Greider isdyslexic 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".[7] 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.[8] Greider started to memorize words and their spellings rather than attempting to sound out the spelling of words.[7] 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 withTetrahymena, an unusual organism.[7]
Greider completed her Ph.D. inmolecular biology in 1987 atBerkeley underElizabeth Blackburn. While at Berkeley, Greider and Blackburn discovered how chromosomes are protected bytelomeres and the enzymetelomerase.[9]Greider joined Blackburn's laboratory in April 1984 looking for the enzyme that was hypothesized to add extraDNA bases to the ends ofchromosomes. Without the extra bases, which are added as repeats of a six-base pair motif, chromosomes are shortened duringDNA replication, eventually resulting in chromosome deterioration andsenescence or cancer-causing chromosome fusion. Blackburn and Greider looked for the enzyme in the model organismTetrahymena thermophila, a fresh-waterprotozoan with a large number of telomeres.[10]
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 journalCell in December 1985.[11] 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.[12]
Greider's additional research to confirm her discovery was largely focused on identifying the mechanism that telomerase uses for elongation.[13] Greider chose to useRNA degrading enzymes and saw that the telomeres stopped extending, which was an indication that RNA was involved in the enzyme.[13]
Greider then started her laboratory as a Cold Spring Harbor Laboratory Fellow, and also held a faculty position, at theCold Spring Harbor Laboratory,Long Island, New York. Greider continued to studyTetrahymena telomerase, cloning the gene encoding the RNA component and demonstrating that it provided the template for the TTGGGG telomere repeats (1989)[14] as well as establishing that telomerase is processive (1991).[15] She was also able to reconstituteTetrahymena telomerasein vitro (1994)[16] and define the mechanisms of template utilization (1995).[17] Greider also worked with Calvin Harley to show that telomere shortening underlies cellular senescence (1990).[18][19] To further test this idea mouse and human telomerase were characterized (1993)[20] (1995)[21] and the mouse telomerase RNA component was cloned (1995).[22]
During this time, Greider, in collaboration withRonald A. DePinho, produced the first telomeraseknockout mouse,[23] showing that although telomerase is dispensable for life, increasingly short telomeres result in various deleteriousphenotypes, colloquially referred to as premature aging.[24] In the mid-1990s, Greider was recruited byMichael D. West, founder of biotechnology companyGeron (now CEO ofAgeX Therapeutics) to join the company's Scientific Advisory Board[25] and remained on the Board until 1997.
Greider accepted a faculty position at theJohns 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,[26] but when mated with control mice the telomerase deficient mice were able to regenerate theirtelomeres.[13][27] Greider continued to work on telomerase biochemistry, defining the secondary structure (2000)[28] and template boundary (2003)[29] of vertebrate telomerase RNA as well as analyzing the pseudoknot structure in human telomerase RNA (2005).[30] In addition to working inTetrahymena and mammalian systems, Greider also studied telomeres and telomerase in the yeastSaccharomyces cerevisiae, further characterizing the recombination-based gene conversion mechanism that yeast cells null for telomerase use to maintain telomeres (1999)[31] (2001).[32] Greider also showed that short telomeres elicit a DNA damage response in yeast (2003).[33]
Greider served as director of and professor at the Department of Molecular Biology and Genetics atJohns Hopkins Medicine.[12] Greider was first promoted to Daniel Nathans Professor at the Department of Molecular Biology and Genetics in 2004.[36]
As of 2021, she is Distinguished Professor of Molecular, Cellular, and Developmental Biology atUC Santa Cruz.[37]
Greider's lab employs both student and post-doctoral trainees[38] to further examine the relationships between the biology of telomeres and their connection to disease.[36] Greider's lab uses a variety of tools includingyeast,mice, and biochemistry to look at progressive telomere shortening.[39] Greider's lab is also researching howtumor reformation can be controlled by the presence of short telomeres.[39] The lab's future work will focus more on identifying the processing and regulation of telomeres and telomere elongation.[39]
^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.PMID9560153.S2CID4385788.
^NAS OnlineArchived December 9, 2006, at theWayback Machine ("For her pioneering biochemical and genetic studies of telomerase, the enzyme that maintains the ends of chromosomes in eukaryotic cells.")
