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Carol W. Greider

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Carolyn Widney Greider (born April 15, 1961) is an American molecular biologist and Nobel laureate. She is a Distinguished Professor of Molecular, Cell, and Developmental Biology[1] at the University of California, Santa Cruz.

Carol W. Greider
Greider in 2021
Born
Carolyn Widney Greider

(1961-04-15) April 15, 1961 (age 63)
San Diego, California, U.S.
EducationUniversity of California, Santa Barbara (BA)
University of Göttingen
University of California, Berkeley (PhD)
Known forDiscovery of telomerase
Spouse
​
​
(m. 1993; div. 2011)​
Children2
AwardsRichard Lounsbery Award (2003)
Lasker Award (2006)
Louisa Gross Horwitz Prize (2007)
Nobel Prize in Physiology or Medicine (2009)
Scientific career
FieldsMolecular biology
InstitutionsCold Spring Harbor Laboratory
Johns Hopkins School of Medicine
University of California, Santa Cruz
ThesisIdentification of a specific telomere terminal transferase activity in Tetrahymena extracts (1985)
Doctoral advisorElizabeth Blackburn
Other academic advisorsBeatrice M. Sweeney
David J. Asai
Leslie Wilson

Greider discovered the enzyme telomerase in 1984, while she was a graduate student of Elizabeth Blackburn at the University of California, Berkeley. Greider pioneered research on the structure of telomeres, the ends of the chromosomes. She was awarded the 2009 Nobel Prize for Physiology or Medicine, along with Blackburn and Jack W. Szostak, for their discovery that telomeres are protected from progressive shortening by the enzyme telomerase.[2]

Early life and education

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Greider was born in San Diego, California.[3] Her father, Kenneth Greider, was a physics professor.[4] Her family moved from San Diego to Davis, California, where she spent many of her early years and graduated from Davis Senior High School in 1979. She graduated from the College of Creative Studies at the University of California, Santa Barbara, with a B.A. in biology in 1983. During this time she also studied at the University of Göttingen and made significant discoveries there.[5]

Greider is dyslexic and states that her "compensatory skills also played a role in my success as a scientist because one has to intuit many different things that are going on at the same time and apply those to a particular problem".[6] Greider initially suspected her dyslexia after seeing patterns of common mistakes such as backward words when she received back graded work in the first grade.[7] Greider started to memorize words and their spellings rather than attempting to sound out the spelling of words.[6] Greider has worked significantly to overcome her dyslexia to become successful in her professional life and credits her dyslexia as helping her appreciate differences and making unusual decisions such as the one to work with Tetrahymena, an unusual organism.[6]

Greider initially had difficulty getting into graduate school because of her low GRE scores due to her dyslexia. Greider applied to thirteen grad schools and was accepted to only two, California Institute of Technology and the University of California, Berkeley.[6] She chose to study at Berkeley.[6]

Discovery of telomerase

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Greider completed her Ph.D. in molecular biology in 1987 at Berkeley under Elizabeth Blackburn. While at Berkeley, Greider and Blackburn discovered how chromosomes are protected by telomeres and the enzyme telomerase.[8] Greider joined Blackburn's laboratory in April 1984 looking for the enzyme that was hypothesized to add extra DNA bases to the ends of chromosomes. Without the extra bases, which are added as repeats of a six-base pair motif, chromosomes are shortened during DNA replication, eventually resulting in chromosome deterioration and senescence or cancer-causing chromosome fusion. Blackburn and Greider looked for the enzyme in the model organism Tetrahymena thermophila, a fresh-water protozoan with a large number of telomeres.[9]

On December 25, 1984, Greider obtained results indicating that a particular enzyme was likely responsible. After six months of additional research, Greider and Blackburn concluded that it was the enzyme responsible for telomere addition. They published their findings in the journal Cell in December 1985.[10] The enzyme, originally called "telomere terminal transferase," is now known as telomerase. Telomerase rebuilds the tips of chromosomes and determines the life span of cells.[11]

