About

Carol Greider is a Distinguished Professor of Molecular, Cell and Developmental Biology. She earned her B.A. in Biology from the University of California, Santa Barbara, and her Ph.D. in Molecular Biology from the University of California, Berkeley. She is a Fellow at Cold Spring Harbor Laboratory and was awarded the Nobel Prize in Physiology or Medicine in 2009. Her professional contact is cgreider@ucsc.edu. The GreiderLab, led by Professor Greider, has a significant impact on the scientific community, particularly in the field of telomere and telomerase research, as evidenced by the extensive academic genealogy and alumni network associated with her lab.

Research topics

• Biology
• Genetics
• Computational biology

Selected publications

• Complete genomes of a multi-generational pedigree to expand studies of genetic and epigenetic inheritance

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-16 · 2 citations

  articleOpen access

  Pedigree analysis remains the gold standard for rare disease diagnostics, yet whole genome sequencing studies typically omit critical regions like centromeres, telomeres, and acrocentric chromosome p-arms. Here, we present telomere-to-telomere (T2T) reference genomes for four self-identified African American individuals of admixed ancestry spanning three generations. Our parent-of-origin assigned, chromosome-level assemblies revealed precise meiotic recombination breakpoints in previously inaccessible regions, including recombination events across acrocentric and subtelomeric sequences. Centromeric regions were highly stable, with multi-megabase arrays inherited intact across three generations, while the position of kinetochore assembly sites remained consistent and predominantly associated with the p-arm proximal region. The relative lengths of telomeres on individual chromosomes were maintained across generations. Using a targeted rDNA assembly approach, we reconstructed a complete megabase-scale ribosomal DNA (rDNA) array corresponding to the paternal chromosome 14. This openly available pedigree provides a benchmark dataset for studying recombination and genetic and epigenetic variation across the complete genome.

  PublisherDOI

• Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

  Nature Communications · 2024-05-24 · 7 citations

  reviewOpen accessCorresponding

  Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

  PublisherOA PDFDOI

• Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes

  UNC Libraries · 2024-10-16

  articleOpen access
  PublisherDOI

• Human telomere length is chromosome end–specific and conserved across individuals

  Science · 2024-04-11 · 77 citations

  articleOpen accessSenior authorCorresponding

  Short telomeres cause age-related disease, and long telomeres contribute to cancer; however, the mechanisms regulating telomere length are unclear. We developed a nanopore-based method, which we call Telomere Profiling, to determine telomere length at nearly single-nucleotide resolution. Mapping telomere reads to chromosome ends showed chromosome end-specific length distributions that could differ by more than six kilobases. Examination of telomere lengths in 147 individuals revealed that certain chromosome ends were consistently longer or shorter. The same rank order was found in newborn cord blood, suggesting that telomere length is determined at birth and that chromosome end-specific telomere length differences are maintained as telomeres shorten with age. Telomere Profiling makes precision investigation of telomere length widely accessible for laboratory, clinical, and drug discovery efforts and will allow deeper insights into telomere biology.

  PublisherOA PDFDOI

• Validation of human telomere length trans-ancestry meta-analysis association signals identifies <i>POP5</i> and <i>KBTBD6</i> as novel human telomere length regulation genes

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-07-14 · 1 citations

  preprintOpen access

  Abstract Telomere length genome-wide association studies (GWAS) have become well-powered to detect novel genes in telomere length regulation. However, no prior work has validated these putative novel genes to confirm the contribution of GWAS loci to telomere length regulation. We conducted a trans-ancestry meta-analysis of 211,369 individuals. Through enrichment analyses of chromatin state and cell-type heritability we identified blood and immune cells as the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 , a component of an E3 ubiquitin ligase complex, and POP5 , a component of the Ribonuclease P/MRP complex, and demonstrating that both lengthened telomeres as predicted by our statistical analyses. CRISPR/Cas9 deletion of the predicted causal regions of these association peaks in K562 immortalized blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5 , respectively. Together our results demonstrate the utility of telomere length GWAS in the identification of novel telomere length regulation mechanisms and highlight the importance of the proteasome-ubiquitin pathway in telomere length regulation.

  PublisherOA PDFDOI

• Human telomere length is chromosome specific and conserved across individuals

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-12-22 · 4 citations

  preprintOpen accessSenior authorCorresponding

  Short telomeres cause age-related disease and long telomeres predispose to cancer; however, the mechanisms regulating telomere length are unclear. To probe these mechanisms, we developed a nanopore sequencing method, Telomere Profiling, that is easy to implement, precise, and cost effective with broad applications in research and the clinic. We sequenced telomeres from individuals with short telomere syndromes and found similar telomere lengths to the clinical FlowFISH assay. We mapped telomere reads to specific chromosome end and identified both chromosome end-specific and haplotype-specific telomere length distributions. In the T2T HG002 genome, where the average telomere length is 5kb, we found a remarkable 6kb difference in lengths between some telomeres. Further, we found that specific chromosome ends were consistently shorter or longer than the average length across 147 individuals. The presence of conserved chromosome end-specific telomere lengths suggests there are new paradigms in telomere biology that are yet to be explored. Understanding the mechanisms regulating length will allow deeper insights into telomere biology that can lead to new approaches to disease.

