Rick Lifton, M.D., Ph.D.
Sterling Professor and Chairman of Genetics
Professor of Molecular Biophysics and Biochemistry
Professor of Medicine
Howard Hughes Medical Institute

B.A., 1975: Dartmouth College
M.D., 1982: Stanford University
Ph.D., 1986: Stanford University
Residency and Chief Residency: Brigham and Women's Hospital
Fellowship: Brigham and Women s Hospital

E-mail: richard.lifton@yale.edu

The common human diseases that account for the vast majority of morbidity and mortality in human populations are known to have underlying inherited components. Advances in
human genetics have made the identification of genetic variants contributing to these traits feasible. Such identification promises to revolutionize the diagnostic and therapeutic approaches to these disorders. We have focused on genes causing renal disease. To date, we have identified mutations underlying 20 human diseases; these include six that raise blood pressure and eight that lower blood pressure in humans. These include diseases such as Liddle’s syndrome, Bartter’s syndrome, Gitelman’s syndrome, and Pseudohypoaldosteronism type I and type II. Intriguingly, all of these mutations alter blood pressure by changing net salt reabsorption in the kidney, identifying this as a key pathway for the regulation of blood pressure. We have also identified three genes that when mutated result in hypomagnesemia. One of these represents the first identified component of a specific paracellular pathway, mediating the selective flux of magnesium via the paracellular route through the tight junctions of the thick ascending limb of Henle. We have also mapped additional loci that contribute to multifactorial traits in humans such as IgA nephropathy and end-stage renal disease, and are attempting to identify underlying disease-causing mutations. These findings are yielding new insight into normal and disease biology, are identifying new pathways underlying disease pathogenesis, and are identifying new targets for development of novel therapeutics.

PubMed Search for articles by faculty member

References

Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ reabsorption. Science, 285:103-106, 1999.

Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai TF, Sigler P, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science, 289:119-123, 2000.

Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP. Human Hypertension Caused by Mutations in WNK Kinases. Science, 293:1107-112, 2001.

Lifton RP, Gharavi A, Geller DS. Molecular mechanisms of human hypertension. Cell, 104:545-556, 2001.

Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein 5. New Engl J Med. 346:1513-1521, 2002.