Research

Carolyn Price

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  • Carolyn Price, PhD
  • Professor
  • Academic Office:
    Department of Cancer Biology
    3125 Eden Avenue
    ML 0521
    Cincinnati, OH 45267
  • Phone: 513 558-0450
  • Email: carolyn.price@uc.edu

    Research/Clinical Interests:

  • Dr. Price studies the structure and function of telomeres, the DNA-protein complexes that cap the ends of chromosomes. Telomeres are essential for genome stability as defects in their structure and/or failure to fully replicate the telomeric DNA leads to chromosome shortening and end-to-end fusion of chromosomes. Telomere shortening due to mutations in the telomere maintenance enzyme, telomerase, limits stem cell proliferation and causes the heritable syndrome dyskeratosis congenita, while up-regulation of telomerase is a key step in tumor development because telomere elongation allows cells to proliferate indefinitely. Dr. Price and her colleagues are using genetic and biochemical approaches to examine the function of proteins that form the protective telomeric DNA-protein cap and/or ensure that the telomeric DNA is fully replicated. Her goal is to understand how telomere proteins, telomerase and DNA damage response factors cooperate to during telomere replication to allow reassembly of the of protective protein cap structure. This information is needed to understand how telomeres prevent genome instability. Her most recent and exciting discovery is a new mammalian telomere/DNA replication repair complex called CST (CTC1/STN1/TEN1). Her results indicate that CST has a separate function from Shelterin, the well characterized telomere protection complex. CST acts during several key steps in telomere replication both prior to and after telomerase action. Dr Price has discovered that CST also has genome-wide roles in recovery from replication stress. CST helps replication resume after replication fork stalling and the level of CST expression determines how well cells can tolerate various forms of DNA damage. Mutations in CST have recently been shown to cause dyskeratosis congenita and Coats plus syndrome. The severity of the patients symptoms are likely to result from the combined telomeric and genome-wide effects of CST mutation. Dr. Price is using a human somatic cell knockout system to determine the mechanism by which the CST mutations cause disease.
     

    Education/Credentials:

  • Bachelor's Degree: St Andrews University, 1977
  • Doctoral Degree: University of Colorado Medical Center, 1985

Peer Reviewed Publications (in chronological order):

