Richard P. Lifton, M.D., Ph.D.

Tuesday, Sept. 26, 2006, 9:15 a.m. – 9:45 a.m.

Schiciano Auditorium, Fitzpatrick CIEMAS Building

Many common human diseases are sufficiently multifactorial that their causes are poorly understood, and in some cases even the organs in which primary abnormalities lie have been unknown. In this setting, identification of extreme genetic outliers in the population has the potential to lead to identification of rate-determining pathways that whose variation impacts these traits. These key pathways may identify the key sites at which therapeutic intervention will have the greatest impact on disease treatment or prevention. By collection of such extreme outliers from around the globe, we have identified more than 20 disease genes, including genes that have large effects on blood pressure, bone density, pH and electrolyte homeostasis. These have established the key role of variation in renal salt handling in blood pressure homeostasis, the role of Wnt signaling in bone density, and the role of claudin proteins in paracellular electrolyte flux. These findings have implications for the treatment of both these rare disorders and their common forms.

Richard Lifton is Chairman of the Department of Genetics at Yale University School of Medicine where he is also a Sterling Professor of Internal Medicine, and Molecular Biophysics and Biochemistry and an investigator of the Howard Hughes Medical Institute. He is Director of the Yale Center for Human Genetics and Genomics and Director of the Yale Specialized Center of Research in Hypertension. He received his B.A. from Dartmouth College, the M.D. and Ph.D. degrees from Stanford, and was resident and chief resident in internal medicine at Brigham and Women’s Hospital.

 

Dr. Lifton's laboratory has used molecular genetic analysis to dissect physiologic processes that regulate cardiovascular function in humans, with an emphasis on blood pressure regulation. By coupling characterization of hundreds of families from around the world with human genetic studies, his group has mapped over 30 human disease genes and has identified functional mutations underlying 22 of these. These have provided new insight into the mechanisms underlying hypertension, stroke, osteoporosis, and renal diseases including disorders of electrolyte and pH homeostasis.

 

Most significantly, by the study of rare families with Mendelian forms of severely high or severely low blood pressure, his laboratory has identified mutations in eight genes that raise blood pressure and eight genes that lower blood pressure. Intriguingly, these genes all converge on the same final common pathway, altering net renal salt reabsorption, and provide definitive evidence that mutations that increase net salt balance raise blood pressure in humans. These studies have provided new insight into integrated physiology and pathophysiology that have impacted therapeutic approaches to hypertension in the general population; equally importantly, they have identified new targets and pathways for development of novel therapeutic agents.

 

Dr. Lifton has served as Chair of the NIH Advisory Committee for Large Scale Genomic Sequencing, a member of the Public Policy Committee of the American Society for Cell Biology and the National Advisory Council for the National Human Genome Research Institute.

 

His awards include the Basic Science Prize of the American Heart Association, the Homer Smith Award of the American Society of Nephrology, the Novartis Award for Hypertension Research of the American Heart Association Council for High Blood Pressure Research, and the Medical Research Award of the Pasarow Foundation. He is a member of the National Academy of Sciences and the Institute of Medicine.