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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

I trained in biochemistry and virology and learned classical Sanger sequencing as a fellow at the NIH and Maxim-Gilbert rapid sequencing as a starting faculty member. I came to Duke University in 1979 because of my interest in virus-host interactions, virus genomes, and regulatory mechanisms of RNA biology. I participated in many collaborative projects over the years and after cloning cDNAs encoding several RRM-autoimmune antigens I came to focus more on the host than the virus. While I have had many gratifying collaborations with clinical faculty my current focus is with liver specialist Anna Mae Diehl and colleagues. Thus, I am fully committed to fundamental basic research and underlying mechanisms of gene expression in liver. I have served on many study sections, review panels and editorial boards as I have a strong dedication to public service and supporting our funding agencies. To briefly summarize the highlights my research: we were first to clone of a RNA-binding protein, La (1985), and thereby discovered the RRM family proteins. We devised novel methods to study mechanistic protein-RNA interactions (1984-90), discovered low complexity repeats in U1-70k RBP (1989) that liquid-coalesced in the nucleus, cloned ELAVL2 RBP (1990), inhibited splicing and nuc-cyto export (1994-95), first to demonstrate multi-targeting of a RNA binding protein other than polyA-binding protein (1993-94), and to that end we invented the RIP and CLIP methods (1999) that allowed us to discover RNA regulons (2000-present), demonstrated quantitative changes in RBP binding site strength across entire transcriptome (2010-2017), demonstrated RAS protein activates post-transcriptional events leading to malignant invasive phenotype (2018). RNA operon/regulon 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 example, 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) Importantly, many 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 RBP 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 overall goals, for example, are to understand the role of post-transcriptional regulation in normal and diseased states (e,g, dis-coordinated) in order to identify, target, and/or remodel RNA regulons by manipulating underlying mechanisms of liver regeneration and/or liver diseases such as cirrhosis.

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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 San Diego, CaliforniaSan Diego,