David Kingsley

Administrative Appointments

• Director, NIH Center of Excellence in Genomic Science at Stanford: The Genomic Basis of Vertebrate Diversity (2007 - 2012)

Honors and Awards

• Conklin Medal, Society for Developmental Biology (2009)
• Fellow, American Academy of Arts and Sciences (2005)
• Researcher, Howard Hughes Medical Institute (1997 to present)
• Scholar in Biomedical Research, Lucille P. Markey Foundation (1989 to 1996)

Professional Education

Postdoctoral Advisees

Terence Capellini, Felicity Jones, Philip Reno, Haili Zhang

Graduate & Fellowship Program Affiliations

• Developmental Biology
• Neurosciences

Community & International Work

• Stickleback Genome Project and Summer Training Course, Stanford 

Web Site Links

• http://kingsley.stanford.edu

Research Interests

The skeleton is one of the most highly patterned structures in higher organisms. Although built of only a few tissue types, these tissues are molded into beautiful shapes and sizes that illustrate many basic problems in development, morphogenesis, and vertebrate evolution. The skeleton is also critical to human health, with diseases like osteoarthritis and osteoporosis afflicting a large fraction of the human population. To better understand the genetic mechanisms that create, pattern, and repair skeletal tissues, we are using both forward and reverse genetic approaches to study interesting skeletal traits in humans, mice, and stickleback fish.

We have used a combination of high resolution linkage mapping and chromosome walking techniques to isolate several classical mouse skeletal mutations that disrupt skeletal patterning or joint formation. These studies have shown that secreted signalling molecules called bone morphogenetic proteins (BMPs) play a key role in controlling formation of both bones and joints during embryonic development. Each of these genes is expressed in strikingly specific patterns that prefigure the formation of particular bones and joints. We have used detailed transgenic and comparative genomic methods to identify the regulatory elements responsible for patterning the expression of these genes during vertebrate skeletal development. The long term goal of these studies is to determine how the body creates, shapes, and maintains particular bones and joints in order to generate a functional skeleton.

We have also used genetic methods to isolate a completely new gene controlling susceptibility to arthritis after birth. The normal product of this gene is a highly conserved multiple pass transmembrane protein found only in vertebrates. We have used a combination of cell culture and biochemical techniques to show that this molecule acts by stimulating transport of the same small molecule that is used in “tartar control” toothpaste...

Publications

• cis-Regulatory changes in Kit ligand expression and parallel evolution of pigmentation in sticklebacks and humans. Miller CT, Beleza S, Pollen AA, Schluter D, Kittles RA, Shriver MD, Kingsley DM. Cell. 2007; 131 (6): 1179-89
• Parallel genetic origins of pelvic reduction in vertebrates. Shapiro MD, Bell MA, Kingsley DM. Proc Natl Acad Sci U S A. 2006; 103 (37): 13753-8
• Widespread parallel evolution in sticklebacks by repeated fixation of Ectodysplasin alleles. Colosimo PF, Hosemann KE, Balabhadra S, Villarreal G, Dickson M, Grimwood J, Schmutz J, Myers RM, Schluter D, Kingsley DM. Science. 2005; 307 (5717): 1928-33
• Genetic and developmental basis of evolutionary pelvic reduction in threespine sticklebacks. Shapiro MD, Marks ME, Peichel CL, Blackman BK, Nereng KS, Jónsson B, Schluter D, Kingsley DM. Nature. 2004; 428 (6984): 717-23
• BMP receptor signaling is required for postnatal maintenance of articular cartilage. Rountree RB, Schoor M, Chen H, Marks ME, Harley V, Mishina Y, Kingsley DM. PLoS Biol. 2004; 2 (11): e355