2017 Christina Fleischmann Award to Young Women Investigators

Susan Carpenter
Christina Fleischmann Award to Young Women Investigators

A long noncoding RNA regulates the switch between macrophage differentiation and inflammation, Susan Carpenter1, Sergio Covarrubias1, Sol Katzman1, Ran Song2, Edward Wakeland2; 1Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz., Santa Cruz, United States, 2Department of Immunology, UT Southwestern Medical School, Dallas, United States

Macrophages are critical effector cells of the innate immune system essential for controlling infection and maintaining tissue homeostasis. At the cellular level, pathogen-response involves recognition by Toll-like receptors (TLRs) and complex intracellular signaling cascades that result in induction of an inflammatory program. Perturbations to these signaling pathways can have devastating consequences, leading to diseases, such as Rheumatoid Arthritis and Cancer. Macrophages arise from monocytes in a differentiation process that is tightly regulated, involving many microRNAs, proteins and stage-specific expression of transcription factors. Long non-coding RNAs (lncRNAs) represent the largest group of RNA produced from the genome and are described as transcripts greater than 200 nucleotides in length that lack protein-coding ability. LncRNAs are rapidly emerging as critical regulators of a broad range of biological processes including genomic imprinting, development, and cancer. We sought to identify novel lncRNAs involved in monocyte to macrophage differentiation. We generated comprehensive RNA-sequencing data sets from primary healthy human monocytes, differentiated macrophages and identified hundreds of lncRNAs differentially expressed during differentiation. We characterized one lncRNA, called GAPLINC, which is dramatically induced over one-thousand-fold transitioning from monocyte to macrophages. GAPLINC is localized to the cytoplasm, but does not associate with polysomes. Interestingly, this lncRNA is rapidly downregulated upon TLR stimulation suggesting a connection to inflammatory pathways. Knocking down GAPLINC in primary human macrophages results in up-regulation of inflammation-related genes, suggesting this lncRNA may negatively regulate inflammatory pathways. Overexpression of GAPLINC suppresses the inflammatory response and promotes proliferation. Here we reveal an intriguing role for a lncRNA in regulating the switch between macrophage differentiation/proliferation and the downstream inflammation pathways.

Christina Fleischmann
Award to Young Women Investigators
The rules for this ICIS award are the same as for the Milstein Young Investigator Award (see above) except for gender and the candidate must have received a Ph.D or M.D. degree within the previous 10 years. This award is made possible through the generosity of the Fleischmann Family and is dedicated to the memory of ISICR member and outstanding interferon research scientist Christina Fleischmann. This award is open to young women investigators working in the cytokine, chemokine and interferon biology. 2016 Dr. Christina Fleischmann Award Winner