4214A Biochemical Sciences Building
440 Henry Mall
Madison, WI 53706
• B.Eng. + M.Eng., Technical University of Denmark
• Ph.D, European Bioinformatics Institute, University of Cambridge
• Postdoctoral Fellow at the Fred Hutchinson Cancer Research Center
Honors & Awards
• European Molecular Biology Laboratory Predoctoral Fellow
• Department of Defense Breast Cancer Program Postdoctoral Fellow
Pre-mRNA splicing is essential to all human cells, but dys-regulated splicing factors can act as tumor suppressors or oncogenes across many tumor types. Our previous work has demonstrated that RNA mis-splicing is a common feature of cancer, even in the absence of currently known genetic drivers of splicing misregulation. However, in most cases the causes and consequences of aberrant splicing remain poorly understood. In our lab we study the full spectrum of RNA splicing, from splicing mechanisms to protein isoform activity, to address the following understudied areas:
• RNA splicing is modulated by a range of spliceosomal proteins and co-factors, but the non-coding components of the splicing machinery constitute an uncharacterized layer of regulation.
• Splicing changes can be accurately detected genome-wide, but it remains unclear which isoforms are eventually translated, and hence which RNA splice variants to prioritize for functional studies.
• The function, activity, and clinical implications of individual splice variants remain largely unknown, as exemplified by protein isoforms of key cancer genes.
Our goal is to address these gaps in our understanding of how RNA splicing acts as a disease mechanism, with the ultimate aim of understanding how dysregulation of the transcriptome contributes to cancer initiation, progression and response to therapies, and translating these findings into clinical advances. To achieve this, we use a range of complementary experimental and computational approaches.
Postdoctoral, PhD students, MD/PhD students, and undergraduates interested in pursuing research in the laboratory should contact Dr. Dvinge directly at email@example.com
Publications of Note
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• Uo T, Dvinge H, Sprenger CC, Bradley RK, Nelson PS, Plymate SR. Systematic and functional characterization of novel androgen receptor variants arising from alternative splicing in the ligand-binding domain. Oncogene. 2017 Mar;36(10):1440-1450. PubMed PMID: 27694897.
• Dvinge H, Kim E, Abdel-Wahab O, Bradley RK. RNA splicing factors as oncoproteins and tumour suppressors. Nat Rev Cancer. 2016 Jul;16(7):413-30. PubMed PMID: 27282250.
• Lee S, Dvinge H, et al. Modulation of splicing catalysis for therapeutic targeting of leukemia with mutations in genes encoding spliceosomal proteins. Nature Medicine 2016. 22(6):672-678. PubMed PMID: 27135740
• Dvinge H, Bradley RK. Widespread intron retention diversifies most cancer transcriptomes. Genome Med. 2015;7(1):45. PubMed PMID: 26113877.
• The Molecular Taxonomy of Primary Prostate Cancer. Cell. 2015 Nov 5;163(4):1011-25. PubMed PMID: 26544944.
• Robinson D, et al. Integrative clinical genomics of advanced prostate cancer. Cell. 2015 May 21;161(5):1215-28. PubMed PMID: 26000489.
• Hickey TE, et al. Expression of androgen receptor splice variants in clinical breast cancers. Oncotarget. 2015 Dec 29;6(42):44728-44. PubMed PMID: 26554309.
• Dvinge H, et al. Sample processing obscures cancer-specific alterations in leukemic transcriptomes. Proc Natl Acad Sci U S A. 2014 Nov 25;111(47):16802-7. PubMed PMID: 25385641
• Dvinge H, Git A, et al. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 2013 May 16;497(7449):378-82. PubMed PMID: 23644459.
• Git A, Dvinge H, Salmon-Divon M, et al. Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA. 2010 May;16(5):991-1006. PubMed PMID: 20360395.