Person: Moffett, Howell Franklin
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Moffett
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Howell Franklin
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Moffett, Howell Franklin
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Publication MicroRNAs in Normal and Malignant Lymphocytes(2012-12-12) Moffett, Howell Franklin; Wucherpfennig, Kai; Hacohen, Nir; Huseby, Eric; Ventura, AndreaMicroRNAs (miRNAs) are 20-22 nucleotide non-coding RNAs that can play important roles in developmental transitions by post-transcriptional regulation of mRNA translation and stability. We profiled miRNA expression in mouse thymocytes, mature T cells, and activated T cells, and identified distinctive patterns of miRNA expression during development, maturation, and activation of T cells. The miR-128 and miR-181 miRNA families are expressed at significantly higher levels in thymocytes. Examining the expression levels of these microRNAs in more detail, we observed that the expression pattern of these microRNA families distinguishes cells committed to lymphoid lineages from cells committed to myeloid lineages during normal mouse hematopoiesis. Extending this work to human malignancies, we determine that high miR-128 expression distinguishes lymphoid precursor derived malignancies from myeloid precursor derived malignancies. Little information is available regarding miRNA expression early after CD8 T cell activation. We demonstrate dynamic miRNA expression during early CD8 T cell activation, including the repression of miR-150, miR-181a, miR-26, miR-29 and miR-30, and the induction of miR-155, miR-31, miR-146, and the miR-17-92 cluster. We show that miR-31 is induced by calcium/Calcineurin signaling during acute CD8 T cell activation, and demonstrate elevated miR-31 expression in regulatory and memory T cell populations. We identify miR-31 targets in primary CD8 T cells and propose a model where miR-31 induction primes CD8 T cells for activation by promoting T cell survival, activation, and proliferation. Activation induced miRNA expression patterns are also found in some human malignancies. Chronic lymphocytic leukemia is typically thought to be a disease of resting lymphocytes. However, we demonstrate an activated B cell miRNA expression signature in CLL. Similarities in miRNA expression between activated B cells and CLL cells include high expression of miR-34a, miR-155, and miR-342-3p and low expression of miR-103, miR-181a and miR-181b. Additionally, we show that decreased levels of miR-29c and miR-223 in CLL are negative prognostic markers associated with shorter time to first therapy. These data indicate an activated B cell status for CLL cells and suggest that the expression level of individual miRNAs may predict clinical course in CLL.Publication Unique patterns of transcript and miRNA expression in the South American strong voltage electric eel (Electrophorus electricus)(BioMed Central, 2015) Traeger, Lindsay L; Volkening, Jeremy D; Moffett, Howell Franklin; Gallant, Jason R; Chen, Po-Hao; Novina, Carl; Phillips, George N; Anand, Rene; Wells, Gregg B; Pinch, Matthew; Güth, Robert; Unguez, Graciela A; Albert, James S; Zakon, Harold; Sussman, Michael R; Samanta, Manoj PBackground: With its unique ability to produce high-voltage electric discharges in excess of 600 volts, the South American strong voltage electric eel (Electrophorus electricus) has played an important role in the history of science. Remarkably little is understood about the molecular nature of its electric organs. Results: We present an in-depth analysis of the genome of E. electricus, including the transcriptomes of eight mature tissues: brain, spinal cord, kidney, heart, skeletal muscle, Sachs’ electric organ, main electric organ, and Hunter’s electric organ. A gene set enrichment analysis based on gene ontology reveals enriched functions in all three electric organs related to transmembrane transport, androgen binding, and signaling. This study also represents the first analysis of miRNA in electric fish. It identified a number of miRNAs displaying electric organ-specific expression patterns, including one novel miRNA highly over-expressed in all three electric organs of E. electricus. All three electric organ tissues also express three conserved miRNAs that have been reported to inhibit muscle development in mammals, suggesting that miRNA-dependent regulation of gene expression might play an important role in specifying an electric organ identity from its muscle precursor. These miRNA data were supported using another complete miRNA profile from muscle and electric organ tissues of a second gymnotiform species. Conclusions: Our work on the E. electricus genome and eight tissue-specific gene expression profiles will greatly facilitate future research on determining the coding and regulatory sequences that specify the function, development, and evolution of electric organs. Moreover, these data and future studies will be informed by the first comprehensive analysis of miRNA expression in an electric fish presented here. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1288-8) contains supplementary material, which is available to authorized users.Publication A small RNA makes a Bic difference(BioMed Central, 2007) Moffett, Howell Franklin; Novina, CarlThe first highly specific knockouts of a microRNA, miR155, in mice result in multiple defects in adaptive immunity, and also show the feasibility of investigating at least some microRNAs by gene knockout.