Greider's additional research to confirm her discovery was largely focused on identifying the mechanism that telomerase uses for elongation.[12] Greider chose to use RNA degrading enzymes and saw that the telomeres stopped extending, which was an indication that RNA was involved in the enzyme.[12]

Subsequent career

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Greider then started her laboratory as a Cold Spring Harbor Laboratory Fellow, and also held a faculty position, at the Cold Spring Harbor Laboratory, Long Island, New York. Greider continued to study Tetrahymena telomerase, cloning the gene encoding the RNA component and demonstrating that it provided the template for the TTGGGG telomere repeats (1989)[13] as well as establishing that telomerase is processive (1991).[14] She was also able to reconstitute Tetrahymena telomerase in vitro (1994)[15] and define the mechanisms of template utilization (1995).[16] Greider also worked with Calvin Harley to show that telomere shortening underlies cellular senescence (1990).[17][18] To further test this idea mouse and human telomerase were characterized (1993)[19] (1995)[20] and the mouse telomerase RNA component was cloned (1995).[21]

During this time, Greider, in collaboration with Ronald A. DePinho, produced the first telomerase knockout mouse,[22] showing that although telomerase is dispensable for life, increasingly short telomeres result in various deleterious phenotypes, colloquially referred to as premature aging.[23] In the mid-1990s, Greider was recruited by Michael D. West, founder of biotechnology company Geron (now CEO of AgeX Therapeutics) to join the company's Scientific Advisory Board[24] and remained on the Board until 1997.

Greider accepted a faculty position at the Johns Hopkins University School of Medicine in 1997. Greider continued to study telomerase deficient mice and saw that her sixth generation of mice had become entirely sterile,[25] but when mated with control mice the telomerase deficient mice were able to regenerate their telomeres.[12][26] Greider continued to work on telomerase biochemistry, defining the secondary structure (2000) [27] and template boundary (2003)[28] of vertebrate telomerase RNA as well as analyzing the pseudoknot structure in human telomerase RNA (2005).[29] In addition to working in Tetrahymena and mammalian systems, Greider also studied telomeres and telomerase in the yeast Saccharomyces cerevisiae, further characterizing the recombination-based gene conversion mechanism that yeast cells null for telomerase use to maintain telomeres (1999)[30] (2001).[31] Greider also showed that short telomeres elicit a DNA damage response in yeast (2003).[32]

Greider, Blackburn, and Szostak shared the 2006 Albert Lasker Award for Basic Medical Research for their work on telomeres,[33] before jointly receiving the Nobel Prize in 2009.

In February 2014, Greider was named a Bloomberg Distinguished Professor at Johns Hopkins University.[34]

Greider served as director of and professor at the Department of Molecular Biology and Genetics at Johns Hopkins Medicine.[11] Greider was first promoted to Daniel Nathans Professor at the Department of Molecular Biology and Genetics in 2004.[35]

As of 2021, she is a professor of molecular, cellular, and developmental biology at UCSC.[citation needed]

Greider's lab employs both student and post-doctoral trainees[36] to further examine the relationships between the biology of telomeres and their connection to disease.[35] Greider's lab uses a variety of tools including yeast, mice, and biochemistry to look at progressive telomere shortening.[37] Greider's lab is also researching how tumor reformation can be controlled by the presence of short telomeres.[37] The lab's future work will focus more on identifying the processing and regulation of telomeres and telomere elongation.[37]

Personal life

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Greider married Nathaniel C. Comfort, a fellow academic, in 1992. They divorced in 2011. She has two children.[38]

Awards and honors

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Selected works

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  • Greider, C. W. & Blackburn, E. H. (1985). "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts". Cell. 43 (2 Pt. 1): 405–413. doi:10.1016/0092-8674(85)90170-9. PMID 3907856.
  • Greider, C. W. & Blackburn, E. H. (1996). "Telomeres, Telomerase and Cancer". Scientific American. 274 (2): 92–97. Bibcode:1996SciAm.274b..92G. doi:10.1038/scientificamerican0296-92. PMID 8560215.

