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SELECTBIO Conferences Extracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics

Jack Keene's Biography

Jack Keene, James B. Duke Professor, Duke University Medical Center

Education: University of California, Riverside 1969; PhD in Microbiology and Immunology, University of Washington, Seattle 1974. I trained in biochemistry and virology as a fellow at the NIH 1974-1978 where I learned classical Sanger sequencing and Maxim-Gilbert rapid sequencing of virus genomes. Joined the faculty Duke University Medical Center in 1979 as Assistant Professor of Microbiology and Immunology, with interest in virus-host interactions, virus genomes, and regulatory mechanisms of RNA biology. Professor and Chairman of Microbiology (1992-2002). James B. Duke Distinguished Professor 1994-Present.

Highlights of research: My lab was first to clone a sequence specific RNA-binding protein, La (1985), and thereby discovered and named the RNA Recognition Motif (RRM) and RRM family proteins (1988-1989). We devised novel methods to study mechanisms of protein-RNA interactions (1984-90), discovered low complexity repeats in U1- 70k RBP (1989) that caused liquid-coalesced in the nucleus, cloned ELAVL2 (HuB) RBP (1990), and showed that low complexity repeats inhibited splicing and nuclear export (1994-95). We were first to demonstrate multi-targeting of a RNA binding proteins (1993-94), and to that end we invented the RIP and CLIP methods (1999) that allowed us to discover RNA regulons (2000-present). We then demonstrated quantitative changes in RBP binding site strength across the entire transcriptome (2010-2017), and demonstrated RAS protein activates post-transcriptional events leading to malignant invasive phenotype (2018).

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Coordination of Functionally Related mRNAs and Proteins in Granules, GW/P bodies, and Vesicles

Friday, 26 February 2021 at 09:00

Add to Calendar ▼2021-02-26 09:00:002021-02-26 10:00:00Europe/LondonCoordination of Functionally Related mRNAs and Proteins in Granules, GW/P bodies, and VesiclesExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual

Gene expression is determined by transcriptional and post-transcriptional mechanisms that coordinate regulatory layers and are localized in many cellular sub-environments. Post-transcriptional regulatory layers consist of trans RNA-binding proteins and multiple copies of cis messenger RNAs (mRNAs) and noncoding RNAs (miRNAs and other ncRNAs) that together form modular RNA regulons (RBPs) that in turn, coordinate the latter state of gene expression on a global level. The multi-targeting of mRNAs in RNA regulons include cis binding sites that are: a) RBP sequence specific, b) miR binding sites, c) modified mRNAs (e.g. methylated), that together produce functionally related proteins that can be found in cellular vesicles, bodies or granules by translation. Thus, RNA regulons are found in nearly all species and coordinate RNA turnover, localization, and/or translation globally in response to biological activation or repression. RNA regulons have myriad ramifications for biological coordination. Over time, dozens of RNA regulons have been reported in many biological systems and in dozens of species. For examples from the field: 1) PUF RNA regulons coordinate fungal metabolism and pathogenesis dating back over 500 million years; 2) trypanosome RNA regulons coordinate parasite differentiation in the blood at a time when transcription is silenced. 3) dozens of mammalian RNA regulons have biological and physiological ramifications in which mRNAs encoding functionally related proteins bound to several of the ~1,500 RBPs now known RBPs. Thus, RNA regulons can efficiently utilize and locate protein building blocks and regulatory factors that function as complex traits. Moreover, these overlapping mRNA subsets are highly dynamic and responsive to intrinsic and extrinsic signals. To understand these dynamic processes our lab developed Digestion Optimized-RIP-seq that is quantitative and applicable to understanding how combinatorial mechanisms regulate dynamic coordination of RNA targets during growth and differentiation, as well as revealing novel RNA regulons in cancer, neurodegeneration and liver development/regeneration. Our goal is to teach these technologies to students and fellows in order to decipher the remodeling of RNA regulons so to reveal underlying mechanisms of disease.

Add to Calendar ▼2021-02-25 00:00:002021-02-26 00:00:00Europe/LondonExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and TherapeuticsExtracellular Vesicles (EV)-Exosomes: Diagnostics, Delivery and Therapeutics in Virtual ConferenceVirtual