  • Wang, F., Stewart, J., & Price, C. M. (2014). Human CST abundance determines recovery from diverse forms of DNA damage and replication stress. . Cell Cycle (Georgetown, Tex.) , 13 (22) , 3488-3498.
  • Kasbek, C., Wang, F., & Price, C. M. (2013). Human TEN1 maintains telomere integrity and functions in genome-wide replication restart. . The Journal of Biological Chemistry , 288 (42) , 30139-50.
  • Wang, F., Stewart, J. A., Kasbek, C., Zhao, Y., Wright, W. E., & Price, C. M. (2012). Human CST has independent functions during telomere duplex replication and C-strand fill-in. . Cell Reports , 2 (5) , 1096-103.
  • Stewart, J. A., Wang, F., Chaiken, M. F., Kasbek, C., Chastain, P. D., Wright, W. E., & Price, C. M. (2012). Human CST promotes telomere duplex replication and general replication restart after fork stalling. . The EMBO Journal , 31 (17) , 3537-49.
  • Stewart, J. A., Chaiken, M. F., Wang, F., & Price, C. M. (2012). Maintaining the end: roles of telomere proteins in end-protection, telomere replication and length regulation. . Mutation Research , 730 (1-2) , 12-9.
  • Price, Carolyn M (2012). Telomere flip-flop: an unfolding passage to senescence. . EMBO Reports , 13 (1) , 5-6.
  • Linger, B. R., Morin, G. B., & Price, C. M. (2011). The Pot1a-associated proteins Tpt1 and Pat1 coordinate telomere protection and length regulation in Tetrahymena. . Molecular Biology of the Cell , 22 (21) , 4161-70.
  • Price, Christine M (2011). Beacons of change: focusing on the future. . Journal of Perianesthesia Nursing : Official Journal of the American Society of PeriAnesthesia Nurses / American Society of PeriAnesthesia Nurses , 26 (2) , 69-71.
  • Price, C. M., Boltz, K. A., Chaiken, M. F., Stewart, J. A., Beilstein, M. A., & Shippen, D. E. (2010). Evolution of CST function in telomere maintenance. . Cell Cycle (Georgetown, Tex.) , 9 (16) , 3157-65.
  • Surovtseva, Y. V., Churikov, D., Boltz, K. A., Song, X., Lamb, J. C., Warrington, R., Leehy, K., Heacock, M., Price, C. M., & Shippen, D. E. (2009). (In Press). Conserved telomere maintenance component 1 interacts with STN1 and maintains chromosome ends in higher eukaryotes. . Molecular Cell , 36 (2) , 207-18.
  • Price, Carolyn M (2009). (In Press). Antics at the telomere: uncoupled polymerases solve the end replication problem. . The EMBO Journal , 28 (7) , 795-6.
  • Churikov, D., & Price, C. M. (2008). (In Press). Pot1 and cell cycle progression cooperate in telomere length regulation. . Nature Structural & Molecular Biology , 15 (1) , 79-84.
  • Price, Carolyn M (2007). (In Press). wRAPing up the end to prevent telomere fusions. . Molecular Cell , 26 (4) , 463-4.
  • Jacob, N. K., Lescasse, R., Linger, B. R., & Price, C. M. (2007). (In Press). Tetrahymena POT1a regulates telomere length and prevents activation of a cell cycle checkpoint. . Molecular and Cellular Biology , 27 (5) , 1592-601.
  • Churikov, D., Wei, C., & Price, C. M. (2006). (In Press). Vertebrate POT1 restricts G-overhang length and prevents activation of a telomeric DNA damage checkpoint but is dispensable for overhang protection. . Molecular and Cellular Biology , 26 (18) , 6971-82.
  • Price, Carolyn M (2006). (In Press). Stirring the POT1: surprises in telomere protection. . Nature Structural & Molecular Biology , 13 (8) , 673-4.
  • De Rycker, M., & Price, C. M. (2004). (In Press). Tankyrase polymerization is controlled by its sterile alpha motif and poly(ADP-ribose) polymerase domains. . Molecular and Cellular Biology , 24 (22) , 9802-12.
  • Jacob, N. K., Stout, A. R., & Price, C. M. (2004). (In Press). Modulation of telomere length dynamics by the subtelomeric region of tetrahymena telomeres. . Molecular Biology of the Cell , 15 (8) , 3719-28.
  • Wei, C., & Price, C. M. (2004). (In Press). Cell cycle localization, dimerization, and binding domain architecture of the telomere protein cPot1. . Molecular and Cellular Biology , 24 (5) , 2091-102.
  • Tan, M., Wei, C., & Price, C. M. (2003). (In Press). The telomeric protein Rap1 is conserved in vertebrates and is expressed from a bidirectional promoter positioned between the Rap1 and KARS genes. . Gene , 323 , 1-10.
  • De Rycker, M., Venkatesan, R. N., Wei, C., & Price, C. M. (2003). (In Press). Vertebrate tankyrase domain structure and sterile alpha motif (SAM)-mediated multimerization. . The Biochemical Journal , 372 (Pt 1) , 87-96.
  • Jacob, N. K., Kirk, K. E., & Price, C. M. (2003). (In Press). Generation of telomeric G strand overhangs involves both G and C strand cleavage. . Molecular Cell , 11 (4) , 1021-32.
  • Tan, M., Jahn, C. L., & Price, C. M. (2003). (In Press). Origin usage during euplotes ribosomal DNA amplification. . Eukaryotic Cell , 2 (1) , 115-22.
  • Ray, S., Karamysheva, Z., Wang, L., Shippen, D. E., & Price, C. M. (2002). (In Press). Interactions between telomerase and primase physically link the telomere and chromosome replication machinery. . Molecular and Cellular Biology , 22 (16) , 5859-68.
