Peter A. Doris, Ph.D.
Professor
Center for Human Genetics
phone 713.500.2414;
fax 713.500.2447
Peter.A.Doris@uth.tmc.edu
Dr. Doris is investigating the genetics and pathophysiologic
mechanisms of common
cardiovascular diseases. His work is focused on high blood pressure,
stroke, and renal injury.
Dr. Doris received his doctoral degree at the University of California and returned to his native England as a Medical Research Council post-doctoral fellow at Cambridge University and the University of Reading. He joined the Institute in the summer of 1997 and is appointed as Professor in the Center for Human Genetics. His research takes a systems biology approach integrating physiology at the organismal, organ and cellular levels with genomic, genetic and proteomic approaches to uncover mechanisms of common cardiovascular diseases.
In spite of much progress, cardiovascular disease remains the leading cause of mortality and chronic disability in our society. High blood pressure (hypertension) is a major force creating cardiovascular disease by causing or exacerbating injury to the blood vessels (atherosclerosis), the heart (heart failure), the brain (stroke) and the kidney (progressive renal disease). The impact of these diseases on public health is often underappreciated. For example, progressive kidney disease resulting in insufficient renal function consumes nearly 7% of all US government Medicare spending (an amount equal to the annual budget of NASA) and causes as many deaths each year as breast and prostate cancer combined.
Part of the risk of cardiovascular disease is inherited. Progress in mapping genes causing disease has created excitement that cardiovascular disease can be understood more fully using genetic approaches. However, the inheritance is not simple and cannot be attributed to single genes. Furthermore, risk, including genetic risk, is partitioned between genes contributing to the damaging force (in the broad population this principally means those elevating blood pressure) and those contributing to the capacity of organs to resist injury. The genetic contours of injury susceptibility are poorly defined. More is known about the genetics of risk for elevated blood pressure (hypertension). However, it has become clear in the last 5 years that gene mapping approaches are struggling to succeed in identifying hypertension genes.
The difficulty of mapping cardiovascular disease risk alleles in the population is not surprising, at least not to a view of genetic susceptibility that incorporates the biology of disease. These diseases result when environmental factors (diet, physical activity, lifestyle, age) interact with genetic susceptibility arising out of normal variation within multiple genes. Furthermore, physiological systems regulating basic cardiovascular functions such as blood pressure are extraordinarily complex and operate across multiple body systems (autonomic nervous system, vascular endothelium, endocrine systems, renal function). This adds to the challenge of identifying susceptibility genes in humans because the total set of genes participating in blood pressure regulation is very large, providing great scope for genetic heterogeneity in population disease risk. The complexity of these gene-gene and gene-environment interactions obstructs the identification of susceptibility genes for cardiovascular disease. Population mapping studies simply appear to lack sufficient power to identify genes because power is eroded through genetic complexity. Consequently, the anticipated progression from disease gene identification by mapping, to understanding disease mechanism to developing new therapeutic approaches has not materialized. Our work focuses on animal models of cardiovascular disease that offer more tractable opportunities for investigation.
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