Carolyn Price

Carolyn M. Price

Professor

Vontz Center

2320

COM Can Bio Price Lab - 0521

Department of Cancer Biology
3125 Eden Avenue
Cincinnati, Ohio 45267

Professional Summary

I have been heavily involved in training students and postdoctoral fellows for over 25 years. I started mentoring undergraduates while a postdoctoral fellow and since then I have trained numerous undergraduate students, graduate students and postdoctoral fellows in my lab. I also participate in training and mentoring through our graduate program, the NIEHS Environmental Carcinogenesis and Mutagenesis training grant and as Co-PI on our NCI-funded T32 training grant in Cancer Therapeutics. I enjoy the process of mentoring and teaching and I find it gratifying to see students develop into competent young scientists and postdoctoral fellows develop the additional skills needed to have an independent research career. I have found it particularly pleasing that a large fraction of the people who have come through my lab have gone on to research careers. Many of the undergraduates have entered graduate school. All six of my PhD students went on to postdoctoral positions and then remained engaged in research. Two hold/held faculty positions, three went to industry and two then became team leaders in pharmaceutical or biotech companies. Most of my postdoctoral trainees have also continued in research either in academia or industry. A total of eight postdocs have obtained academic appointments at universities across the USA including UT Southwestern, Ohio State, Creighton Univ., Univ. Nebraska, Omaha and two more will take up tenure track assistant professor positions this summer.
My lab-based training of students and postdocs has been in the context of my studies of telomere structure and replication in ciliated protozoa and human cells. Over the years, our work with ciliates has revealed a number of new paradigms that were later shown to hold true in yeast and mammals. I initiated our vertebrate telomere project using chicken DT40 cells because the efficient gene-targeting facilitated generation of conditional cell lines. We used the DT40 system to study how telomere proteins prevent the chromosome terminus from activating DNA damage checkpoints. Most recently, our focus has been on the role of CST (CTC1/STN1/TEN1). My lab co-discovered human CTC1 and showed that it is important for genomic stability and telomere structure. Our recent studies indicate that CST plays key roles in telomere replication as it facilitates replication of the telomere duplex and is needed for C-strand fill-in after telomerase action on the DNA terminus. Our work also indicates that CST functions in genome-wide replication restart after replication fork stalling at sites of DNA damage. Recently we have shown that the level of CST expression determines how well cells can tolerate various forms of DNA damage including UV-induced thymidine dimers. Thus, CST appears to provide a previously unrecognized pathway for cells to survive environmental insult.  

Education

Bachelor's Degree, St Andrews University 1977 (Biochemistry)

Doctoral Degree, University of Colorado Medical Center 1985 (Biochemistry)

Positions and Work Experience

1988 -1994 Assistant Professor , Department of Chemistry, University of Nebraska, Lincoln, Nebraska

1994 -2000 Associate Professor, Departments of Chemistry and Biochemistry, University of Nebraska, Lincoln, Nebraska

2000 -2006 Associate Professor, Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH

2006 -2008 Professor, Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati, Cincinnati, OH

2008 -To Present Professor, Department of Cancer Biology, University of Cincinnati, Cincinnati, OH

Research and Practice 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.
 

Research Support

Grant: #R01 GM073169 Investigators:Price, Carolyn 08-01-2005 -07-31-2010 National Institute of General Medical Sciences Function and Regulation of Two Novel PARPs, Tankyrase 1&2 Role:PI $1,025,519.00 Closed Level:Federal

Grant: #R01-GM-41803 Investigators:Price, Carolyn 12-01-2003 -07-31-2008 National Institute of General Medical Sciences Mechanisms of Telomere Replication Role:PI $1,235,001.00 Closed Level:Federal

Grant: #5-R01-AG-17212-05-A0-S0-E0 Investigators:Price, Carolyn 09-01-2000 -06-30-2004 National Institute on Aging Identity and Function of Vertebrate Telomere Proteins Role:PI $861,003.00 Closed Level:Federal

Grant: #5-R01-GM-41803-13-A0-S0-E0 Investigators:Price, Carolyn 12-01-2000 -11-30-2003 National Institute of General Medical Sciences Mechanisms of Telomere Replication Role:PI $571,406.00 Closed Level:Federal

