2011 senior Scholar Award in aging

Aging is a complex process that occurs at both cellular and organismal levels. As cells age, the ends of their chromosomes, so called telomeres, are gradually eroded. Eroded telomeres are recognized by cells as broken DNA ends, eliciting checkpoint responses and a senescence cellular state in... >> MORE

2009 senior Scholar Award in aging
Telomeres are specialized structures present at the ends of all chromosomes and are essential for maintaining chromosome integrity; thus they have been implicated in mechanisms involved in aging. Telomeres contain a long stretch of DNA with a simple, repeated TTAGGG sequence (telomeric repeat or... >> MORE
2008 senior Scholar Award in aging
We have studied the role of genomic instability in the determination of lifespan in yeast as a model for replicative senescence in human cells. We recently defined a genetic network of 322 genes and 826 interactions that preserve genome stability during DNA replication. This network suggests that... >> MORE
2003 senior Scholar Award in aging

Telomeres are specialized capping structures on chromosomes that play important roles in aging, cancer and genome stability. Normal cells do not possess the specialized enzyme telomerase that functions to synthesize and maintain telomere length with each cell division. Thus, cell division is... >> MORE

2003 senior Scholar Award in aging

The biological processes that cause human aging are complex and remain poorly understood. Two general mechanisms have been proposed to explain the aging of human tissue. The first postulates that aging is caused by the accumulated damage that cells within our tissues sustain due to various... >> MORE

2002 senior Scholar Award in aging
Normal human cells growing outside the body in culture media have a finite ability to reproduce. An internal "clock" forces them eventually to stop dividing and enter an irreversible state of proliferative arrest termed "replicative senescence" (RS). There is evidence that RS represents aging at... >> MORE
2002 senior Scholar Award in aging

One of the major functions of cellular senescence is to serve as a brake against malignancy. At least 3-6 mutations are required to form a tumor. Each mutation probably requires 20-30 doublings for the initial mutation, elimination of the remaining wild-type allele (for recessive tumor... >> MORE

2001 senior Scholar Award in aging
The telomeric caps at the ends of chromosomes are essential for maintaining the integrity of eukaryotic genomes. Two processes must be fully operational in order to prevent telomere dysfunction: chromosome ends need to be fully replicated and these termini also need to be protected from the... >> MORE
2000 senior Scholar Award in aging
Our research has focused on the long range remodeling of DNA as it undergoes replication, recombination, and repair. Such topics remain one of the most difficult areas to study using standard molecular tools but can be approached by direct electron microscopic (EM) visualization. Telomeres are... >> MORE
1999 senior Scholar Award in aging
In collaboration with Jack Griffith (UNC) we have found that human telomeres form large duplex loops (t-loops). We propose that t-loops represent the mechanism by which telomere ends are masked from the cellular machinery that detects DNA breaks. Our working hypothesis is that telomere shortening... >> MORE
1998 senior Scholar Award in aging
Telomeres are structures composed of a specific DNA sequence and specialized proteins that cap the ends of chromosomes. Telomeres stabilize the chromosome, and thus ensure that the genome is maintained in a normal, stable state. Normal human cells lose a small amount of telomeric DNA each time... >> MORE
1998 senior Scholar Award in aging
Dr. Elledge has an interesting hypothesis that could unify the telomere and DNA damage theories of cell senescence. He will study the regulation of the ARF1 gene over time, and its interaction with DNA damage, to cause cell senescence. >> MORE
1998 senior Scholar Award in aging

We are interested in understanding how cells maintain their chromosomes, the structures that transmit genetic information. Specifically, we are interested in the ends of chromosomes, known as telomeres. Telomeres are specialized structures that are essential for the chromosomes maintenance. When... >> MORE

1998 senior Scholar Award in aging
Telomere length appears to be critically involved in cellular senescence and in cellular immortality. Telomerase shortening results in cellular senescence, while stabilization of telomere length results in cellular immortality and cancer. Regulation of telomere length is usually, but not always,... >> MORE
2011 new Scholar Award in aging

Aging is characterized by a progressive decline of tissue function associated with loss of regenerative potential. With age stem cell compartments are progressively less efficient in maintaining tissue homeostasis, and tissues undergo atrophy. These changes have been associated with critical... >> MORE

2010 new Scholar Award in aging
Nuclear function and nuclear organization are inextricably linked. The nucleoskeleton is a protein network that maintains the structural integrity of the nucleus and provides a framework for its functional organization. The intermediate filament lamin A/C is an integral component of the... >> MORE
2009 new Scholar Award in aging
Telomeric tracts shorten upon each cell division and critically short telomeres eventually trigger cell cycle arrest and apoptosis. Therefore, telomere length limits how many times human somatic cells can replicate and determines the lifespan of tissues. One way to circumvent aging in tissues is... >> MORE
2008 new Scholar Award in aging

Fully stretched out, the DNA in each mammalian cell extends roughly six feet in length. To fit within the confines of a cell, this DNA is wound around specialized proteins and thereby condensed into a compact form called chromatin. The structure of chromatin is tightly regulated to modulate... >> MORE

2007 new Scholar Award in aging
Human aging is associated by a progressive loss of tissue structure and function however, the cause of tissue degeneration remains poorly understood. One model that might partly explain the functional decline of various organ systems with increasing age is that cells essential for tissue function... >> MORE
2007 new Scholar Award in aging
The enzyme telomerase, which replicates telomeres, is thought to be key to cellular immortality. Telomere shortening leads to cellular aging, a process that can be reversed by restoration of the telomeric structure. Meanwhile, up to 90% of human tumor cells show high levels of telomerase activity... >> MORE
2006 new Scholar Award in aging
Maintenance of the genome is critical for the survival and health of an organism. Genomic mutations and alterations promote cancer, and the incidence of cancer increases exponentially with age. My lab is investigating the mechanisms of genomic instability associated with aging and diseases... >> MORE
2004 new Scholar Award in aging

Telomeres are protein-DNA structures that prevent the termini of chromosomes from being recognized as DNA damage-induced chromosome breaks. Telomere maintenance has been proposed to play a central role in human aging by limiting the replicative potential of somatic cell populations and... >> MORE

2003 new Scholar Award in aging

Aging cells and tissues accumulate point mutations and genomic rearrangements, consistent with a failing ability to defend their genomes against DNA damage. Rearrangements result primarily from errors in repair of double-strand breaks (DSBs), which arise commonly by breakage of replication forks... >> MORE

1999 new Scholar Award in aging
Telomeres are specialized structures at the ends of chromosomes that are essential for stability. They are composed of several thousand base pairs of a repeating DNA sequence, (TTAGGG), and proteins that bind specifically to this sequence. In human cells, telomeric DNA is lost each time the cell... >> MORE