Marfan Syndrome (MFS) is a genetic disorder that affects more than 7,500 Californians. Patients develop severe complications, affecting several parts of the body (eyes, limbs, aorta). During the last two years, we have used the funds from this grant to develop new cell lines aimed at studying MFS in a dish. These cell lines, are called pluripotent stem cells, and have been generated from: (i) an embryo that was donated for research and was known to have inherited the MFS disease (these cell lines are named human embryonic stem cells (hESCs)); and (ii) from skin biopsies of adult patients (these cell lines are named induced pluripotent stem cells (iPSCs)). These stem cell lines allow us to study MFS by differentiating the cells to adult cells (mainly bone and cardiovascular cells) and not other random adult cells. Using these new stem cell lines, we can test whether hESCs and iPSCs are functionally the same, by comparing them after we make them become cardiovascular and bone cells. We have observed that when the cells form bone or muscle cells, the stem cells with MFS are different and do not behave the same as those made with normal stem cells. We also started to use reagents that can force MFS cells to resemble and behave like normal bone cells. This is called “rescuing the disease phenotype”. For the first time, we are close to describing a stem cell-based technology not only to understand the mechanism(s) of the MFS but also to develop a screen for new drugs to treat people with MFS. However, we still need to confirm our results by repeating the experiments. Our results are very promising for understanding the bone issues in MFS, but continued efforts are also required to understand the cardiovascular issue. It is important to point out that the most important health risk associated with the disease is an aortic aneurysm that, if untreated, leads to death around 35 years old. In conclusion, we are continuing to generate data that will provide the foundation for improving our knowledge of the disease, and also will potentially assist us in developing new therapies for improving MFS patient lives.