Grant: #R01 GM041803 Investigators:Price, Carolyn 07-01-2008 -07-31-2013 National Institute of General Medical Sciences Mechanisms of Telomere Replication Role:PI $1,305,677.00 Active Level:Federal

Grant: #R01 GM088728 Investigators:Price, Carolyn 08-01-2009 -06-30-2014 National Institute of General Medical Sciences Telomere Protein Function in Tetrahymena Role:PI $1,240,362.00 Active Level:Federal

Grant: #F32 GM097833 Investigators:Price, Carolyn; Stewart, Jason 04-18-2011 -07-31-2012 National Institute of General Medical Sciences Roles of CST, a Novel Telomere Associated Complex at the DNA Replication Fork Role:Collaborator $68,509.00 Closed Level:Federal

Grant: #R13CA168317 Investigators:Price, Carolyn 04-01-2012 -03-31-2013 National Cancer Institute 14th Annual Midwest DNA Repair Symposium Role:PI $6,000.00 Closed Level:Federal

Grant: #T32CA117846 Investigators:Price, Carolyn; Waltz, Susan 09-14-2012 -08-31-2017 National Cancer Institute Training Program in Cancer Therapeutics Role:Collaborator $742,942.00 Active Level:Federal

Grant: #GM041803 Investigators:Price, Carolyn 08-01-2013 -07-31-2017 National Institute of General Medical Sciences Mechanisms of Telomere Replication Role:PI $338,794.00 Active Level:Federal

Grant: #T32CA117846 Investigators:Price, Carolyn; Waltz, Susan 09-01-2018 -08-31-2023 National Cancer Institute Pathways to Cancer Therapeutics Role:Collaborator $459,588.00 Active Level:Federal

Publications

Peer Reviewed Publications

Linger, Benjamin R; Price, Carolyn M Conservation of telomere protein complexes: shuffling through evolution.Critical reviews in biochemistry and molecular biology, ,44 (6 ),434-46

Surovtseva, Yulia V; Churikov, Dmitri; Boltz, Kara A; Song, Xiangyu; Lamb, Jonathan C; Warrington, Ross; Leehy, Katherine; Heacock, Michelle; Price, Carolyn M; Shippen, Dorothy E (2009. )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. )Antics at the telomere: uncoupled polymerases solve the end replication problem.The EMBO journal, ,28 (7 ),795-6

Churikov, Dmitri; Price, Carolyn M (2008. )Pot1 and cell cycle progression cooperate in telomere length regulation.Nature structural & molecular biology, ,15 (1 ),79-84

Price, Carolyn M (2007. )wRAPing up the end to prevent telomere fusions.Molecular cell, ,26 (4 ),463-4

Jacob, Naduparambil K; Lescasse, Rachel; Linger, Benjamin R; Price, Carolyn M (2007. )Tetrahymena POT1a regulates telomere length and prevents activation of a cell cycle checkpoint.Molecular and cellular biology, ,27 (5 ),1592-601

Churikov, Dmitri; Wei, Chao; Price, Carolyn M (2006. )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. )Stirring the POT1: surprises in telomere protection.Nature structural & molecular biology, ,13 (8 ),673-4

De Rycker, Manu; Price, Carolyn M (2004. )Tankyrase polymerization is controlled by its sterile alpha motif and poly(ADP-ribose) polymerase domains.Molecular and cellular biology, ,24 (22 ),9802-12

Jacob, Naduparambil K; Stout, Angela R; Price, Carolyn M (2004. )Modulation of telomere length dynamics by the subtelomeric region of tetrahymena telomeres.Molecular biology of the cell, ,15 (8 ),3719-28

Wei, Chao; Price, Carolyn M (2004. )Cell cycle localization, dimerization, and binding domain architecture of the telomere protein cPot1. Molecular and cellular biology, ,24 (5 ),2091-102

Tan, Ming; Wei, Chao; Price, Carolyn M (2003. )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, Manu; Venkatesan, Ranga N; Wei, Chao; Price, Carolyn M (2003. )Vertebrate tankyrase domain structure and sterile alpha motif (SAM)-mediated multimerization.The Biochemical journal, ,372 (Pt 1 ),87-96

