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X-WR-CALDESC:Events for Center for RNA Biomedicine
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DTSTART;TZID=America/Detroit:20220509T160000
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DTSTAMP:20260512T153651
CREATED:20211216T202325Z
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SUMMARY:RNA Innovation Seminar: Sika Zheng\, UC Riverside\, School of Medicine
DESCRIPTION:“Unexpected determinants of neuronal identity and properties: the curious cases of PTBP1\, PTBP2\, and neuronal splicing”\nSika Zheng\, Ph.D. \nAssociate Professor\, Director of Center for RNA Biology and Medicine\nUC Riverside\, School of Medicine \n  \nFlyer in PDF \n  \nVirtual Seminar\nZoom: https://umich.zoom.us/webinar/register/WN_dltbxWdHQ5KrC3rTl4hqLQ \nAbstract:\nAlternative splicing is the major contributor to transcriptome diversity\, but splicing is noisy and to what extend alternative splicing regulation is indispensable for biolgical processes has been controversial. Our studies have revealed the regulation and function of neural-specific splicing in shaping neuronal identity and estalishing neurons’ two unique attributes: 1. Axonogenesis (Only neurons but no other cell types have one and single axon); 2. Neuronal longevity (Neurons are the most long-lived cell types). We show that obtaining these neuronal features is coordinated by RNA binding proteins PTBP1 and PTBP2\, while PTBP1 was suggested by others to be a reprogramming factor of neuronal fate. I will discuss the regulatory mechanism of neural specific splicing underlying neurogensis and maturation. \nReferences:\nZhang M\, Ergin V\, Lin L\, Stork C\, Chen L\, Zheng S. Neuron. 2019 Feb 20;101(4):690-706.e10.\nErgin V\, Zheng S. J Mol Biol. 2020 Jun 26;432(14):4154-4166.\nZheng S. Wiley Interdiscip Rev RNA. 2020 Jul;11(4):e1585.\nLin L\, Zhang M\, Stoilov P\, Chen L\, Zheng S. Neuron. 2020 Sep 23;107(6):1180-1196.e8.\nVuong J\, Ergin V\, Zheng S. Nature Communications (accepted)
URL:https://rna.umich.edu/events/sika-zheng/
LOCATION:MI
CATEGORIES:Seminar
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DTSTART;TZID=America/Detroit:20220516T160000
DTEND;TZID=America/Detroit:20220516T170000
DTSTAMP:20260512T153651
CREATED:20220218T163352Z
LAST-MODIFIED:20220506T161447Z
UID:10130-1652716800-1652720400@rna.umich.edu
SUMMARY:RNA Innovation Seminar: Daniel O’Reilly
DESCRIPTION:“An Academic Approach to Oligonucleotide Therapeutics”\nDaniel O’Reilly Ph.D.\, MRSC\nPost-Doctoral Associate\nKhvorova Lab\nRNA Therapeutics Institute\nUniversity of Massachusetts Medical School \nFlyer in PDF \n  \nHYBRID SEMINAR:\nIn-person: BSRC\, ABC seminar rooms\nZoom: https://umich.zoom.us/webinar/register/WN_dM1a1aKVTM2KfwiieutOWg \nKeywords: Oligonucleotides\, Chemical Modifications\, RNA\, Huntington’s Disease \nAbstract: Nucleic acids (NA) are becoming the third major pillar of therapeutic modalities on par with small molecules and biologics. The diversity of NA molecular mechanisms\, ranging from vaccines\, antisense\, short interfering RNA (siRNAs)\, and guide RNA for CRISPR gene editing systems\, enable impact on most aspects of cellular biology and thus human medicine. The foundation behind the recent oligonucleotides’ clinical success is fundamental chemical innovations in RNA stability\, delivery\, and synthesis.\nOligonucleotides are informational drugs; thus\, if chemical architectures supporting safe and efficient delivery to the tissue of interest are achieved\, they can be easily reprogrammed to modulate any gene expression on demand\, creating an opportunity for academic institutions to drive therapeutic innovation. However\, the process is limited by access to oligonucleotide chemistry and synthetic expertise.\nIn the first half of the talk\, I will share the experience of building and running Nucleic Acid Chemistry Center in a context of a large academic institution. The NACC provides access to therapeutic quality screening leads and large manufacturing of preclinical compounds for the academic community. The impact of the NACC and chemical innovation will be discussed in the context of two significant projects. First\, I will discuss the systematic structure-activity relationship study of chemical modifications to modulate RISC loading and cleavage. Screening 1200 siRNA variants allow for defining the chemical and thermodynamic rules for RISC assembly.