See also

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References

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  1. ^ Stephens, Tim. "Eminent biologist Carol Greider to join UC Santa Cruz faculty". UC Santa Cruz News. Retrieved May 22, 2020.
  2. ^ "Blackburn, Greider, and Szostak share Nobel". Dolan DNA Learning Center. Archived from the original on October 22, 2009. Retrieved October 5, 2009.
  3. ^ Hopkins "Telomere" expert Carol Greider shares Germany's largest science prize
  4. ^ "Former Davis resident receives Nobel Prize". The California Aggie. October 12, 2009. Retrieved April 7, 2015.
  5. ^ Press release, University of Göttingen (December 9, 2009). (German)
  6. ^ a b c d e Kathy Crockett. "Carol Greider, Scientist, Nobel Prize Winner". Yale University. The Yale Center for Dyslexia & Creativity. Retrieved March 5, 2015.
  7. ^ "Carol W. Greider – Biographical". www.nobelprize.org. Retrieved September 28, 2017.
  8. ^ "The Nobel Prize in Physiology or Medicine 2009". Retrieved April 7, 2015.
  9. ^ Nuzzo, R. (2005). "Biography of Carol W. Greider". Proceedings of the National Academy of Sciences of the United States of America. 102 (23): 8077–8079. Bibcode:2005PNAS..102.8077N. doi:10.1073/pnas.0503019102. PMC 1149435. PMID 15928079.
  10. ^ Greider, C. W.; Blackburn, E. H. (1985). "Identification of a specific telomere terminal transferase activity in Tetrahymena extracts". Cell. 43 (2 Pt 1): 405–413. doi:10.1016/0092-8674(85)90170-9. PMID 3907856.
  11. ^ a b "Carol Greider, Ph.D." Johns Hopkins Medicine – Research – Awards – Nobel. Archived from the original on August 28, 2015. Retrieved April 7, 2015.
  12. ^ a b c Aicher, Toby (March 18, 2015). "Science Spotlight: Nobel Laureate Carol Greider". The Middlebury Campus. Retrieved January 24, 2020.
  13. ^ Greider, Carol W.; Blackburn, Elizabeth H. (January 1989). "A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis". Nature. 337 (6205): 331–337. Bibcode:1989Natur.337..331G. doi:10.1038/337331a0. PMID 2463488. S2CID 29191852.
  14. ^ Greider, C W (September 1991). "Telomerase is processive". Molecular and Cellular Biology. 11 (9): 4572–4580. doi:10.1128/MCB.11.9.4572. PMC 361337. PMID 1875940.
  15. ^ Autexier, C; Greider, C W (March 1, 1994). "Functional reconstitution of wild-type and mutant Tetrahymena telomerase". Genes & Development. 8 (5): 563–575. doi:10.1101/gad.8.5.563. PMID 7523243.
  16. ^ Autexier, C; Greider, C W (September 15, 1995). "Boundary elements of the Tetrahymena telomerase RNA template and alignment domains". Genes & Development. 9 (18): 2227–2239. doi:10.1101/gad.9.18.2227. PMID 7557377.
  17. ^ Greider, Carol W. (August 1990). "Telomeres, telomerase and senescence". BioEssays. 12 (8): 363–369. doi:10.1002/bies.950120803. PMID 2241933. S2CID 11920124.
  18. ^ Harley, Calvin B.; Futcher, A. Bruce; Greider, Carol W. (May 1990). "Telomeres shorten during ageing of human fibroblasts". Nature. 345 (6274): 458–460. Bibcode:1990Natur.345..458H. doi:10.1038/345458a0. PMID 2342578. S2CID 1145492.
  19. ^ Prowse, K. R.; Avilion, A. A.; Greider, C. W. (February 15, 1993). "Identification of a nonprocessive telomerase activity from mouse cells". Proceedings of the National Academy of Sciences. 90 (4): 1493–1497. Bibcode:1993PNAS...90.1493P. doi:10.1073/pnas.90.4.1493. PMC 45900. PMID 8434010.
