This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Mucormycosis is a life-threatening infection that occurs in patients whose immune systems ar enot working properly. Unfortunately, these patients are increasingly common, and therefore the frequency of mucormycosis is rising. Despite aggressive treatment, which includes disfiguring surgery, more than 50% of patients with mucormycosis die. Clearly new strategies to prevent and treat mucormycosis are urgently needed. The most common cause of mucormycosis is the fungus, Rhizopus oryzae. Patients with too much iron in the blood have a higher risk of infection caused by this organism. We have found that R. Oryzae damage to human cells in the test tube is dependent on iron. Additionally, we have cloned a gene from the fungus that allows it to grab and ingest iron even in iron-rare conditions. Our current research plan is to better understand how iron impacts the ability of the fungus to injure human cells. We also plan to create a mutant of the fungus that cannot take up iron to confirm that this mutant causes less damage to human cells. This will prove the role of iron in allowing the fungus to cause infection. To perform these experiments, it is necessary to grow in the test tube the same type of human cells that the fungus normally attacks. A classic feature of mucormycosis infections is the tendency of the fungus to invade blood vessels, where iron-rich blood is found. During this invasion, the fungus must grab hold of and penetrate through the cells that line the blood vessel wall, called endothelial cells. Therefore, it is necessary to grow endothelial cells in the test tube. The most available, richest source of endothelial cells are the umbilical cord veins. The umbilical cords are anonymously removed from placentas that are to be discarded after delivery. There is no link between the patient and the umbilical cord that would allow the patient's identity to be known. Given the absence of any link between the umbilical cord, the fact that the umbilical cords are anonymously removed from the placenta after delivery of the child, the fact that the umbilical cords would be destroyed if they were not used for this research, the risk to the patient is minimal. Given the potential for discoveries to be made that could lead to a vaccine to prevent common and life-threatening Rhizopus infections, the potential benefit of this research is high. Therefore, the risk:benefit ratio is highly favorable.
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