The importance of natural killer cell and dendritic cell in recognition of foreign microorganisms and regulation of immune responses has been well established. As these two cellular components are critical regulators of innate and adaptive immunity, a better understanding of innate immunity will also provide new insights into protocols that enable us to modify immune responses in clinically relevant immune disorders or for prophylaxis. The CFI-funded Laboratory of Innate Immunobiology is a cellular and molecular immunology laboratory dedicated to the studies of the molecular mechanisms underlying NK and DC differentiation and functional development. We developed lentiviral vectors for stable genetic modifications of primary cells to better understand protein functions at different differentiation states, and for gene therapy applications.

Differentiation and Molecular Definition of DC effector functions. Dendritic cells (DC) are professional antigen presenting cells (APC) that initiate and regulate immune responses. They are capable of sensing environmental stimuli, processing and presenting antigen to T cells, and undergoing a maturation program that is critical in controlling T cell immunity versus tolerance. Phenotypic analysis of the surface expression of co-stimulatory molecules has been used routinely in defining immature and mature DC, terms that are often used interchangeably with tolerogenic and immunogenic DC respectively. The increasing number of co-stimulatory molecules identified to date highlights the importance and complexity of co-stimulatory signals in defining DC functions. Our current interests include: 1. To test the hypothesis that quantitative expression levels of CD40 on DC are pivotal in determining the different functional properties of DC to tolerize, activate or polarize antigen-specific Th1/Th2 immune responses in vivo. 2. To identify factor(s) involved in DC differentiation and maturation process.

Molecular mechanism underlying NK differentiation and acquisition of target cell recognition 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 tumor. 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. Our research program will study cellular factors and molecular signaling involved in NK differentiation and target recognition. Our current interests include: 1. To use the NKR-P1B inhibitory receptor/ligand as a model receptor to formally examine the quantitative importance of the NK inhibitory receptor NKR-P1B and SHP-1 phosphatase signal transducer in regulating NK development and NK target recognition. 2. To examine functions and differentiation of unique NK subsets in lymph nodes.

Recent Publications:

Kung publications on PubMed

NB: Dr. Kung is in the process of establishing his lab and is actively seeking graduate students and a technician. If you are interested in studying with Dr. Kung, or working in his lab, please contact him directly at (204) 480-1301 or kung@cc.umanitoba.ca"