Lieping Chen, MD, PhD - Research
Interests
Molecular description of leukocyte activation and deactivation;
biochemical, structural and functional aspects of lymphocyte
co-signal molecules; immunology and immunotherapy of cancer,
autoimmune diseases, viral infection and transplantation
rejection.
A successful immune response consists of highly orchestrated
cellular and molecular events. In cellular level, a pathogen
will first alert a set of so-called antigen-presenting cells
(APC), including dendritic cells and macrophages, leading to
stimulation of adaptive components of immune systems including
T lymphocytes. Upon elimination of pathogen, expanded T cells
contract to basal level. In molecular level, a pathogen is
processed by APC and presented in the groove of the major histocompatibility
complex (MHC) to T cells with specific receptor (TCR) to initiate
intracellular activation program. Outcome of TCR signal, however,
is largely determined by a group of co-signal molecules which
are also presented on APC and T cells.
Research focus of our laboratory is to identify and characterize
co-signal molecules which play key roles in the control of
T cell activation and deactivation. Co-signal molecules are
essential for the communication of a T cell with virtually
all other host cells. During cell-cell contact, specific recognition
occurs between co-signal molecules and triggers biochemical
signaling, which leads to cascades of transcription and expression
of downstream genes in the nucleus. Therefore, co-signaling
molecules are among the earliest responding elements of the
immune system to antigens. A hallmark for co-signal molecules
is that their functions are entirely dependent on TCR signals
and the role of co-signal molecules is to control the TCR signal.
In the absence of sufficient TCR signaling, co-signal molecules
lose their function or function aberrantly. The majority of
co-signal molecules are members of the immunoglobulin (Ig)
and tumor necrosis factor (TNF) superfamilies. Based on the
functional outcomes, co-signal molecules can be further categorized
as costimulators or positive costimulatory molecules that enhance
TCR-mediated responses, and coinhibitors or negative costimulatory
molecules that inhibit TCR-mediated responses.
The main interest of our laboratory is biochemical, structural
and functional studies of co-signal molecules. We are also
interested in defining signaling events that induces activation
and deactivation of naïve and mature effector T cells.
By precise manipulation of these cell surface molecular pathways,
we hope to develop new strategies to treat cancer, autoimmune
diseases, viral infection and transplantation rejection.
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