  • Wei, C., Skopp, R., Takata, M., Takeda, S., & Price, C. M. (2002). (In Press). Effects of double-strand break repair proteins on vertebrate telomere structure. . Nucleic Acids Research , 30 (13) , 2862-70.
  • Jacob, N. K., Skopp, R., & Price, C. M. (2001). (In Press). G-overhang dynamics at Tetrahymena telomeres. . The EMBO Journal , 20 (15) , 4299-308.
  • Ray, S., Jahn, C., Tebeau, C. M., Larson, M. N., & Price, C. M. (1999). (In Press). Differential expression of linker histone variants in Euplotes crassus. . Gene , 231 (1-2) , 15-20.
  • Price, C M (1999). (In Press). Telomeres and telomerase: broad effects on cell growth. . Current Opinion in Genetics & Development , 9 (2) , 218-24.
  • Klobutcher, L. A., Gygax, S. E., Podoloff, J. D., Vermeesch, J. R., Price, C. M., Tebeau, C. M., & Jahn, C. L. (1998). (In Press). Conserved DNA sequences adjacent to chromosome fragmentation and telomere addition sites in Euplotes crassus. . Nucleic Acids Research , 26 (18) , 4230-40.
  • Carlson, D. L., Skopp, R., & Price, C. M. (1997). (In Press). DNA-Binding properties of the replication telomere protein. . Biochemistry , 36 (50) , 15900-8.
  • Price, C M (1997). (In Press). Synthesis of the telomeric C-strand. A review. . Biochemistry. Biokhimii?a , 62 (11) , 1216-23.
  • Fan, X., & Price, C. M. (1997). (In Press). Coordinate regulation of G- and C strand length during new telomere synthesis. . Molecular Biology of the Cell , 8 (11) , 2145-55.
  • Shippen, D. E., Blackburn, E. H., & Price, C. M. (1994). (In Press). DNA bound by the Oxytricha telomere protein is accessible to telomerase and other DNA polymerases. . Proceedings of the National Academy of Sciences of the United States of America , 91 (1) , 405-9.
  • Vermeesch, J. R., & Price, C. M. (1994). (In Press). Telomeric DNA sequence and structure following de novo telomere synthesis in Euplotes crassus. . Molecular and Cellular Biology , 14 (1) , 554-66.
  • Vermeesch, J. R., Williams, D., & Price, C. M. (1993). (In Press). Telomere processing in Euplotes. . Nucleic Acids Research , 21 (23) , 5366-71.
  • Price, C M (1993). (In Press). Telomere structure and function. . Indian Journal of Biochemistry & Biophysics , 30 (2) , 77-82.
  • Price, C. M., Skopp, R., Krueger, J., & Williams, D. (1992). (In Press). DNA recognition and binding by the Euplotes telomere protein. . Biochemistry , 31 (44) , 10835-43.
  • Thomas, L. L., & Price, C. M. (1992). (In Press). Cellular uptake, distribution, and degradation of phosphorothioate oligonucleotides in Euplotes crassus. . Annals of the New York Academy of Sciences , 660 , 328-30.
  • Thomas, L. L., & Price, C. M. (1992). (In Press). Cellular uptake and degradation of phosphorothioate oligonucleotides by marine and freshwater ciliates. . Antisense Research and Development , 2 (3) , 251-6.
  • Price, C M (1992). (In Press). Centromeres and telomeres. . Current Opinion in Cell Biology , 4 (3) , 379-84.
  • Gray, J. T., Celander, D. W., Price, C. M., & Cech, T. R. (1991). (In Press). Cloning and expression of genes for the Oxytricha telomere-binding protein: specific subunit interactions in the telomeric complex. . Cell , 67 (4) , 807-14.
  • Price, C M (1990). (In Press). Telomere structure in Euplotes crassus: characterization of DNA-protein interactions and isolation of a telomere-binding protein. . Molecular and Cellular Biology , 10 (7) , 3421-31.
  • Hicke, B. J., Celander, D. W., MacDonald, G. H., Price, C. M., & Cech, T. R. (1990). (In Press). Two versions of the gene encoding the 41-kilodalton subunit of the telomere binding protein of Oxytricha nova. . Proceedings of the National Academy of Sciences of the United States of America , 87 (4) , 1481-5.
  • Price, C. M., & Cech, T. R. (1989). (In Press). Properties of the telomeric DNA-binding protein from Oxytricha nova. . Biochemistry , 28 (2) , 769-74.
  • Price, C. M., & Cech, T. R. (1987). (In Press). Telomeric DNA-protein interactions of Oxytricha macronuclear DNA. . Genes & Development , 1 (8) , 783-93.
  • Price, C. M., & Pettijohn, D. E. (1986). (In Press). Redistribution of the nuclear mitotic apparatus protein (NuMA) during mitosis and nuclear assembly. Properties of purified NuMA protein. . Experimental Cell Research , 166 (2) , 295-311.
  • Price, C. M., McCarty, G. A., & Pettijohn, D. E. (1984). (In Press). NuMA protein is a human autoantigen. . Arthritis and Rheumatism , 27 (7) , 774-9.
  • Linger, B. R., & Price, C. M. (In Press). Conservation of telomere protein complexes: shuffling through evolution. . Critical Reviews in Biochemistry and Molecular Biology , 44 (6) , 434-46.
  • Price, C. M., Adams, A. K., & Vermeesch, J. R. (In Press). Accumulation of telomerase RNA and telomere protein transcripts during telomere synthesis in Euplotes. . The Journal of Eukaryotic Microbiology , 41 (3) , 267-75.