  20. ^ Feng, J.; Funk, W.; Wang, S.; Weinrich, S.; Avilion, A.; Chiu, C.; Adams, R.; Chang, E.; Allsopp, R.; Yu, J.; al., e. (September 1, 1995). "The RNA component of human telomerase". Science. 269 (5228): 1236–1241. Bibcode:1995Sci...269.1236F. doi:10.1126/science.7544491. PMID 7544491. S2CID 9440710.
  21. ^ Blasco, M.; Funk, W.; Villeponteau, B.; Greider, C. (September 1, 1995). "Functional characterization and developmental regulation of mouse telomerase RNA". Science. 269 (5228): 1267–1270. Bibcode:1995Sci...269.1267B. doi:10.1126/science.7544492. PMID 7544492. S2CID 1315745.
  22. ^ Blasco, María A; Lee, Han-Woong; Hande, M.Prakash; Samper, Enrique; Lansdorp, Peter M; DePinho, Ronald A; Greider, Carol W (October 1997). "Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA". Cell. 91 (1): 25–34. doi:10.1016/s0092-8674(01)80006-4. PMID 9335332. S2CID 13366934.
  23. ^ Rudolph, Karl Lenhard; Chang, Sandy; Lee, Han-Woong; Blasco, Maria; Gottlieb, Geoffrey J; Greider, Carol; DePinho, Ronald A (March 1999). "Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice". Cell. 96 (5): 701–712. doi:10.1016/s0092-8674(00)80580-2. PMID 10089885. S2CID 11991355.
  24. ^ "Geron Corporation 10K 1996".
  25. ^ Lee, Han-Woong; Blasco, Maria A.; Gottlieb, Geoffrey J.; Horner, James W.; Greider, Carol W.; DePinho, Ronald A. (April 1998). "Essential role of mouse telomerase in highly proliferative organs". Nature. 392 (6676): 569–574. Bibcode:1998Natur.392..569L. doi:10.1038/33345. PMID 9560153. S2CID 4385788.
  26. ^ Hemann, Michael T; Strong, Margaret A; Hao, Ling-Yang; Greider, Carol W (October 2001). "The Shortest Telomere, Not Average Telomere Length, Is Critical for Cell Viability and Chromosome Stability". Cell. 107 (1): 67–77. doi:10.1016/s0092-8674(01)00504-9. PMID 11595186. S2CID 10719526.
  27. ^ Chen, Jiunn-Liang; Blasco, Maria A; Greider, Carol W (March 2000). "Secondary Structure of Vertebrate Telomerase RNA". Cell. 100 (5): 503–514. doi:10.1016/s0092-8674(00)80687-x. PMID 10721988. S2CID 15642776.
  28. ^ Chen, J.-L. (November 15, 2003). "Template boundary definition in mammalian telomerase". Genes & Development. 17 (22): 2747–2752. doi:10.1101/gad.1140303. PMC 280623. PMID 14630939.
  29. ^ Chen, J.-L.; Greider, C. W. (April 22, 2005). "Functional analysis of the pseudoknot structure in human telomerase RNA". Proceedings of the National Academy of Sciences. 102 (23): 8080–8085. Bibcode:2005PNAS..102.8080C. doi:10.1073/pnas.0502259102. PMC 1149427. PMID 15849264.
  30. ^ Le, S; Moore, JK; Haber, JE; Greider, CW (May 1999). "RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase". Genetics. 152 (1): 143–52. doi:10.1093/genetics/152.1.143. PMC 1460580. PMID 10224249.
  31. ^ Chen, Q.; Ijpma, A.; Greider, C. W. (March 1, 2001). "Two Survivor Pathways That Allow Growth in the Absence of Telomerase Are Generated by Distinct Telomere Recombination Events". Molecular and Cellular Biology. 21 (5): 1819–1827. doi:10.1128/MCB.21.5.1819-1827.2001. PMC 86745. PMID 11238918.
  32. ^ IJpma, Arne S.; Greider, Carol W.; Koshland, Douglas (March 2003). "Short Telomeres Induce a DNA Damage Response in". Molecular Biology of the Cell. 14 (3): 987–1001. doi:10.1091/mbc.02-04-0057. PMC 151574. PMID 12631718.