Jacob, Naduparambil K; Kirk, Karen E; Price, Carolyn M (2003. )Generation of telomeric G strand overhangs involves both G and C strand cleavage. Molecular cell, ,11 (4 ),1021-32

Tan, Ming; Jahn, Carolyn L; Price, Carolyn M (2003. )Origin usage during euplotes ribosomal DNA amplification. Eukaryotic cell, ,2 (1 ),115-22

Ray, Saugata; Karamysheva, Zemfira; Wang, Libin; Shippen, Dorothy E; Price, Carolyn M (2002. )Interactions between telomerase and primase physically link the telomere and chromosome replication machinery. Molecular and cellular biology, ,22 (16 ),5859-68

Wei, Chao; Skopp, Rose; Takata, Minoru; Takeda, Shunichi; Price, Carolyn M (2002. )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. )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. )Differential expression of linker histone variants in Euplotes crassus. Gene, ,231 (1-2 ),15-20

Price, C M (1999. )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. )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. )DNA-Binding properties of the replication telomere protein.Biochemistry, ,36 (50 ),15900-8

Price, C M (1997. )Synthesis of the telomeric C-strand. A review. Biochemistry. Biokhimii?a, ,62 (11 ),1216-23

Fan, X; Price, C M (1997. )Coordinate regulation of G- and C strand length during new telomere synthesis. Molecular biology of the cell, ,8 (11 ),2145-55

Price, C M; Adams, A K; Vermeesch, J R Accumulation of telomerase RNA and telomere protein transcripts during telomere synthesis in Euplotes. The Journal of eukaryotic microbiology, ,41 (3 ),267-75

Shippen, D E; Blackburn, E H; Price, C M (1994. )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. )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. )Telomere processing in Euplotes. Nucleic acids research, ,21 (23 ),5366-71

Price, C M (1993. )Telomere structure and function. Indian journal of biochemistry & biophysics, ,30 (2 ),77-82

Price, C M; Skopp, R; Krueger, J; Williams, D (1992. )DNA recognition and binding by the Euplotes telomere protein. Biochemistry, ,31 (44 ),10835-43

Thomas, L L; Price, C M (1992. )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. )Cellular uptake and degradation of phosphorothioate oligonucleotides by marine and freshwater ciliates. Antisense research and development, ,2 (3 ),251-6

Price, C M (1992. )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. )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. )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. )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. )Properties of the telomeric DNA-binding protein from Oxytricha nova. Biochemistry, ,28 (2 ),769-74

Price, C M; Cech, T R (1987. )Telomeric DNA-protein interactions of Oxytricha macronuclear DNA. Genes & development, ,1 (8 ),783-93

Price, C M; Pettijohn, D E (1986. )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. )NuMA protein is a human autoantigen. Arthritis and rheumatism, ,27 (7 ),774-9

Kasbek, Christopher; Wang, Feng; Price, Carolyn M (2013. )Human TEN1 maintains telomere integrity and functions in genome-wide replication restart.The Journal of biological chemistry, ,288 (42 ),30139-50

Wang, Feng; Stewart, Jason A; Kasbek, Christopher; Zhao, Yong; Wright, Woodring E; Price, Carolyn M (2012. )Human CST has independent functions during telomere duplex replication and C-strand fill-in.Cell reports, ,2 (5 ),1096-103

Stewart, Jason A; Wang, Feng; Chaiken, Mary F; Kasbek, Christopher; Chastain, Paul D; Wright, Woodring E; Price, Carolyn M (2012. )Human CST promotes telomere duplex replication and general replication restart after fork stalling.The EMBO journal, ,31 (17 ),3537-49

Stewart, Jason A; Chaiken, Mary F; Wang, Feng; Price, Carolyn 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, Benjamin R; Morin, Gregg B; Price, Carolyn 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, Carolyn M; Boltz, Kara A; Chaiken, Mary F; Stewart, Jason A; Beilstein, Mark A; Shippen, Dorothy E (2010. )Evolution of CST function in telomere maintenance.Cell cycle (Georgetown, Tex.), ,9 (16 ),3157-65

