2017 The Christina Fleischmann Award to Young Women Investigators
2017 The Christina Fleischmann Award to Young Women Investigators

2017 The Christina Fleischmann Award to Young Women Investigators

Susan Carpenter, Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz., Santa Cruz, United States

Dr. Susan Carpenter received her Ph.D. from Trinity College Dublin, Ireland for her work on the identification of a novel protein named TRIL and its role as a co-receptor in Toll like receptor signaling.  Dr. Carpenter obtained a prestigious Health research board/Marie Curie fellowship to carry out her postdoctoral work in the laboratory of Dr. Kate Fitzgerald at UMASS Medical School where she began to investigate the role of long noncoding RNAs (lncRNAs) within the innate immune system. Her published work (Science, 2013) provided the first evidence that a lncRNA (lincRNA-Cox2) could function to control innate immune genes. She completed her postdoctoral work at the laboratory of Dr. Michael McManus at the University of California, San Francisco where she worked on developing high throughput genomic approaches to study lncRNAs important for human innate immune signaling in host defense. Dr. Carpenter started her independent research group at the University of California, Santa Cruz in 2015 where they focus on the identification of novel genes involved in regulating the inducible inflammatory response. This is achieved through the use of high throughput Cas9 screening techniques in addition to more focused approaches generating animal models to study specific lncRNA genes and their roles in host defense against infection and inflammatory diseases. Her work has been supported by the Arthritis National Research Foundation where she was named the Sontag Foundation Fellow in 2014 and the James Klinenberg Scholar in 2016. The long-term goals of the Carpenter Lab are to provide critical and novel insights into how immune cells develop and respond during infection with the aim to identifying novel drug targets leading to improved therapeutics for infectious and inflammatory diseases.

Abstract from Cytokines 2017 in Kanazawa, Japan:

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.