Ophir Klein, PhD, MD

Chief, Division of Genetics
Chair, Division of Craniofacial Anomalies
Director, Program in Craniofacial Biology
Professor
Department of Orofacial Sciences
Department of Pediatrics
+1 415 476-4719

Ophir Klein is Professor of Orofacial Sciences and Pediatrics, the Larry L. Hillblom Distinguished Professor in Craniofacial Anomalies, and the Charles J. Epstein Professor of Human Genetics at the University of California, San Francisco (UCSF). He serves as Chief of the Division of Medical Genetics, Chair of the Division of Craniofacial Anomalies, Medical Director of the Craniofacial Center, and Director of the Program in Craniofacial Biology.

The Klein laboratory focuses on understanding how organs form in developing embryos and how they regenerate in adults. When developmental and regenerative processes go awry, then birth defects, cancer and other diseases can result. The group's research is centered on understanding how development and regeneration normally occur in the hope of one day treating diseases that result from abnormalities in these processes.

A central focus in the lab is 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. The maintenance, repair and growth of many adult organs, such as the bone marrow, skin, brain, and gastrointestinal tract, depend on tissue-specific populations of stem cells. The lab uses the rodent incisor as a model system to understand adult stem cells. Unlike human teeth, the rodent incisor grows continuously throughout the life of the animal. We are working to understand the molecular processes that regulate the behavior of these stem cells, including their capacity to self-renew as well as to differentiate into the various cellular components of the tooth. We intend to use the insights provided by our experiments in mice to guide us in the use of stem cells in regenerating dental and craniofacial tissues as a paradigm for developing replacement organs.

Another major area of study is regeneration of the gastrointestinal tract. The amazing ability of the mammalian gastrointestinal epithelium to renew has long fascinated biologists. Our research aims to address fundamental questions in this field, including the identity, regulation and plasticity of intestinal stem cells.

Finally, the laboratory is interested in how positive and negative modulators of signaling affect development, homeostasis and cancer. We are studying the roles of these molecules in the patterning and outgrowth of teeth, taste papillae, craniofacial and long bones, external genitalia, skin, and other organs. We are also examining the roles of these molecules in embryonic and adult stem cells.

Primary Thematic Area: 
Developmental & Stem Cell Biology
Secondary Thematic Area: 
Human Genetics
Research Summary: 
Developmental genetics of organ formation and regeneration

Websites

Featured Publications: 

Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor.

Development (Cambridge, England)

Seidel K, Ahn CP, Lyons D, Nee A, Ting K, Brownell I, Cao T, Carano RA, Curran T, Schober M, Fuchs E, Joyner A, Martin GR, de Sauvage FJ, Klein OD

A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable.

Nature

Tian H, Biehs B, Warming S, Leong KG, Rangell L, Klein OD, de Sauvage FJ

BMI1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor.

Nature cell biology

Biehs B, Hu JK, Strauli NB, Sangiorgi E, Jung H, Heber RP, Ho S, Goodwin AF, Dasen JS, Capecchi MR, Klein OD

Replaying evolutionary transitions from the dental fossil record.

Nature

Harjunmaa E, Seidel K, Häkkinen T, Renvoisé E, Corfe IJ, Kallonen A, Zhang ZQ, Evans AR, Mikkola ML, Salazar-Ciudad I, Klein OD, Jernvall J

Continuously growing rodent molars result from a predictable quantitative evolutionary change over 50 million years.

Cell reports

Tapaltsyan V, Eronen JT, Lawing AM, Sharir A, Janis C, Jernvall J, Klein OD

Opposing activities of Notch and Wnt signaling regulate intestinal stem cells and gut homeostasis.

Cell reports

Tian H, Biehs B, Chiu C, Siebel CW, Wu Y, Costa M, de Sauvage FJ, Klein OD

Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis.

Developmental cell

Prochazka J, Prochazkova M, Du W, Spoutil F, Tureckova J, Hoch R, Shimogori T, Sedlacek R, Rubenstein JL, Wittmann T, Klein OD