LA JOLLA, Calif., February 12, 2010 - An international team of investigators at Sanford-Burnham Medical Research Institute (Sanford-Burnham, formerly Burnham Institute for Medical Research), Nijmegen Centre for Molecular Life Sciences and other organizations have discovered that TKS4, a protein implicated in cancer metastasis, also plays a significant role in Frank-Ter Haar syndrome (FTHS), a rare fatal disorder. The research was published on February 12 in the American Journal of Human Genetics.
Children with FTHS suffer from skeletal, cardiovascular and eye abnormalities and usually die in infancy or early childhood. Hans von Bokhoven, Ph.D., at Nijmegen, with assistance from clinical colleagues in several different countries, studied 12 families who had been affected by FTHS. The team mapped the condition in 7 of these families to a mutated SH3PXD2B gene, which normally contains the code to create the TKS4 protein. Dr. von Bokhoven then began collaborating with Sara A. Courtneidge, Ph.D., at Sanford-Burnham, who had been studying the relationship between TKS4 and invadopodia, cellular protrusions that facilitate cancer cell migration and invasion. The Courtneidge group, together with Sanford-Burnham researchers José Luis Millán, Ph.D., and Pilar Ruiz-Lozano, Ph.D., and researchers at University of California, San Diego, determined that mice without TKS4 showed virtually identical traits to FTHS patients, confirming the results of the gene mapping. Interestingly, one FTHS family with a normal SH3PXD2B gene was nevertheless deficient in TKS4, indicating a consistent mechanism for the disease.
"This research illustrates the importance of collaboration in the scientific discovery process, and how the study of one disease, in this case cancer, can have a profound impact on the understanding on another." said Dr. Courtneidge, "In the future, we hope to use our mouse model to study the disease in more depth, as well as to determine whether other genes involved in invadopodia formation are also associated with FTHS."
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute (formerly Burnham Institute for Medical Research) is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Sanford-Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top independent research institutions nationally for NIH grant funding and among the top organizations worldwide for its research impact. From 1999 - 2009, Sanford-Burnham ranked #1 worldwide among all types of organizations in the fields of biology and biochemistry for the impact of its research publications, defined by citations per publication, according to the Institute for Scientific Information. According to government statistics, Sanford-Burnham ranks #2 nationally among all organizations in capital efficiency of generating patents, defined by the number of patents issued per grant dollars awarded.
Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a nonprofit public benefit corporation. For more information, please visit www.sanfordburnham.org.