  33. ^ ""Telomere" Expert Carol Greider Shares 2009 Nobel Prize in Physiology or Medicine". Johns Hopkins University. Retrieved March 13, 2015.
  34. ^ Brooks, Kelly (February 17, 2014). "With Bloomberg Distinguished Professorships, Johns Hopkins aims to foster cross-specialty collaboration". Hub. Johns Hopkins University. Retrieved March 12, 2015.
  35. ^ a b "The Women of Hopkins". The Women of Hopkins. Retrieved October 5, 2017.
  36. ^ Paletta, Thomas M. Burton and Damian (March 2, 2013). "NIH Cuts Began Ahead of Sequester". Wall Street Journal. ISSN 0099-9660. Retrieved October 5, 2017.
  37. ^ a b c "The Greider Lab | Johns Hopkins Medicine". www.greiderlab.org. Retrieved October 6, 2017.
  38. ^ Clint Talbott. "'Having it all' plus 'doing it all'". Colorado Arts & Sciences Magazine. Archived from the original on February 20, 2015. Retrieved March 5, 2015.
  39. ^ "Carol W. Greider, Ph.D." bit.ly. Retrieved January 31, 2020.
  40. ^ "Carol Greider". Gairdner Foundation. Retrieved January 31, 2020.
  41. ^ "Past Winners". www.brandeis.edu. Retrieved January 31, 2020.
  42. ^ "Recipients of the Passano Laureate and Physician Scientist Awards". The Passano Foundation, Inc. Retrieved January 31, 2020.
  43. ^ "Carol W. Greider Biography and Interview". www.achievement.org. American Academy of Achievement. June 16, 2000.
  44. ^ "Book of Members, 1780–2010: Chapter B" (PDF). American Academy of Arts and Sciences. Retrieved June 9, 2011.
  45. ^ "Greider, Carol W." National Academy of Sciences. Retrieved June 9, 2011.
  46. ^ NAS Online Archived December 9, 2006, at the Wayback Machine ("For her pioneering biochemical and genetic studies of telomerase, the enzyme that maintains the ends of chromosomes in eukaryotic cells.")
  47. ^ "Lila and Murray Gruber Memorial Cancer Research Award and Lectureship". www.aad.org. Retrieved January 31, 2020.
  48. ^ Foundation, Lasker. "2006 Lasker Awards". The Lasker Foundation. Retrieved January 31, 2020.
  49. ^ "Wiley: The Wiley Foundation Announces Recipients of the Fifth Annual Wiley Prize in Biomedical Sciences". www.wiley.com. Retrieved January 31, 2020.
  50. ^ "Carol W. Greider, PhD | Dickson Prize in Medicine | University of Pittsburgh". www.dicksonprize.pitt.edu. Retrieved January 31, 2020.
  51. ^ "Horwitz Prize Awardees". Columbia University Irving Medical Center. June 20, 2018. Retrieved January 31, 2020.
  52. ^ "Recipients". Greengard Prize. Retrieved January 31, 2020.
  53. ^ "Nobel Prize in Physiology or Medicine 2009". Nobel Foundation. Retrieved October 5, 2009.
  54. ^ "Press Release 2008" (PDF). Retrieved January 31, 2020.
  55. ^ "IOM Class of 2010". Institute of Medicine. Archived from the original on April 22, 2011. Retrieved June 9, 2011.
  56. ^ "Carson, Hopkins Colleagues Named to Institute of Medicine". hopkinschildrens.org. October 11, 2010. Archived from the original on November 25, 2010. Retrieved October 1, 2013.
  57. ^ "APS Member History". search.amphilsoc.org. Retrieved January 31, 2020.
  58. ^ "Press Release AWIS 2019 Awards". www.awis.org. November 8, 2018.
  59. ^ "Past Recipients". Association for Molecular Pathology. Retrieved April 12, 2023.

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