Wang, Feng; Stewart, Jason; Price, Carolyn M (2014. )Human CST abundance determines recovery from diverse forms of DNA damage and replication stress.Cell cycle (Georgetown, Tex.), ,13 (22 ),3488-3498

Feng, Xuyang; Hsu, Shih-Jui; Kasbek, Christopher; Chaiken, Mary; Price, Carolyn M (2017. )CTC1-mediated C-strand fill-in is an essential step in telomere length maintenance.Nucleic acids research, ,45 (8 ),4281-4293

Bhattacharjee, Anukana; Stewart, Jason; Chaiken, Mary; Price, Carolyn M (2016. )STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function.PLoS genetics, ,12 (9 ),e1006342

Cranert, S, Heyse, S, Linger, BR, Lescasse, R, Price, CM (2014. )Tetrahymena Pot2 is a developmentally regulated paralog of Pot1 that localizes to chromosome breakage sites but not to telomeres.Eukaryot. Cell, ,13 ,1519-1529

Premkumar VL, Cranert S, Linger BR, Morin GB, Minium S, Price, CM (2014. )The 3’ overhangs at Tetrahymena telomeres are packaged by four proteins: Pot1a, Tpt1, Pat1 and Pat2.Eukaryot. Cell, ,13 (2 ),240-245

Bhattacharjee, Anukana; Wang, Yongyao; Diao, Jiajie; Price, Carolyn M (2017. )Dynamic DNA binding, junction recognition and G4 melting activity underlie the telomeric and genome-wide roles of human CST.Nucleic acids research, ,45 (21 ),12311-12324

Adams, Shannel R; Maezawa, So; Alavattam, Kris G; Abe, Hironori; Sakashita, Akihiko; Shroder, Megan; Broering, Tyler J; Sroga Rios, Julie; Thomas, Michael A; Lin, Xinhua; Price, Carolyn M; Barski, Artem; Andreassen, Paul R; Namekawa, Satoshi H (2018. )RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for escape gene activation on the sex chromosomes.PLoS genetics, ,14 (2 ),e1007233

Feng, Xuyang; Hsu, Shih-Jui; Bhattacharjee, Anukana; Wang, Yongyao; Diao, Jiajie; Price, Carolyn M (2018. )CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells.Nature communications, ,9 (1 ),2827

Zhang, Miaomiao; Wang, Bing; Li, Tingfang; Liu, Rui; Xiao, Yingnan; Geng, Xin; Li, Guang; Liu, Qiang; Price, Carolyn M; Liu, Yang; Wang, Feng (2019. )Mammalian CST averts replication failure by preventing G-quadruplex accumulation.Nucleic acids research, ,

Honors and Awards

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

Post Graduate Training and Education

1985-1988 Postdoctoral fellow, Telomere biology Thomas Cech Mentor, University of Colorado at Boulder, ,Boulder, Colorado

Keywords

Telomere Telomerase DNA replication DNA repair Chromosome

Professional Affiliation

Professional Service and Experience 1993-1996 Editorial board for Chromosome Research 1994-1998 Editorial board for Journal of Eukaryotic Microbiology 1994-present Reviewer for the National Science Foundation. Also provide periodic reviews for the Israeli Sci. Found., Israeli Cancer Res. Fund., Cancer Res. UK, German Sci. Found., Italian Assoc. for Cancer Res., Human Frontiers Res. Prog., Wellcome Trust. 1997 Co-chair of FASEB conference on Ciliate Molecular Biology 1999 Co-chair NIH workshop on Chromatin, Transcription and DNA replication 1996-2000 Member of NIH Molecular Cytology study section 2003-20010 Ad hoc reviewer for NIH Cell Development and Function (CDF1), Radiation Therapeutics and Biology (RTB), Developmental Therapeutics (DT), Molecular Genetics A (MGA), Nuclear Development and Transport (NDT), Molecular Genetics c (MGC) and ZRG1 BDA-M 02 study sections 2007 Chair of FASEB conference on Ciliate Molecular Biology

Contact Information

Academic - Department of Cancer Biology
3125 Eden Avenue
Cincinnati  Ohio, 45267
Phone: 513 558-0450
carolyn.price@uc.edu