Abbas T.,University of Virginia |
Keaton M.A.,University of Virginia |
Keaton M.A.,Metabolon |
Dutta A.,University of Virginia
Cold Spring Harbor Perspectives in Biology | Year: 2013
One of the fundamental challenges facing the cell is to accurately copy its genetic material to daughter cells. When this process goes awry, genomic instability ensues in which genetic alterations ranging from nucleotide changes to chromosomal translocations and aneuploidy occur. Organisms have developed multiple mechanisms that can be classified into two major classes to ensure the fidelity of DNA replication. The first class includes mechanisms that prevent premature initiation of DNA replication and ensure that the genome is fully replicated once and onlyonce during each division cycle. These include cyclin-dependent kinase (CDK)-dependent mechanisms and CDK-independent mechanisms. Although CDK-dependent mechanisms are largely conserved in eukaryotes, higher eukaryotes have evolved additional mechanisms that seem to play a larger role in preventing aberrant DNA replication and genome instability. The second class ensures that cells are able to respond to various cues that continuously threaten the integrity of the genome by initiating DNA-damage-dependent "checkpoints" and coordinating DNA damage repair mechanisms. Defects in the ability to safeguard against aberrant DNA replication and to respond to DNA damage contribute to genomic instability and the development of human malignancy. In this article, we summarize our current knowledge of how genomic instability arises, with a particular emphasis on how the DNA replication process can give rise to such instability. © 2013 Cold Spring Harbor Laboratory Press; all rights reserved.
Metabolon | Date: 2015-11-23
Biomarkers relating to metabolic age are provided, as well as methods for using such biomarkers as biomarkers for determining metabolic age. In addition, methods for modulating the metabolic age of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for metabolic age.
Metabolon | Date: 2014-05-13
Biomarkers of kidney function and methods for using said biomarkers for assessing kidney function, monitoring kidney function, diagnosing acute kidney injury, and diagnosing chronic kidney disease are provided. Also provided are suites of small molecule entities as biomarkers for chronic kidney disease.
Metabolon | Date: 2014-01-16
Biomarkers relating to insulin resistance and insulin resistance-related disorders are provided, as well as methods for using such biomarkers as biomarkers for insulin resistance, dysglycemia, type-2 diabetes, and cardiovascular disease. In addition, methods for monitoring the respective disorders or conditions of a subject are also provided. Also provided are suites of small molecule entities as biomarkers for insulin resistance, dysglycemia, type-2 diabetes, and cardiovascular disease.
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.3-3 | Award Amount: 7.91M | Year: 2012
Type 2 diabetes (T2DM) is preventable by sustained changes in diet and physical exercise. Despite this, modern societies are already approaching 10% population prevalence of diabetes, and another 15% with pre-diabetes. The costs of T2DM are huge, approaching 10% of all health costs. Prevention of diabetes is a priority for national healthcare agencies and for the health insurance industry. Investment in prevention and lifestyle programmes requires a solid evidence-base for targeting and customising these interventions in a cost-effective manner. Translation of the findings from T2DM prevention studies to the benefit of general public health has not yet been possible. DEXLIFE will identify novel diagnostic and predictive biomarkers (i) to detect the progression toward diabetes in high risk individuals and (ii) that are responsive to lifestyle interventions known to be effective in diabetes prevention. New biomarkers alone will be insufficient to alter the course of diabetes progression. We bring a strong translational focus to this proposal, by setting the main intervention in the real-life context of a major health insurance system. The accumulated phenotyping repertoire from an extensive panel of omic analyses will be refined and modelled into a new diagnostic panel for the allocation of high risk subjects to individualised preventive regimens. Our multi-disciplinary team has a strong track record in clinical diabetes and metabolism. Several unique clinical cohorts will provide the basis for a series of clinical, physiological and mechanistic investigations, which will identify, monitor and analyse the impact of biomarkers over time. An exercise and dietary intervention study will be included in two specific cohorts, enabling us to assess the impact of such interventions on plasma biomarkers and functional tissue-based markers. Project clinical and industry partners will support the translation of our findings into clinical practice.