URL:https://rna.umich.edu/events/daniel-oreilly/
LOCATION:MI
CATEGORIES:Seminar
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DTSTART;TZID=America/Detroit:20220523T160000
DTEND;TZID=America/Detroit:20220523T170000
DTSTAMP:20260512T153651
CREATED:20211206T190501Z
LAST-MODIFIED:20220519T134053Z
UID:9882-1653321600-1653325200@rna.umich.edu
SUMMARY:RNA Innovation Seminar: Analisa DiFeo & Bambarendage (Pini) Perera
DESCRIPTION:HYBRID SEMINAR:\nIn-person: BSRC\, ABC seminar rooms\nLivestream: https://umich.zoom.us/webinar/register/WN_mXMOsCvlQrSyuJQO0_EnWw \n \n“A miRNA-mediated approach to dissect the complexity of cancer progression and identify anti-cancer drugs”\nAnalisa DiFeo\, Ph.D.\nAssociate Professor\nPathology and Ob/Gyn\nMichigan Medicine \nAbstract: High grade serous carcinoma (HGSC) the most common type of “ovarian” cancer is one of the deadliest cancers diagnosed in women. One of the primary drivers for the high mortality rate associated with HGSC is tumor recurrence and chemoresistance. Thus\, there is a critical need to identify the genetic drivers of tumor development and recurrence to improve therapeutic strategies. In this proposal\, we provide extensive evidence for the clinical and biological importance of miR-181a\, which is amplified in a large majority of HGSC patients\, correlates with poor overall survival\, and induces epithelial to mesenchymal transition (EMT)\, metastasis\, drug resistance\, and stem-like cell properties. Remarkably\, this correlation between miR-181a with clinical outcome and recurrence has also been shown in numerous other cancers. Notably\, miR-181a expression in HGSC tumors offered stronger prognostic value than established clinical biomarkers. Furthermore\, analysis of >10\,000 tumors representing 20 different cancers revealed that amplification of miR-181a correlated with poor outcome. Most recently\, we have uncovered a novel mechanism through which miR-181a can drive tumor development at the earliest stage through the cooperative targeting of RB1 and Stimulator of Interferon Genes (STING). Enhanced miR-181a promoted the growth of highly aggressive and genomically instable cells through the direct inhibition of STING\, a key activator of interferon signaling in response to cytoplasmic DNA. Though activating anti-tumor immunity is increasingly being recognized as an important therapy in cancer treatment the efficacy of current immunotherapies for the treatment of HGSC has not been successful mainly due to the highly immunosuppressive microenvironment. One of the primary means by which a tumor creates an immunosuppressive microenvironment is by inhibiting STING signaling within the tumor. Thus\, our novel finding showing that miR-181a directly regulates STING introduced unique opportunity to assess whether therapeutic targeting of the miR-181a will reactivate IFN signaling via STING to overcome immune tolerance that is commonly seen in HGSC tumors. \n  \n\n“The Role of piRNA in Environmental Epigenetics”\nBambarendage Pinithi Perera\, Ph.D.\nResearch Assistant Professor\nEnvironmental Health Sciences\nSchool of Public Health \nKeywords: piRNA\, epigenetics\, toxicology \nAbstract: Piwi-interacting RNAs (piRNAs) are small non-coding RNAs that associate with PIWI proteins to induce DNA methylation for retrotransposon suppression. Mature germline piRNAs typically consist of 24–32 nucleotides with a strong preference for a 5ʹ uridine\, an adenine at position 10\, and a 2ʹ-O-methylated 3ʹ end. In the current study\, we identified piRNAs and associated machinery from mouse somatic tissues by quantifying Piwil1\, Piwil2\, and Piwil4 expression in brain\, liver\, kidney\, and heart. The study revealed 26 piRNA sequence species and 40 piRNA locations exclusive to all examined somatic tissues. Non-coding RNA expression is sensitive to environmental exposures\, although it has been unclear whether exposures such as lead (Pb) impact piRNA expression. In the current study\, mouse dams were exposed to Pb 2 weeks prior to mating which continued through offspring weaning. We profiled tissue- and sex-specific effects of perinatal Pb exposure on the piRNA transcriptomes of the resulting progeny at 5 months. Based on significant p-values (<0.05)\, 346 piRNAs were differentially expressed among Pb-exposed mice in testes\, 339 in ovaries\, 127 in M cortex\, 105 in F cortex\, 42 in M liver\, and 59 in F liver. According to preliminary results\, a total of 3 piRNAs were\ndifferentially expressed based on FDR(q<0.05). Although piRNA expression has long been considered exclusive to the germline\, our results support previous reports of somatic piRNA expression\, and demonstrate that perinatal environmental exposures such as Pb influence longitudinal piRNA expression in a tissue- and sex-specific manner. \n  \n 
URL:https://rna.umich.edu/events/difeo-and-perera/
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