Kenneth E. White, Ph.D.
Associate Professor of Medical and Molecular Genetics
- B.S. Biology 1988, Binghamton University, Vestal NY
- Ph.D. 1997, Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH (Fellow of the Albert J. Ryan Foundation)
- 1997-1999 Postdoctoral Fellow, Indiana University School of Medicine, Department of Medicine, Endocrine Division (1998-2000, NIH NRSA Postdoctoral Fellow)
- 1999-2003, Research Associate and Assistant Scientist, Indiana University School of Medicine, Department of Medicine, Endocrine Division
Dr. White's laboratory is primarily interested in the molecular genetics of metabolic bone diseases. Dr. White played an instrumental role in the positional cloning of the fibroblast growth factor-23 (FGF23) gene and determining that missense mutations in FGF23 are responsible for the human phosphate wasting disorder autosomal dominant hypophosphatemic rickets (ADHR). FGF23 is a novel secreted hormone that may have direct effects on kidney and on bone. We have recently discovered that recessive, inactivating mutations in FGF23 are responsible for familial tumoral calcinosis (TC), a disorder with a reciprocal phenotype to ADHR. In addition, our group collaboratively determined that mutations in fibroblast growth factor receptor-1 (FGFR1) are responsible for osteoglophonic dysplasia (OGD).
FGF23 is over produced by tumors that cause tumor induced osteomalacia (TIO), a syndrome that is similar to ADHR, indicating that FGF23 is a critical regulator of mineral metabolism. FGF23 is also expressed by cell lines that are associated with leukemia. The roles of FGF23 as a growth factor in cancer are unknown, and we are attempting to understand FGF23 regulation by steroid hormones.
Several active areas of research are presently being taken. We developed a knock-in animal model of ADHR, and are using in vitro approaches as tools for asking questions regarding the roles of FGF23, the FGFRs, and the FGF23 co-receptor *Klotho in situations of normal and abnormal mineral metabolism. The experimental designs in Dr. White's lab will be undertaken with regard to the long-term goal of application to human disorders as well as for the understanding of basic bone and renal cell biology. The study of these novel human mutations provides the opportunity to cross disciplines and to widen our understanding of skeletal biology as well as oncology.
PUBLICATIONS
E.G. Farrow, X. Yu, L.J. Summers, S.I. Davis, J.C. Fleet, M.R. Allen, A.G. Robling, K.R. Stayrook, M.J. Magers, H.J. Garringer, R. Vidal, R.J. Chan, C.B. Goodwin, S. Hui, M. Peacock, and K.E. White. Altered Fgf23 proteolytic regulation causes late-onset hypophosphatemia in an ADHR mouse model. 2011. Proceedings of the National Academy of Sciences (In press).
E.G. Farrow and K.E. White, Recent advances in renal phosphate handling. 2010. Nature Reviews Nephrology. 6(4):207-17.
E.G. Farrow, L.J. Summers, S.C. Schiavi, J. McCormick, D. Ellison, and K.E. White. Renal FGF23-mediated activity involving Mapk and Wnt: Effects of the Hyp mutation. 2010. J Endocrinol. 207(1):67-75.
E.G. Farrow, S.I. Davis, L.J. Summers, and K.E. White. Initial FGF23-mediated signaling occurs in the distal convoluted tubule. 2009. Journal of the American Society of Nephrology; Rapid Communication: 20(5):955-60.
R. Goetz, A. Beenken, O.A. Ibrahimi, J. Kalinina, S.K. Olsen, A.V. Eliseenkova, C. Xu, T. Neubert, F. Zhang, R.J. Linhardt, X. Yu, K.E. White, T. Inagaki, S.A. Kliewer, M. Yamamoto, H. Kurosu, Y. Ogawa, M. Kuro-O, B. Lanske, M.S. Razzaque, M. Mohammadi. Molecular insights into the Klotho-dependent, endocrine mode of action of FGF19 subfamily members. Molecular and Cellular Biology, 2007, 27(9):3417-28.
J.Q. Feng, L.M. Ward, S. Liu, Y. Lu, B. Yuan, X. Yu, F. Rauch, Y. Xie, S.I. Davis, S. Zhang, H. Rios, M.K. Drezner, L.D. Quarles, L.F. Bonewald, and K.E. White. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nature Genetics. 2006, 38(11):1310-5.
K.E. White, J.M. Cabral, S.I. Davis, T. Fishburn, W.E. Evans, S. Ichikawa, J. Fields, X. Yu, N.J. Shaw, N.J. McLellan, C. McKeown, D. FitzPatrick, K. Yu, D.M. Ornitz, and M.J. Econs. Mutations causing osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation. American Journal of Human Genetics. 2004. 28;76(2):361-367.
K.B. Jonsson, R. Zahradnik, T. Larsson, K.E. White, T. Sugimoto, Y. Imanishi, T. Yamamoto, G. Hampson, A. Miyauchi, M. J. Econs, J. Lavigne, and H. Jüppner. Development of an enzyme-linked two-site immunometric assay for FGF-23: elevated circulating concentrations in oncogenic osteomalacia and X-linked hypophosphatemic rickets. The New England Journal of Medicine, 2003; 348(17):1656-1663.
K.E. White, W.E. Evans, J.L.H. O'Riordan, M.C. Speer, M.J. Econs, B. Lorenz-Depiereux, M. Grabowski, T. Meitinger, T.M. Strom. Autosomal dominant hypophosphatemic rickets is associated with mutations in FGF23. Nature Genetics, 2000; 26(3), 345-348.
