Professor • Post Docs • Technical Staff • Students • Join Our Lab
Jonathan M. (Jon) Graff, M.D., Ph.D.
M.D., Ph.D., Duke University - 1989,1990
Associate Professor, Departments of Developmental Biology, Molecular Biology and Internal Medicine
Genetics and Development
Office: (214) 648-1481, (214) 648-1482, (214) 648-1612
FAX: (214) 648-1960
Building NB, Room 5.228
Email: Jon.Graff@utsouthwestern.edu
A central task in developmental biology is the elucidation of the mechanisms through which a radially symmetric egg becomes a patterned adult. We are interested in the endogenous signals and signaling pathways that control cell fate. That is, we are trying to uncover the molecular mechanisms that tell a cell whether to become for example, a brain cell, a fat cell, or a disease cell. During embryogenesis, the signaling pathways are normal while, during disease states, the pathways are abnormal. We study both development and animal models of disease with the idea that the two systems will provide mutually synergistic information. We primarily study these processes by exploiting the unique advantages provided by in vivo analyses in four model organisms: C. elegans (worms), Drosophila (flies), Xenopus laevis (frogs), and mice.
A major focus of the lab is to identify and then characterize new molecules that control developmental fates. Much of our invertebrate efforts are directed towards gene discovery through genetic screens. In addition, we have developed a series of unique techniques to identify vertebrate genes. These new methodologies include functional expression cloning, a novel post-genomics approach, as well as our recently discovered method to identify cell-surface and secreted molecules. To extend our studies from development to models of disease, we disrupt the developmentally important molecules through homologous recombination in the mouse. For example, we studied Smad genes because of their importance during embryogenesis. In addition, Smads are mutated in many human cancers including colon cancer, which affects 5% of Americans. To develop an animal model of colon cancer we generated Smad knockout mice. We found that 100% of Smad3 mutant mice develop metastatic colon cancer that in many important ways mimics the human disease. These studies provide a paradigm for the direction of our research efforts.
Awards & Honors:
Basil O'Connor Starter Scholar Research Award
Charles E. Culpeper Medical Scholar Award
Leukemia & Lymphoma Society Scholar Award
American Cancer Society Scholar Award
Selected References:
Graff, J.M., Thies, R.S., Song, J.J., Celeste, A.J., and Melton, D.M. Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo. Cell 79, 169-179, 1994.
Graff, J.M., Bansal, A., and Melton, D.M. Xenopus Mad proteins transduce distinct subsets of signals for the TGF¤ superfamily. Cell 85, 479-487, 1996.
Graff, J.M. Embryonic Patterning: To BMP or not to BMP, that is the question. Cell 89, 171-174, 1997.
Zhu, Y., Richardson, J.A., Parada, L.F., and Graff, J.M. Smad3 mutant mice develop metastatic colorectal cancer. Cell 94, 703-714. 1998
LeSueur, J. and Graff, J.M. Spemann organizer activity of Smad10. Development 126, 137-146, 1999
Peters, J.M., McKay, R.M., McKay, J.P., and Graff, J.M. Casein Kinase I transduces Wnt signals. Nature, 401, 345-350, 1999.
LeSueur JA, Fortuno III ES, McKay RM, and Graff JM. Smad10 is requiredfor formation of the frog nervous system. Developmental Cell 2, 771-783, 2002.
McKay RM, McKay JP, Avery L, and Graff JM. C. elegans: a model for exploring the genetics of fat storage. Developmental Cell 4, 131-142, 2003.
To access any of the publications referenced on this website please visit http://www.ncbi.nlm.nih.gov/PubMed
