1998-2003: Postdoctoral Fellow, Microbiology. University of California, Los Angeles
1992-1998: PhD; Immunology, University of Toronto
1988-1992: Master of Philosophy, Biochemistry. University of Hong Kong
1985-1988: Bachelor of Science, Biochemistry. University of Hong Kong
Department of Immunology
College of Medicine
Faculty of Health Science
University of Manitoba
Room 417, Apotex Centre
750 McDermot Avenue
Winnipeg, Manitoba, Canada R3E 0T5
Office Telephone: (204) 480-1301
Fax: (204) 789-3921
Improper regulation of immune system accounts for a large number of immune disorders. Innate immunity is the host'ss first line of defense, and is critically involved in determining the magnitude and nature of subsequent T cell and antibody mediated immune responses. The ability to regulate these processes , DC is capable of directing diverse functional development of T and B cells. It therefore holds great promises in therapeutic applications for immune disorders, and vaccine developments. However, the diverse functional plasticity of DC highlights the importance of thorough understanding of the critical regulatory elements involved in DC development and defining DC functions.
My laboratory established a lentiviral-based system to genetically modulate expression levels of a protein of interest in primary DC. (J. Immunol. Methods, 2009, 344:87-97). This novel platform will allow us to (i) examine factors involved in the differentiation of bone marrow-derived DC (or human monocyte-derived DC); (ii) examine functional signiﬁcance of the quantitative expression of a single or multiple molecule(s) on DC; (iii) examine functional consequences of the qualitative expression of a single or multiple molecule(s) on DC; (iv) generate stable and functionally-defined DC for therapeutic applications. Using this novel platform, we identified a novel mechanism utilized by the CD40 co-stimulatory molecule to define DC functional property to either tolerize or polarize an antigen-specific T cell response (2009a, manuscript in preparation). Our ability to generate tolerogenic, Th1 or Th2-polarizing DC will allow us to regulate T cell functions under different immunological disease settings. We are exploring this system further in in vivo gene therapy and HIV-1 vaccine development. The robustness of our established platform will continue to unravel novel regulatory role(s) of other previously unknown factors in DC immunobiology.
2. Molecular mechanisms underlying natural killer cell differentiation and acquisition of target specificity. Natural Killer (NK) cells are a small population of bone marrow-derived lymphocytes that provide an important line of defense against many types of microorganisms, viruses, and tumors. In a developmental process that turns hematopoietic stem cells into the specialized NK cells (termed “differentiation”), they acquire different maturation states, express different NK cell surface receptors, and become capable of distinguishing self-cells from non-self. The molecular mechanism that governs this developmental process remains unclear. This is in part due to a lack of experimental systems that allow us to differentially study a protein function(s) in primary NK progenitors, resting, and activated primary NK cells.
We demonstrated recently the successful stable transduction of genetic materials into primary mature NK cells (resting and cytokine-activated) and NK progenitors in vitro (Mol. Ther., 2007). This advancement allows us to manipulate the balance of NK receptor signaling in these NK cells (at various differentiating stages), and examine factors involved in NK differentiation. We, for the first time, demonstrated that ectopic expression of a naturally occurring NKR-P1BSJL inhibitory receptor on primary mouse NK cells is functional upon interaction with its cognate ligand on the target cells. More interestingly, over-expression of the NKR-P1BSJL inhibitory receptor is sufficient to tip the balance of signals generated from all engaged receptors on NK cell surface towards inhibition (Tran et al., Vaccines, 2010). It demonstrated the quantitative or cumulative nature of NK receptor signaling in defining functional outcomes of NK:target cell interactions. It thus provided also the proof-of-the-principle that genetic engineering of NK cells to express either natural or artificial chimeric NK receptors is a possible means to “educate” NK cells to acquire new target specificities. The ability to control the specificity of NK:target cell interactions will prove useful in future development of NK-cell based immunotherapy against tumors or virally infected cells. We will use this established platform to identify and to test novel factors involved in NK differentiation and regulation of NK cell functions. Our recent study of the SHP-1-silenced NK cells revealed a novel role for SHP-1 in maintaining NK self-tolerance in mature NK cells (2011, Mahmood et al., in preparation). In addition, we will study the role of SHP-1 in NK differentiation. We will compare phenotypes and functions of the SHP-1 silenced mature NK cells to that of the NK cells developed in the absence of SHP-1 during differentiation.
Selected Publications in the last 5 years (trainees are underlined)
Huiming Wang, Liang Zhang and Sam K.P. Kung. Genetically engineered dendritic cells in immunotherapy. (Review, Immunotherapy, 2010, Sep;2(5):685-95)
Jimmy Tran, James Carlyle and Sam K.P. Kung. Altering the specificity of NK:target cell interactions by genetic manipulation of NK receptor expression on primary mouse NK cells. (Vaccine, 2010, May 14;28(22):3767-72).
Sam K.P. Kung. Introduction of shRNAs into primary NK cellswith lentivirus. Methods Mol Biol. NK Cell Protocols, Humana Press. Editor – Dr. Kerry Campbell. 612:233-47, 2010.
Costantini JL, Cheung SM, Hou S, Li H, Kung SK, Johnston JB, Wilkins JA, Gibson SB, Marshall AJ. TAPP2 links phosphoinositide 3-kinase signaling to B cell adhesion through interaction with the cytoskeletal protein utrophin: expression of a novel cell adhesion-promoting complex in B cell leukemia. Blood, 114(21):4703-12 (2009) [contributed to the gene silencing experiments]
Liang Zhang, Tielan Fang, Michele Procuik and Sam Kam-Pun Kung. Lentiviral vectors deliver short interfering RNA into bone marrow derived dendritic cells without functional impairment. J. Immunol. Methods, 344(2):87-97 (2009) [Funded by CIHR and MHRC, contributed to the design of the experiments, writing of the manuscript.]
Tran, J. and S.K.P. Kung. Lentiviral Vectors Mediated Stable and Efficient Gene Delivery into Primary Murine Natural Killer Cells. Mol Ther Jul;15(7):1331-9. (2007) [Funded by CIHR and MHRC, contributed to the design of the experiments, writing of the manuscript.]
An D.S., X-F. Qin, V.C. Auyueng, S.K.P. Kung, D. Balitmore and Chen, I.S.Y. Optimization and functional effects of stable short hairpin RNA expression in primary human lymphocytes via lentiviral vectors. Mol Ther 14(4):494-504 (2006).
Information on Graduate Admission: