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Peter Thorpe

Columbia University Medical Center
College of Physicians & Surgeons
Department of Genetics & Development
701 West 168th Street
Hammer Building, Room 1606
New York, NY
10032 USA
Tel. +1 212 305 1734
Fax. +1 212 923 2090
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Rothstein
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I am an associate research scientist in Rodney Rothstein's laboratory at Columbia University, located within the Medical Center at 168th Street in New York City. I have developed a new model of asymmetric cell division, a process that is essential for establishing diverse cell lineages during the development of complex organisms. This pattern of cell division continues to be crucial in the adult, where stem cell populations undergo repeated asymmetric divisions in order to both maintain a stem cell lineage and simultaneously replace differentiated cells. I have also developed novel, powerful high-throughput microscopy tools to rapidly screen the localization, levels and dynamics of any yeast protein in a library of nearly 5000 gene deletions and integrate them into a visual dataset of proteomic interactions. We are now employing high-throughput microscopy screens to identify the genes responsible for asymmetric cell division and kinetochore function. A long-term and ambitious goal is to construct a systems-level microscopy dataset comprising images that describe the localization and concentration of every yeast protein, at every point of the cell cycle and in every viable yeast mutant, linked to other systems level yeast data.



Publications

16. Thorpe, P.H. Bruno, J. Rothstein, R. 2009. Kinetochore asymmetry defines a single yeast lineage. Proc. Natl. Acad. Sci. USA 106; 6673-6678.
15. Thorpe, P.H. Bruno, J. Rothstein, R. 2008. Modeling Stem Cell Asymmetry in Yeast. Cold Spring Harb. Symp. Quant. Biol. 73; 81-88.
14. Thorpe, P.H. González-Barrera, S. and Rothstein, R. 2007. More is not always better: the genetic constraints of polyploidy. Trends in Genetics 6; 263-266.
13. Cagney, G. Alvaro, D. Reid, R.J. Thorpe, P.H. Rothstein, R. and Krogan, N.J. 2006. Functional genomics of the yeast DNA-damage response. Genome Biol. 7: 233.
12. Thorpe, P.H. Marrero, V.A. Savitzky, M.H. Sunjevaric, I. Freeman, T.C. and Rothstein, R. 2006. Cells expressing murine RAD52 splice variants favor sister chromatid repair. Mol. Cell Biol. 26; 3752-3763.
11. Simpson, A.J. King, J.A. Thorpe, P.H. McLachlan, G. and Sallenave, J-M. 2004. Towards gene therapy for inflammatory and infective pulmonary diseases. Current Genomics. 5; 365-383.
10. Thorpe, P. Stevenson, B.J. and Porteous D.J. 2002. Optimising gene repair strategies in cell culture. Gene Therapy 9; 700-702.
9. Thorpe, P.H. Stevenson, B.J. and Porteous D.J. 2002. Functional correction of episomal mutations with short DNA fragments and RNA-DNA oligonucleotides. J. Gene Medicine 4; 195-204.
8. Thorpe, P.H.; Stevenson, B.J.; and Porteous D.J. 2002. Analysing Mammalian Gene Repair Using GFP. Mol. Ther. 5;402 p.S132.
7. Thorpe, P.H.; Stevenson, B.J.; and Porteous, D.J. 2001. Comparing two strategies for functional gene correction. Mol. Ther. 3;1143 p.S401.
6. Thorpe, P.H.; Stevenson,B.J.; Gohil, A; and Porteous, D.J. 2000. Towards CFTR Gene Correction: A Comparison of two key strategies. Pediatric Pulmonology S20; (244) p.241.
5. Thorpe, P.H. and Porteous, D.J. 1999. Rapid quantitation of gene therapy specific CFTR expression using the Amplification Refractory Mutation System. Biotechniques. 27 (1);122-127.
4. Thorpe, P.H.; McLachlan, G.; Davidson-Smith, H.; Stevenson, B.J.; and Porteous, D.J. 1998. Sensitive assays to monitor the efficiency of delivery and expression of gene therapy vectors for cystic fibrosis. Pediatric Pulmonology S17; (253) p.271.
3. Thorpe, P.H. Ternent, D. and Murray, N.E. 1997. The Specificity of StySKI, a type I restriction enzyme, implies a structure with rotational symmetry. Nucleic Acids Research. 25. 1694-1700.
2. Dryden, D.T.F. Cooper, L.P. Thorpe, P.H. and Byron, O. 1997. The in vitro assembly of the EcoKI type I DNA restriction/modification enzyme and its in vivo implications. Biochemistry 36. 1065-1076.
1. Thorpe, P.H. 1995. Ph.D Thesis. Institute of Cell and Molecular Biology, Edinburgh University, UK. The DNA Specificity of Type I Restriction and Modification Enzymes.



Biography

I completed a PhD with Noreen Murray at the Institute for Cell and Molecular Biology (now ICB) at Edinburgh University looking at the DNA specificity of restriction and modification systems of bacteria. This work exploited the powerful genetics of lambda and E. coli to determine DNA specificities of novel restriction enzymes and illuminate the mechanisms of evolution and adaptation for these enzymes.

Subsequently I moved to the MRC Human Genetics Unit (and later Medical Genetics Section, Edinburgh University) with David Porteous studying gene therapy for Cystic Fibrosis (CF). My project involved designing and developing new assays that sensitively measure gene therapy in clinical trials. From 1999-2002 I pursued a CF-trust award to explore the possibility of using DNA repair as a therapy for Cystic Fibrosis. This project was focused upon manipulating the mechanisms of DNA repair (and more specifically homologous recombination) in mammalian cells. This work became part of the UK CF gene therapy consortium.

In 2002 I moved to the Department of Genetics & Development at Columbia University (New York) to work with Rodney Rothstein's group on the mechanisms of homologous recombination. Our work focuses upon the genes and proteins that are responsible for this process and their role in determining the recombination status of different cells. Recently, we have focused our attention on stem cells. A long term goal of this work is to efficiently manipulate the genome of patient-matched stem cells (such as IPS cells) to correct mutations responsible for diseases such as CF. We believe that the asymmetric division of adult stem cells provides both a means to identify them but also a potential barrier to genetic recombination.



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Disclaimer: The information provided on these pages is not guaranteed to be accurate, I would appreciate if you would e-mail me with any errors you find. Any views expressed are entirely my own and do not necessarily reflect those of my employers or other Columbia University staff/students. Last Updated June 09.