College of Science Magazine, Fall 2005 - Physics - Virginia Tech

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College of Science Magazine Issue No.1 Fall 2005 Call it coincidence. Call it destiny. Call it good fortune. Whatever it was, when two young scientists met at new faculty orientation at Virginia Tech in 1992, it was the start of something great. In the 13 years since then, Karen Brewer, professor of chemistry, and Brenda Winkel, professor of biology, have led research teams that have developed new and potentially revolutionary ways of treating cancer in humans. A plant biologist and inorganic chemist working side-byside? It seemed an unlikely union, but when a graduate student in chemistry that same year expressed an interest in taking a biological focus in his research, the deal was sealed. Chemical and biological researchers team up to develop new light-activated cancer therapies Light absorbing unit Active sites their work focused on the other drawback with Cisplatin – that tumors can become resistant to the drug. And that’s where the beauty of having a biologist and chemist working closely together really started to show. While Winkel’s team worked on DNA interactions, Brewer’s team was busy modifying the chemical structures of the drug. Employing basic techniques that are routinely used in Winkel’s lab, doctoral student Matt Milkevitch was able to develop an assay for DNA binding activity that has now become standardized in other chemical biology labs. The team was eventually able to change the shape and basic properties of the drug molecule, thus making it unrecognizable to the tumor. Metal-based systems for delivering pharmaceuticals are a popular area of research. One reason is that metals are constantly interacting with their environments, thus their properties and reactivity can easily be changed. Metals are also advantageous because they can be made into highly colored dyes and by doing so are more easily detected. Using colored systems also helps with the team’s research into light-activated therapy. Bridge units Light absorbing unit Light Shedding across Disciplines New Molecular Structures The research team started by looking at ways to overcome some of the inherent drawbacks in the widely used cancer drug Cisplatin. One such drawback is that the drug does not dissolve well in water. This means it must be crushed and administered in suspension form, which can cause significant kidney damage. So the first thing the research team did was develop a system that would dissolve in water. Once they did that, College of Science Magazine Issue No.1 Fall 2005
College of Science Magazine Issue No.1 Fall 2005 Photoinitiation One of the ways of decreasing the harsh side effects of chemotherapy is to deliver the therapy only to cancerous cells, thus maintaining the integrity of surrounding healthy tissue. Currently, one method that is fairly effective at more precisely targeting cancerous cells utilizes light-activated therapy. The patient (for example, one with esophageal cancer) takes the drug in pill form. It remains inert until a fiber optic bundle of light shines into the esophagus, which then activates the drug only at the location of the cancerous cells. Foundation funding to the tune of $300,000 for three years and is capturing the attention of research partners at other institutions across the country. BEFORE This is a promising therapeutic technique, but it has a few inherent problems. The main one is that because the light energy is transferred to oxygen, it is actually the oxygen that kills the cancerous cells. This treatment method is not highly effective in aggressive tumors because they are already depleted of oxygen due to their rapid replication. Vero cells. Area of light exposure in red. “I am most surprised by what you can accomplish when you use this type of team approach” AFTER TREATMENT Research assistant Matthew Mongelli tests one of the luminescent samples. Photo by Michael Kiernan. Collaborative Benefits The collaborative spirit of this project has made its way throughout the chemistry and biology departments as Brewer and Winkel agree that the collaborative effort on well. Each department is receptive to hosting presentations this research has been remarkable. by the other, and Brewer and Winkel are able to serve as “This is what really sets our research apart from what you see co-advisors to students involved in their research, not always an easy administrative hoop to jump going on at medical schools,” Winkel said. “Rather than the through. “We decided to come up with some molecular systems that didn’t require oxygen, but would still be light- activated,” Brewer said. The therapy the research group has been developing utilizes a wavelength of light called the therapeutic window, which is neither absorbed nor reflected away by tissue. This is the same wavelength that one sees as red light shining through a hand covering a flashlight. By using light at this wavelength, the research team believes they can signal their manmade molecules to release cancerfighting agents at the disease site. The research team recently started a partnership with Theralase Technologies Inc. to design molecular systems that use light that is in the therapeutic window. Brewer and a former postdoctoral fellow, Shawn Swavey, co-hold a patent, licenses to Theralase, in this new technology. The project has received National Science Dead Vero cells Live Vero cells trial and error of what works and what doesn’t, we are much more methodical so we can understand the mechanism and why things work or don’t work.” The Brewer and Winkel research effort is a classic example of the way the process of university research benefits students as well as researchers. Over the past 13 years, more than 50 students have been involved in the research. “With the student involvement, the project has really taken on a life of its own,” Winkel said. “They bring their own ideas and their own talents. They’re the ones who make valuable mistakes that lead us in new directions.” It is clear that Brewer and Winkel are in this project together as much for the students as for the pure research. “I never cease to be amazed by our students at Virginia Tech,” Brewer said. “We get some incredibly talented, motivated, energetic students, and if we challenge them, they really do step up to the plate. We’re willing to do what’s right for their intellectual development.” For these two talented, dedicated scientists who have spent over a decade testing and re-testing hypotheses in the world of pharmaceuticals, professional life has been full of surprises. But what has been their biggest source of wonder? “I am most surprised by what you can accomplish when you use this type of team approach,” Brewer said. Winkel agrees. “This partnership has been one of the most productive learning environments that I’ve ever been part of.” College of Science Magazine Issue No.1 Fall 2005
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College of Science Magazine, Fall 2005 - Physics - Virginia Tech

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