 When I signed up for chemical engineering, not all my friends got it. But ever since I fell in love with chemistry in high school, it's been all about the molecules for me. Designing processes to manipulate molecules on every length scale, from huge like a chemical plant to tiny like the nanoparticles I'll be telling you about, all to address some of the big problems in the world, including human health. Cancer affects all of us, especially the ones that come back over and over again, the highly aggressive and recurrent ones, the ones that define medical treatment, even when we throw our best drugs at them. Engineering, at the molecular level, working at the smallest of scales, can provide powerful new ways of fighting the most aggressive forms of cancer. Now, these highly aggressive and recurrent tumors can occur in many kinds of cancer. High-grade ovarian cancer strikes a special chord with me because we've made very little progress in addressing the disease. It's often discovered at late stages when it's highly advanced. And after the first round of treatment, this cancer comes back for 75% of patients. At the core of these highly aggressive and recurrent tumors are genetic mutations. These cancer cells undergo changes in their genes that allow them to survive even the presence of the poisons we know as chemo drugs. These genetic mutations encode for new and unimagined modes of survival that allow them to persist even in the presence of our most aggressive drugs. For example, one gene creates a protein that sits at the cell membrane and allows the cell to pump out the molecule before it has an opportunity to take effect. The cell effectively spits out the drug. This is just one example of the many ways in which cancer can get out of chemotherapy treatment, all the result of mutant genes. Now, it turns out there is a way to turn off a gene. The key is a set of molecules known as SIRNA. SIRNA are short sequences of genetic code that guide the cell to block a gene. Each SIRNA molecule can be designed to block a specific gene inside the cancer cell, but there is a problem. SIRNA works well inside of cells, but if it gets exposed to the natural enzymes in the bloodstream or in our tissues, it degrades within seconds. It has to be packaged protected on its journey through the body to reach the cancer cell. We have to find a way to do this. Our strategy is a one-two punch to the cancer cell. First, we'll dose it with SIRNA to turn off those tumor-defense genes, then we'll give it the chemo drug to kill it, but we need a package to carry that out. Using molecular engineering, we design a nanosize package, a nanoparticle so small that it can go through the bloodstream, penetrate the tumor tissues, and get taken up by the cancer cell. We start with the nanoparticle core, a tiny capsule that contains the chemotherapy drug. This is the toxin that will ultimately end the tumor cell's life. Around it, we wrap a nanometers-thin layer of SIRNA. This is our gene blocker. Because SIRNA is strongly negatively charged, we can protect it by wrapping a positively charged polymer around it. The two molecularly charged layers stick together and create a protective layer that keeps the SIRNA from degrading in the bloodstream. Now, our bodies have a natural immune defense system. That picks out things that don't belong in the bloodstream and eliminates them. We have to disguise our nanoparticle so that it can persist in the bloodstream. So we add one more additional negatively charged layer around the nanoparticle, and now we have something that looks something like the amazing Govstopper, that candy with all the many layers of sugar on it. Now, this final layer is actually a natural, highly hydrated polysaccharide. And it actually creates an invisibility cloaking effect by creating a cloud of water molecules around the nanoparticle, allowing the nanoparticle to travel long and far enough in the bloodstream to reach the tumor tissue without getting eliminated first. Once in the tumor, the nanoparticle binds to the tumor cell and is taken up inside. Once inside the cancer cell, these nanolayers dissolve away. First, the SIRNA is released for several hours, allowing enough time to block the tumor defense genes. Then we have a cancer cell with no special defenses when the chemo drug is released, we kill it cleanly and efficiently. We've tried these systems out in animals. First, we dosed the mice contained with tumors with a nanoparticle containing the chemo therapy drug alone. It turns out that this slow tumor growth, but they still doubled over a two-week period. Then we tried our combination nanoparticle with SIRNA against the drug pump and the chemo drug, and the tumors not only stopped growing, they were regressing. The fascinating thing about this approach is that it can be personalized. You can put different SIRNA molecules in the layers to block different genes. You can introduce different drugs into the nanoparticle core. With genetics tests, we can determine which patients can benefit from this strategy. This personalized superweapon might be used to address neurological disorders, bone and wound healing, or infectious disease. Using tiny molecular engineering approaches, we can have a huge impact on human health. Thank you.