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STAFF

Dr LAM Lai Kwan, Queenie | qlam@pathology.hku.hk
Research Assistant Professor
BSc McMaster, MPhil McMaster, PhD HKU

Research Interest

1. Role of leptin in humoral immune response
Accumulating evidence demonstrates that leptin acts as a proinflammatory cytokine in modulating the immune response. Leptin and leptin receptor deficient mice (ob/ob and db/db) exhibit impaired host defences, while humans with congenital deficiencies of leptin or leptin receptor show low T cell counts and increased incidence of infections. Our group was the first to report how leptin signaling promotes murine dendritic cell development but it remains largely unclear how leptin regulates the humoral response, the highlight of adaptive immune system. Impaired humoral response has been reported in immunized ob/ob and db/db mice and the expression of leptin receptor on B cells indicates a potentially direct effect of leptin on B cell function. Therefore, our group currently focuses on a series of studies to investigate the role leptin plays in the differentiation of B cells into antibody-secreting plasma cells. The anticipated findings will enrich our knowledge on the regulatory mechanisms of humoral immunity.

2. Role of leptin in B cell-derived malignancies
It has long been appreciated that an association between the development of cancer and inflammation exists. Obese individuals have high level of circulating leptin and are associated with increased risk of cancer, while common polymorphisms in the leptin gene or its receptor are linked to the pathogenesis of various hematological malignancies including non-Hodgkin’s lymphoma and multiple myeloma. Leptin is a potent proinflammatory cytokine which has been recently shown promote the growth of a variety of cancer cells. While most B cell lymphomas are associated with increased expressions of c-myc, Bcl-2 and a variety of cell cycle related genes, elevated level of plasmacytic transcription factors such as Blimp-1 and XBP-1 is characteristic of malignant plasma cells. Nevertheless, current understanding of external factors that lead to the observed aberrant gene expressions in B cell malignancies is far from complete. Therefore, we currently focus on dissecting how leptin signaling regulates critical factors that are involved in B cell tumorigenesis in light of discovery of therapeutic alternatives from a new angle.

Awards and Honors

Best Abstract Award, Annual Scientific Meeting, The Hong Kong Society for Immunology, Hong Kong (2009)

Best Abstract Award, Annual Scientific Meeting, The Hong Kong Society for Immunology, Hong Kong (2008)

Hong Kong Young Scientist Award, Hong Kong Institution of Science, Hong Kong (2007)
FOCIS Travel Award, The Federation of Clinical Immunology Societies (FOCIS) annual meeting, USA (2007)

RCAI Training and Internship Award, RIKEN Research Center for Allergy and Immunology (RCAI), Japan (2007)

Best Oral Presentation Award, The 11th Research Postgraduate Symposium, Li Ka Shing Faculty of Medicine, HKU, Hong Kong (2006)

Recent Publication Lists

Queenie Lai Kwan Lam, King-Hung Ko, Bo-Jian Zheng and Liwei Lu (2008). Local BAFF gene silencing suppresses Th17 cell generation and ameliorates autoimmune arthritis. *Proceedings of the National Academy of Sciences USA105(39):14993-14998. *Featured as “Research Highlights” in Nature Clinical Practice Rheumatology 5(2):62

Queenie Lai Kwan Lam, Bo-Jian Zheng, Dong-Yan Jin, Xuetao Cao and Liwei Lu (2007). Leptin induces CD40 expression through the activation of Akt in murine dendritic cells. The Journal of Biological Chemistry 38: 27587-27597

Queenie Lai Kwan Lam, Shuxun Liu, Xuetao Cao and Liwei Lu (2006). Involvement of leptin signalling in the survival and maturation of bone marrow-derived dendritic cells. *European Journal of Immunology 36: 3118-3130 (*Highlight article with commentary)

Queenie Lai Kwan Lam, Cherry Kam Chun Lo, King-Hung Ko, Dennis G. Osmond, Gillian E. Wu, Robert Rottapel and Liwei Lu (2007) Impaired VDJ recombination and increased apoptosis among precursor B cells in bone marrow of c-Abl deficient mice. International Immunology 19:267-276

Queenie Lai Kwan Lam and Lu L (2007). Role of leptin in immunity. Cellular & Molecular Immunology 4(1): 1-13.

Cherry Kam Chun Lo*, Queenie Lai Kwan Lam*, Min Yang, King-Hung Ko, Lingyun Sun, Rui Ma, Shengjun Wang, Huaxi Xu, Sidney Tam, Bo-Jiang Zheng and Liwei Lu (2009). Leptin signaling protects NK cells from apoptosis during development in mouse bone marrow. Cellular & Molecular Immunology 6(5):353-60. (*Equal contribution)

King-Hung Ko*, Queenie Lai Kwan Lam* , Min Zhang, Corinne Kung Yen Wong, Michelle Kahmeyer-Gabbe, Wai Hung Tsang, Cherry Kam Chun Lo , King-Hung Ko, Sze Lan Tsang , Li Chong Chan and Mai Har Sham and Liwei Lu (2007). Hoxb3 deficiency impairs B lymphopoiesis in mouse bone marrow. Experimental Hematology 35:465-475 (*Equal contribution)

Cherry Kam Chun Lo, Queenie Lai Kwan Lam, Lingyun Sun, Shengjun Wang, King-Hung Ko, Huaxi Xu, Chang-You Wu, Bo-Jian Zheng and Liwei Lu (2008). NK cell degeneration exacerbates experimental arthritis via enhanced IL-17 production. Arthritis and Rheumatism 58:2700-2711.

Noriko Iikuni, Queenie Lai Kwan Lam, Liwei Lu, Giuseppe Matarese and Antonio La Cava (2008). Leptin and inflammation. Current Immunology Reviews 4:70-79.

Min Zhang, King-Hung Ko, Queenie Lai Kwan Lam, Cherry Kam Chun Lo, Gopesh Srivastava, Bojian Zheng, Yu-Lung Lau and Liwei Lu(2005). Expression and function of TNF family member B cell activating factor in the development of autoimmune arthritis. International Immunology 17(8):1081-1092.

Mei-Xiang Yang, Xun Qu, Bei-Hua Kong, Queenie Lai Kwan Lam, Qian-Qian Shao, Bi- Ping Deng, King-Hung Ko and Liwei Lu (2006). Membrane type 1-matrix metalloproteinase is involved in the migration of human monocyte-derived dendritic cells. Immunology and Cell Biology 84: 557-562.

Xun Qu, Mei-Xiang Yang, Bei-Hua Kong, Lan Qi, Queenie Lai Kwan Lam, Shi Yan, Peng Li, Min Zhang, Liwei Lu (2005). Hypoxia inhibits the migratory capacity of human monocyte-derived dendritic cells. Immunology and Cell Biology 83:668-673

Min Zhang, King-Hung Ko, Queenie Lai Kwan Lam, Cherry Kam Chun Lo, Daniel Jia Lin Xu, Lijun Shen, Bojian Zheng, Gopesh Srivastava and Liwei Lu (2004). Novel function of TNF cytokines in regulating bone marrow B cell survival. Cellular and Molecular Immunology 1(6):447-453

Cascalho M., Martin D.A., Wong J., Queenie Lai Kwan Lam, Wabl M. and Wu G.E. (1999). A mouse with a monoclonal primary immunoglobulin repertoire not further diversified by V-gene replacement. Developmental Immunology 7(1):43-50

Larijani M., Yu C.C., Golub R., Queenie Lai Kwan Lam and Wu G.E. (1999). The role of components of recombination signal sequences in immunoglobulin gene segment usage: a V81x model. Nucleic Acids Research 27(11): 2304-9