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Complexity of gene output

The realization that most human genes generate multiple mRNAs encoding divergent protein isoforms via alternative splicing and polyadenylation has revealed extensive regulation that remains to be explored.

Alternative pathways of RNA processing are regulated in response to signaling cues often coordinating expression of gene networks in response to physiological change including in development and disease.

We are interested in understanding the mechanisms and consequences of this regulation, from how RNA binding proteins and signaling pathways coordinate RNA processing networks to the functional consequences of the different protein isoforms that are expressed in different cell states.

We also investigate the pathogenic mechanisms of myotonic dystrophy, type 1 (DM1), an autosomal dominant neuromuscular disorder affecting multiple tissues including muscle, heart and the central nervous system. The pathogenic mechanism is disruption of developmentally regulated RNA processing, primarily alternative splicing, in which failure to express adult splicing patterns causes primary features of the disease.

The understanding of the molecular mechanisms of DM1 pathogenesis has led to development of several therapeutic approaches some of which are being testing using mouse models established in the lab.

These investigations utilize a combination of cell culture and genetic models including transgenic and knock out mouse lines for RNA binding proteins, CRISPR-derived mouse lines in which specific alternative exons are removed, and DM1 mouse models.

The overlapping areas of investigation in the lab lead to synergistic and collaborative interactions in which knowledge gained in one area fosters progress in the others.

Cooper Lab News

- Ashish Rao was awarded a two-year predoctoral fellowship from the Myotonic Dystrophy Foundation starting January 2018. Ashish also received a travel award to attend the 14th Annual Meeting of the Oligonucleotide Therapeutics Society in Seattle, Wash. in October, 2018.

- Paul Pang’s manuscript describing consequences of CRISPR-mediated redirected splicing of Scn5a in mice was published in the Journal of the American Heart Association, 2018. Paul was awarded a three-year predoctoral F31 NRSA fellowship from the NIH to start in 2018. Paul also received the 2018 Claude W. Smith Award for research accomplishments from the IMBS graduate program. Paul won best poster award at the 2019 IMBS graduate program annual retreat.

- Ravi Singh’s paper describing the effect of Rbfox1 and 2 double knock out in skeletal muscle was published in Cell Reports June, 2018. Ravi accepted a tenure track assistant professor position at the Medical College of Wisconsin, Milwaukee beginning October, 2018.

- Diana Cox was awarded a three-year predoctoral F31 NRSA fellowship from the NIH to starting in 2018. Diana also won a poster award (with funds for partial travel reimbursement) at the 2018 Post-transcriptional Gene Regulation Gordon Research Conference. Diana won first place for the 3MT Three Minute Thesis competition sponsored by Queensland University.

- Ginny Morriss’ paper describing the DM1 mouse model was published in Human Molecular Genetics 2018. Ginny has accepted a tenure track assistant professor position at the University of Mary Washington in Fredericksburg, Va.