|
|
Ole Gjoerup, Ph.D.
|
Assistant Professor
1.8 HCCLB
5117 Centre Avenue
Pittsburgh, Pennsylvania 15213
Phone: (412) 623-7717
Fax: (412) 623-7715
E-mail: ovg27@pitt.edu
Lab Phone:
Lab Website
|
|
|
|
Research
My research career is founded on using papovaviruses to understand fundamental cellular processes. Because of their small coding capacity, DNA tumor viruses are entirely dependent on commandeering the host cell machinery for replication. Their subversion of cellular mechanisms in order to make this happen is similar to the breakdown of cellular control mechanisms occurring in human tumor cells. Studies on these viruses have identified both positive and negative control elements, identifying tyrosine phosphorylation, PI3 kinase and p53 as pivotal features of cellular regulation. My graduate studies concerned the functional characterization of mouse polyomavirus large T antigen (LT), showing how independent domains were coordinated to regulate viral DNA replication and to control host cell growth. My earlier postdoctoral studies concerned the cell death program induced by SV40 small t antigen and also parsing out the cellular pathways used by small T in the induction of tumorigenesis in human cells. My current research has centered on the use of LT from the SV40 DNA tumor virus to identify and understand the workings of critical targets in cell cycle and checkpoint control and how these interface with oncogenesis. LT has provided valuable model systems for tumor induction in a wide variety of tissues including pancreas and prostate. From the genetics, it is clear that the viruses have much more to teach us about cell regulation. Through mutant analysis, I have identified a novel target of LT, namely the Bub1 spindle checkpoint kinase, thereby linking LT for the first time to the host mitotic machinery. Bub1 is evolutionarily conserved and regulates the mitotic spindle checkpoint, surveying proper chromosome segregation as part of a cellular “quality control” mechanism. Importantly, Bub1 has been found mutated occasionally in colorectal cancers characterized by aneuploidy. My genetic analysis based on LT mutants implicates Bub1 binding in an array of functions including LT-mediated oncogenic transformation, viral replication and conversion of human fibroblasts to tetraploidy. I am interested in understanding the mechanisms connecting Bub1 to viral transformation. I am also committed to examining its function in signaling in cancers that do not arise from viral infections. It is my firm belief that the study of LT interactions with the mitotic machinery will yield a rich vein of information on cell cycle regulation in normal and tumor cells.
|
|
Selected Publications
- Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat PS, Roberts TM, Gjoerup OV. 2009. "Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding" J Virol. 83:117-27. | Abstract
- Andrabi S, Gjoerup OV, Kean JA, Roberts TM, Schaffhausen B. 2007. "Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner" Proc Natl Acad Sci USA 104:19011-6. | Abstract
- Williams GL, Roberts TM, Gjoerup OV. 2007. "Bub1: escapades in a cellular world" Cell Cycle 6:1699-704. | Abstract
- Lock RL, Szeto TH, Entwistle A, Gjoerup OV, Jat PS. 2007. "Preparation of monoclonal antibodies against the spindle checkpoint kinase Bub1" Hybridoma 26:140-7. | Abstract
- Gjoerup OV, Wu J, Chandler-Militello D, Williams GL, Zhao J, Schaffhausen B, Jat PS, Roberts TM. 2007. "Surveillance mechanism linking Bub1 loss to the p53 pathway" Proc Natl Acad Sci USA. 104:8334-9. | Abstract
- Zhao JJ, Cheng H, Jia S, Wang L, Gjoerup OV, Mikami A, Roberts TM. 2006. "The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation" Proc Natl Acad Sci USA. 103:16296-300. | Abstract
- Kaur R, Liu X, Gjoerup O, Zhang A, Yuan X, Balk SP, Schneider MC, Lu ML. 2005. "Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP kinase" J Biol Chem. 280:3323-30. | Abstract
- Zhang L, Gjoerup O, Roberts TM. 2004. "The serine/threonine kinase cyclin G-associated kinase regulates epidermal growth factor receptor signaling" Proc Natl Acad Sci USA. 101:10296-301. | Abstract
- Cotsiki M, Lock RL, Cheng Y, Williams GL, Zhao J, Perera D, Freire R, Entwistle A, Golemis EA, Roberts TM, Jat PS, Gjoerup OV. 2004. "Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1" Proc Natl Acad Sci USA. 101:947-52. | Abstract
- Zhao JJ, Gjoerup OV, Subramanian RR, Cheng Y, Chen W, Roberts TM, Hahn WC. 2003. "Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase" Cancer Cell 3:483-95. | Abstract
|
|
|
