Stephen K. Anderson, Ph.D.
The human KIR and murine Ly49 receptors for class I MHC play an important role in the development and function of natural killer (NK) cells. A major focus of the Anderson lab is unraveling the mechanisms controlling the stochastic process whereby class I receptors are expressed by subsets of NK cells. The discovery of probabilistic promoter switches in the separately evolved KIR and Ly49 gene families has produced a novel paradigm for the selective activation of genes. This paradigm has important implications for the control of stem cell fate, and the possibility of modifying differentiation outcomes in various systems.
1) molecular genetics, 2) transcriptional regulation, 3) murine Ly49 class I MHC receptors, 4) human KIR class I MHC receptors, 5) NK cell biology, 6) probabilistic promoter switches
Cellular and Molecular Studies of Cellular Cytotoxicity
The primary goal of our group is to achieve a more complete understanding of the cellular and molecular mechanisms of natural killer (NK) cell development and function. A large portion of modern cancer research has focused on the ability of the immune system to destroy cancer cells using tumor-specific antibodies and immunomodulatory agents. A better understanding of the mode of NK cell tumor recognition will allow us to design novel antitumor therapies.
The majority of our effort is directed toward the characterization of the murine Ly49 and human KIR families of NK cell receptors for class I MHC. Our lab has determined the organization of the Ly49 gene cluster in 129, BALB/c and NOD mice, demonstrating that Ly49 gene content and functional characteristics are significantly different between inbred mouse strains, analogous to the haplotype differences observed in the human KIR genes.
Our group has discovered a probabilistic transcriptional switch that controls Ly49 gene activation, and we have shown that the separately evolved human KIR gene family uses the same type of switch, indicating that probabilistic switches will likely be involved in many systems where genes are selectively activated in a subset of the cells in a given tissue. This discovery has important implications for the control of stem cell differentiation, and may one day allow us to modify cell fate in differentiating systems such as bone marrow cultures.
Collaborators on this research include Mary Carrington and Dan McVicar, NCI.
Selected Key Publications
- PLoS Genetics. 14: e1007163, 2018. [ Journal Article ]
- Genes Immun. 14: 427-33, 2013. [ Journal Article ]
Cutting edge: KIR antisense transcripts are processed into a 28-base PIWI-like RNA in human NK cells.J. Immunol. 185: 2009-12, 2010. [ Journal Article ]
Genetic control of variegated KIR gene expression: polymorphisms of the bi-directional KIR3DL1 promoter are associated with distinct frequencies of gene expression.PLoS Genet. 4: e1000254, 2008. [ Journal Article ]
Dr. Stephen Anderson is a Senior Scientist with Leidos Biomedical Research, Inc., working in collaboration with the Laboratory of Cancer Immunometabolism. He obtained his Ph.D. in 1986 from the University of Western Ontario and performed postdoctoral studies on natural killer (NK) cells at Mount Sinai Hospital in Toronto. Dr. Anderson was a project leader with the National Research Council of Canada before joining the Laboratory of Experimental Immunology at NCI in 1992.
|Frederick Joseph Goodson-Gregg||Postbaccalaureate Fellow (CRTA)|
|Hongchuan Li Ph.D.||Senior Scientist (Contr.)|
|Paul Wright||Research Associate III (Contr.)|