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Research
Interests
The innate immune
system provides a first line of defense against infections,
microorganisms, and tumors. In addition, it is required to induce
and enhance adaptive immune responses. The mechanisms that govern
the recognition of pathogens and tumor cells by the innate immune
system have been elusive. First insights into the nature of innate
immune
recognition were provided by the molecular characterization of
receptor/ligand systems. Toll-like receptors and NOD proteins
recognize bacterial and viral products. Other receptors, such as
NKG2D, recognize self-molecules that are specifically expressed on
diseased cells. The regulation of disease-induced self-ligand
expression is not well understood. Our research focuses on
understanding the molecular mechanisms underlying these processes.
Recently we have discovered that the
DNA damage response regulates the expression of NKG2D ligands. The
DNA damage response, which detects and protects against DNA lesions,
is often induced by genomic abnormalities in infected and tumor
cells. Genotoxic stress could therefore represent distinctive
feature of diseased cells and may provide a means for the immune
system to recognize diseased cells.
A major
focus of our research is to identify DNA damage induced
immunomodulatory molecules; reveal mechanisms whereby the DNA damage
response activates the expression of immunomodulatory molecules;
assess the functional consequences of DNA damage induced
immunomodulatory molecules in different diseases and study how the
immune system manipulates the DNA damage response. This unique arm
of the DNA damage response may have implications in understanding
therapeutic agents, many of which induce the DNA damage response,
and for designing more effective regimens to treat cancer and
infections.
Representative Publications
1. Gasser
S,
Raulet DH. Activation and self-tolerance of natural killer cells.
Immunol Rev. 2006 Dec; 214: 130-42.
2. Gasser
S,
Raulet DH. The DNA damage response, immunity and cancer.
Sem Cancer Biol.
2006 Oct;16 (5):344-7.
3. Gasser
S,
Raulet DH. The DNA damage response arouses the immune system. Cancer
Res. 2006 Apr. 15, 66: 3959-62.
4. Bianchi
T, Gasser S, Trumpp A, MacDonald HR. c-myc acts downstream of
IL-15 in the regulation of memory CD8 T cell homeostasis.
Blood.
2006 May;107 (10):3992-9.
5. Gasser
S,
Orsulic S, Brown EJ, Raulet DH. The DNA damage pathway regulates
innate immune system ligands of the NKG2D receptor. Nature. 2005
Aug; 436 (7054): 1186-90.
6. Carlyle
JR, Jamieson AM, Gasser S, Clingan CS, Arase H, Raulet DH.
Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural
killer cell receptors. Proc Natl Acad Sci USA. 2004 Mar 9; 101 (10):
3527-32.
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