  PublisherOA PDFDOI

• TPP1 promoter mutations cooperate with TERT promoter mutations to lengthen telomeres in melanoma

  Science · 2022-11-10 · 39 citations

  articleOpen accessCorresponding

  Overcoming replicative senescence is an essential step during oncogenesis, and the reactivation of TERT through promoter mutations is a common mechanism. TERT promoter mutations are acquired in about 75% of melanomas but are not sufficient to maintain telomeres, suggesting that additional mutations are required. We identified a cluster of variants in the promoter of ACD encoding the shelterin component TPP1. ACD promoter variants are present in about 5% of cutaneous melanoma and co-occur with TERT promoter mutations. The two most common somatic variants create or modify binding sites for E-twenty-six (ETS) transcription factors, similar to mutations in the TERT promoter. The variants increase the expression of TPP1 and function together with TERT to synergistically lengthen telomeres. Our findings suggest that TPP1 promoter variants collaborate with TERT activation to enhance telomere maintenance and immortalization in melanoma.

  PublisherOA PDFDOI

• Chromosome structure and function

  Oxford University Press eBooks · 2021-02-25 · 1 citations

  book-chapter

  This chapter examines the structure and function of chromosomes. Each chromosome contains many genes embedded within a single DNA molecule; between the genes lie stretches of intergenic DNA. Moreover, each organism contains a characteristic number of chromosomes in each cell. Diploid cells contain two sets of chromosomes in each cell while haploid cells contain just a single set of chromosomes. Chromosomes in all organisms are associated with proteins that help to condense and organize the DNA molecules inside the cell. The basic building block of chromatin is the nucleosome, which consists of around 146 bp of DNA, wrapped twice around the histone octamer in a left-handed manner. The chapter then looks at DNA methylation, the elements required for chromosome function, the centromere and the telomere, and chromosome architecture in the nucleus.

  PublisherDOI

• DNA replication

  Oxford University Press eBooks · 2021-02-25

  book-chapter

  This chapter evaluates DNA replication, which occurs in three distinct phases: initiation, elongation, and termination. Initiation of replication in bacteria occurs at a unique chromosomal location called an origin, which is recognized by specific proteins. Initiation of replication in eukaryotes, in contrast, usually occurs stochastically at sites marked in the genome by binding of the pre-replication complex. New DNA strands are initiated by RNA or combined RNA and DNA primers, which are synthesized by primase in bacteria and the polymerase α-primase complex in eukaryotes. After their initial synthesis, the primers are then elongated by the replicative DNA polymerase. The termination of replication occurs when two replication forks traveling in opposite directions meet. The chapter then looks at the regulation of the initiation of DNA replication, the end-replication problem, and the replication of chromatin.

  PublisherDOI

• Transcription

  Oxford University Press eBooks · 2021-02-25

  book-chapter

  This chapter addresses transcription, which is a key step in gene expression. In order for the information in the genome to be expressed, the cell must synthesize an RNA copy of the DNA. The RNA polymerase enzyme catalyses the synthesis of the RNA from ribonucleotide triphosphate precursors, using the DNA template strand to assemble a copy of the coding strand. RNA is synthesized from the 5' to the 3' end in a defined series of events known as the transcription cycle: initiation, elongation, and termination. Transcription begins with isomerization of RNA polymerase to form the open complex, in which the DNA strands are separated and synthesis of the RNA begins, using the template strand to position the incoming ribonucleotide triphosphates. RNA polymerase may first go through several cycles of abortive initiation, producing very short transcripts, before breaking free of the promoter and entering into the elongation phase.

  PublisherDOI

Recent grants

• Project 2: Splicing Dysregulation in Cancer

  NIH · $257.8M · 1997–2028

• NIH Grant R01AG009383

  NIH · $1.6M · 2001

• Telomeres and Telomerase in Cancer

  NIH · $6.3M · 2017–2024

• NIH Grant R01AG027406

  NIH · $1.9M · 2012

• NIH Grant R01GM043080

  NIH · $6.8M · 2013

Frequent coauthors

• Margaret A. Strong

  Johns Hopkins Medicine

  72 shared

• Mary Armanios

  Johns Hopkins University

  42 shared

• Carla J. Connelly

  Johns Hopkins University

  38 shared

• Samantha L. Sholes

  Johns Hopkins University

  36 shared

• Julian J.‐L. Chen

  Arizona State University

  33 shared

• Calvin B. Harley

  32 shared

• Jonathan K. Alder

  University of Pittsburgh

  30 shared

• Karen R. Prowse

  29 shared

Labs

• GreiderLabPI

  This is meta description

Education

• Ph.D., Molecular Biology

  Johns Hopkins University

  1987

• B.A., Zoology

  Columbia University

  1980