Ophir Klein M.D., Ph.D.
Genetic regulation of dental stem cells and craniofacial and tooth morphogenesis
Embryonic development is one of the most beautiful processes in nature. However, when developmental processes go awry, then birth defects, cancer and other diseases can result. Our research is centered on understanding how development normally occurs in the hope of one day treating diseases that result from abnormalities in these processes. We focus largely on craniofacial and dental development, as malformations in these organs are among the most common congenital abnormalities and have profound impacts on the lives of patients and their families. We also study normal and perturbed development of the skeleton, taste papillae, external genitalia, gastrointestinal tract, and other organs, and we investigate how embryonic and adult stem cells self-renew and differentiate.
Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. Goodwin AF, Tidyman WE, Jheon AH, Sharir A, Zheng X, Charles C, Fagin JA, McMahon M, Diekwisch TG, Ganss B, Rauen KA, Klein OD. Hum Mol Genet. 2014 Feb 1;23(3):682-92. doi: 10.1093/hmg/ddt455. Epub 2013 Sep 20.
BMI1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor. Biehs B, Hu JK, Strauli NB, Sangiorgi E, Jung H, Heber RP, Ho S, Goodwin AF, Dasen JS, Capecchi MR, Klein OD. Nat Cell Biol. 2013 Jul;15(7):846-52. doi: 10.1038/ncb2766. Epub 2013 Jun 2.
A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, de Sauvage FJ. Nature. 2011 Sep 18;478(7368):255-9. doi: 10.1038/nature10408. Erratum in: Nature. 2012 Feb 2;482(7383):120.
Regulation of tooth number by fine-tuning levels of receptor-tyrosine kinase signaling. Charles C, Hovorakova M, Ahn Y, Lyons DB, Marangoni P, Churava S, Biehs B, Jheon A, Lesot H, Balooch G, Krumlauf R, Viriot L, Peterkova R, Klein OD. Development. 2011 Sep;138(18):4063-73. doi: 10.1242/dev.069195.
FGF signaling regulates the number of posterior taste papillae by controlling progenitor field size. Petersen CI, Jheon AH, Mostowfi P, Charles C, Ching S, Thirumangalathu S, Barlow LA, Klein OD. PLoS Genet. 2011 Jun;7(6):e1002098. doi: 10.1371/journal.pgen.1002098. Epub 2011 Jun 2.