endotoxemic rat model. Metabolism 41: 698-705.
  Selleck, K, Wan J.M., Gollaher C. Babayan V, Bistrian B. (1994) Energy expenditure in gastrostomy-fed burned rats receiving variable amounts of dietary fat. American Journal of Clinical Nutrition 60: 216-222.
 

Research Links and Current Collaborators:

1. Professor Per Sanglid, Department of Human Nutrition, Royal Veterinary and Agricultural University, Denmark.
2. Professor M Wang, Chengdu University of Traditional Chinese Medicine, Chengdu.
3. Professor ST Fan, Department of Surgery, The University of Hong Kong.
4. Professor CM, Che, Department of Chemistry, The University of Hong Kong.
5. Dr. LL Chan, Department of Ecology and Biodiversity, The University of Hong Kong.
6. Dr. Y. Sadovy, Department of Ecology and Biodiversity, The University of Hong Kong.
7. Professor B Bistrain, Cancer Research Institute, Harvard Medical School, USA. Departments of Medicine and Chemistry, The University of Hong Kong.
8. Dr. Yang Q Y. Department of Microbiology, Shanghai Teachers University, Shanghai.

International/Special Recognition:

1. Invited Plenary Lecture Speaker, The International Symposium on Bioinformatics and ChineseMedicine, organized by the Chengdu TCM University, Chengdu, China in 2004; Topic – Anti-inflammatory effect of Denshen”.
2. Invited Plenary Lecture Speaker, The 10th World Congress on Advances in Oncology and the 8th International Symposium on Molecular Medicine, Crete, Greece, 2005; Topic - The anticancer mechanisms of Yun Zhi polysaccharide peptides.
3. Invited Symposium lecture Speaker and Chairperson: During the 2nd, 4th, 6th and 10th Annual General Scientific Meeting of the Hong Kong Society of Flow Cytometry, Hong Kong in 1998, 2000, 2002, 2005; Topic areas: flow cytometry technology, Chinese medicine and cancer.
4. Invited Symposium Lecture Speaker and Chairperson: International Symposium on Chinese Medicine, Hong Kong in 1996, 1999; organized by The University of Hong Kong and The Hong Kong Association for Health Care.
5. Invited Symposium Lecture Speaker: The Hong Kong Society of Immunology 2005, HK.

Organizing Conferences:

1. Organizing committee member and co-chairperson on ” First International symposium in Chinese Medicine” jointly organized by the University of Hong Kong, and Hong Kong Association for Health Care Ltd. HK in 1996.
2. Organizing committee member and co-chairperson on ” International Conference on Polysaccharide peptide Research” organized by the Hong Kong Association for Health Care Ltd. HK in 1996.
3. Organizing committee member on “Hong Kong – the Centre for Chinese Medicine Development?”, organized by the Hong Kong Society of Traditional Medicine and Natural Products (1999).