|
Stephan Gasser
BSc (Hons), PhD
Assistant Professor, Immunology Programme
Department of Microbiology
Tel: +65 6516 7209
Email: micsg@nus.edu.sg |
|
|
 |
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. |
| |
 |
|
Gasser S (2007) DNA damage response and development of targeted cancer treatments. Annals of Med. 31:1-8
Gasser S and Raulet DH (2006) Activation and self-tolerance of natural killer cells. Immunol. Rev. 214:130-142
Gasser S and Raulet DH (2006) The DNA damage response, immunity and cancer. Sem. Cancer Biol. 16:344-347
Gasser S and Raulet DH (2006) The DNA damage response arouses the immune system. Cancer Research. 66:3959-3962
Bianchi T, Gasser S, Trumpp A and MacDonald HR (2006) c-myc acts downstream of IL-15 in the regulation of memory CD8 T cell homeostasis. Blood. 107:3992-3999
Gasser S, Orsulic S, Brown EJ and Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nat. 436 7054:1186-1190
Carlyle JR, Jamieson AM, Gasser S, Clingan CS, Arase H and Raulet DH (2004) Missing self-recognition of Ocil/Clr-b by inhibitory NKR-P1 natural killer cell receptors. Proc. Natl. Acad. Sci. 101:3527-3532
Trumpp A, Refaeli Y, Oskarsson T, Gasser S, Murphy M, Martin GR and Bishop JM (2001) c-Myc regulates mammalian body size by controlling cell number but not cell size. Nat. 414:768-773
Gasser S, Corthesy P, Beerman F, MacDonald H R and Nabholz M (2000) Constitutive expression of a chimeric receptor that delivers IL-2/IL-15 signals allows antigen-independent proliferation of CD8+CD44high but not other T cells. J. Immunol. 164:5659-5667 |
|
 |
|
|
| |
|
|
