Aging and Cancer

2011 senior Scholar Award in aging

p53 genes link environmental stressors to adaptive cellular responses, affecting life span and cancer susceptibility. As a protein, p53 acts to regulate the expression of so-called target genes, analogous to an integration device, which responds to stimuli by operating switches that turn sets of... >> MORE

2011 senior Scholar Award in aging

There is a well-documented association of aging with increased incidence of diabetes and cancer, as well as reduced capacity for wound healing and tissue repair. In studies aimed at understanding how cancer genes are regulated in stem cells, we unexpectedly discovered a role for an ancient... >> MORE

2011 senior Scholar Award in aging

The p53 protein is a prominent tumor suppressor, often referred to as the “guardian of the genome”. p53 is stabilized and activated in response to a variety of stress signals and, in turn, activates specific target genes through its function as a conventional transcription factor that binds to... >> MORE

2010 senior Scholar Award in aging
Age is one of the strongest risk factors for cancer. The likelihood of developing a tumor increases dramatically as we age. Yet, nobody knows why that is. Based on spurious observations in various organisms a number of diverse reasons have been suggested to explain aging-associated cancer formation... >> MORE
2009 senior Scholar Award in aging
The naked mole-rat is the longest living rodent with a maximum lifespan exceeding 28 years. In addition to its longevity, the naked mole-rat has extraordinary resistance to cancer as tumors have never been observed in these rodents. The mechanism for cancer resistance in the naked mole-rat is... >> MORE
2008 senior Scholar Award in aging
Our laboratory works with an enzyme called PI3 kinase (PI3K). This enzyme has a long history, having first been discovered in the 1980s due to its role in cancer. We now know that PI3K plays a number of important roles in individual cells and in the physiology of the whole organism. For instance... >> MORE
2006 senior Scholar Award in aging

Naked Mole Rats (NMRs) are the longest-living rodents known; they live >28y in captivity which is ~9x longer than similarly-sized mice. NMRs show attenuated age-related declines in both morphology (e.g. bone loss) and function ( e.g. vascular function). Furthermore, we have never seen any... >> MORE

2006 senior Scholar Award in aging

Cancers arise through the gradual acquisition of mutations in susceptible cells in the body - mutations that wreck the normal mechanisms that restrain cell growth, proliferation, survival movement and invasion and maintain normal architecture and dynamics of our tissue. There is an enormous... >> MORE

2005 senior Scholar Award in aging

The major focus of my laboratory for the last 15 years has been on understanding the functions of a category of genes called tumor suppressors. As their name implies, a primary role of tumor suppressor genes is to prevent the onset of cancers. Cancers are often initiated when cells and their... >> MORE

2003 senior Scholar Award in aging

Normal cells grown in culture have a limited potential to divide and eventually become terminally non-dividing. This is called cell or replicative senescence and is used as a model to study aging at the cell level. Tumor-derived cells, in contrast, divide constantly without control. We have... >> 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

2000 senior Scholar Award in aging

The overall aim of this grant is to provide new methods for the study of gene action in human aging, using cell transplantation techniques applied to human adrenocortical cells. Prior to beginning this grant, we had established methods for genetic modification of bovine adrenocortical cells and... >> MORE

2013 new Scholar Award in aging

A number of genetic studies in lower organisms have identified several pathways as key regulators of lifespan, stress response, and reproductive fitness, including the Insulin-PI3K-AKT-FoxO, target of rapamycin (TOR), and LKB1-AMPK pathways. All these longevity pathways are conserved in mammals... >> MORE

2013 new Scholar Award in aging

Recent advances in technologies for determining DNA sequences have revealed that every human genome contains small deletions, as well as mutations that abolish the function of one of two copies of tens of genes. Such mutations and deletions do not result in complete loss of function, but rather... >> MORE

2013 new Scholar Award in aging

The process of aging involves a progressive decline in physiology and function of our tissues. Current research suggests that we age, in part, due to reduced function of self-renewing stem cells that are required for tissue rejuvenation of many tissue types. Our understanding of why and how stem... >> MORE

2012 new Scholar Award in aging

Although aging is an immensely complicated process, one characteristic of aging is increased susceptibility to cancer, which can result from genetic instability. Our cells are exposed to DNA damaging agents daily, such as UV irradiation, and as we age the ability of our cells to repair these... >> MORE

2011 new Scholar Award in aging

In response to a variety of stress signals, including nutrient deprivation, oxidative stress, dysfunctional telomeres, DNA damage and oncogene overexpression, normally dividing cells can permanently withdraw from the typical cell cycle. These cells are then said to be in a state of cellular... >> MORE

2011 new Scholar Award in aging

The accumulation of somatic (non-heritable) DNA mutations over time is a hallmark and potential mechanism of aging. Current theory postulates that un-repaired, stochastic DNA damage results in random DNA mutations that accumulate over time within individual cells, and are passed on as these... >> MORE

2009 new Scholar Award in aging
In humans, aging is associated with two major life-threatening diseases: neurodegeneration and cancer. A number of theories have been proposed to account for the aging process. The stress theory of aging emphasizes that stressful environments cause cellular damages, disruption of cellular functions... >> MORE
2009 new Scholar Award in aging
The increasing incidence of cancer in the aging population is a major cause of mortality. Other than the accumulation of mutations, there exists no evidence to associate aging with epigenetic instabilities and cancer formation. I propose to build a system to model cancer formation from embryonic... >> MORE
2007 new Scholar Award in aging
The human body is marked by interactions among individual cells, especially between neighboring cells. In young and healthy tissue, neighboring cells modify their internal structure and adhere to each other. This often leads to a collective change of cell morphology. Cell morphological change... >> MORE
2006 new Scholar Award in aging

γ-Secretase has long been regarded as an attractive anti-amyloid therapeutic target for Alzheimer's disease (AD). However, our studies demonstrated that mice with reduced levels of γ-secretase activity (Nct+/- mice and Nct+/-;PS1+/-... >> MORE

2006 new Scholar Award in aging
Eastern grey squirrel is one of the longest-lived rodents. Its maximum documented lifespan is 23 years, which is almost 10 times longer than that of a mouse. Since squirrel is related to classical short-lived laboratory rodents such as mouse and rat, squirrel is an ideal model organism to... >> MORE
2006 new Scholar Award in aging
Our lab studies the basic mechanisms of transcriptional regulationówhat turns gene expression ìon or offî in human cells. A major aspect of our work involves a protein known as p53, which works primarily by triggering changes in gene expression patterns in response to specific cellular cues. Many... >> 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

2002 new Scholar Award in aging

Progressive loss of neurons in the brain is a hallmark of many neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. The only known risk factor for the majority of such patients is aging. Nonetheless, most people do not develop these disorders during aging, so other... >> MORE

2000 new Scholar Award in aging

One major advance in the study of mammalian aging was the discovery made by Hayflick in the 1960's. He observed that normal human cells had a finite lifespan in vitro and could execute only a limited number of cell divisions. Beyond this limit, cells undergo an irreversible growth arrest... >> MORE