Human Oncology Department
DNA repair; gene expression; neurodegeneration; amyotrophic lateral sclerosis
3059 Wi Institute Medical Research
1111 Highland Ave
Madison, WI 53705
Cancer Biology; Membrane Biology & Protein Trafficking; Cellular & Molecular Metabolism
Research in my lab follows three main themes: (i) Phosphoregulation by CREB/ATF transcription factors and its contributions to gene expression, genotoxic stress response, and cell growth regulation; (ii) mechanisms of RIF1 (Rap1-interacting factor) alternative splicing and its implications for genome protection; and (iii) genetic models of UBQLN2-associated ALS. In the first project we have outlined a novel mechanism of phosphorylation-dependent CREB autoinhibition and are using mouse models to ascertain how defects in autoinhibition contribute to growth deregulation of cancer cells. In the second project we are investigating how alternative splicing of RIF1 influences its participation in DSB repair and replication timing regulation. As part of this project we have generated RIF1-isoform mutant mice that may serve as novel models for genome instability. RIF1 and CREB-related projects both rely on CRISPR/CAS9-based approaches to generated novel functional alleles. Finally, our third area of study is centered on the ubiquitin chaperone protein, UBQLN2, which is mutated in familial forms of ALS. In addition to studying biochemical impacts of UBQLN2 mutations we have generated Drosophila models to identify intramolecular determinants of UBQLN2 toxicity and identify disease-relevant modifier pathways.