    Research Grants:

  • R01 GM073169 National Institute of General Medical Sciences. Function and Regulation of Two Novel PARPs, Tankyrase 1&2, PI, Closed.
  • R01-GM-41803 National Institute of General Medical Sciences. Mechanisms of Telomere Replication, PI, Closed.
  • 5-R01-AG-17212-05-A0-S0-E0 National Institute on Aging. Identity and Function of Vertebrate Telomere Proteins, PI, Closed.
  • 5-R01-GM-41803-13-A0-S0-E0 National Institute of General Medical Sciences. Mechanisms of Telomere Replication, PI, Closed.
  • R01 GM041803 National Institute of General Medical Sciences. Mechanisms of Telomere Replication, PI, Active.
  • R01 GM088728 National Institute of General Medical Sciences. Telomere Protein Function in Tetrahymena, PI, Active.
  • F32 GM097833 National Institute of General Medical Sciences. Roles of CST, a Novel Telomere Associated Complex at the DNA Replication Fork, Collaborator, Closed.
  • R13CA168317 National Cancer Institute. 14th Annual Midwest DNA Repair Symposium, PI, Closed.
  • T32CA117846 National Cancer Institute. Training Program in Cancer Therapeutics, Collaborator, Active.
  • GM041803 National Institute of General Medical Sciences. Mechanisms of Telomere Replication, PI, Active.

Recent Awards/Honors:

  • Awards and Honors. 1985-1988 Damon Runyon-Walter Winchell Cancer Fund Postdoctoral Research Fellowship 1989-1992 March of Dimes Basil O'Connor Starter Scholar Research Award 1991-1994 American Cancer Society Junior Faculty Research Award 1997 Chromosoma Prize for the outstanding paper of the year 1997-1998 NIH Senior Fellowship 1998-1999 NSF Career Advancement Award 2009-present Graduate Faculty Fellow, University of Cincinnati