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X. Nancy Xu, the Old Dominion University chemist and biochemist, has won a $1.25 million grant (R01) from the National Institutes of Health (NIH) that underscores her growing international reputation in nanobiotechnology.

In the summer of 2005 she received an award of $1.3 million from the National Science Foundation for fundamental cellular studies at the nanoscale, which ranges from one-billionth to one-millionth of a meter.

Now, less than a year later, the NIH has chosen Xu to do single-cell and nano-probe research that sometime in the not too distant future could lead to more efficient gene therapy and to other revolutionary medical treatments for diseases such as cancer.

"She is a very gifted and talented scientist who has demonstrated an extraordinary ability to garner the sort of high-level, competed funding that raises the national stature of a research university," Richard V. Gregory, dean of ODU's College of Sciences, said of Xu.

"Because of this type of funding, ODU is being recognized as an emerging leader in nanoscience, and we look forward to continued growth in the field under the leadership of Nancy and her colleagues," Gregory added.

An associate professor, Xu said she is especially pleased with the award, given the recent NIH budget paring. "This is a confirmation of the importance of our research program, and I certainly look forward to getting more exciting research projects done. I am extremely proud of my past and present students and postdocs for their significant contribution to the research program. We share the common goal of advancing scientific research, and we all work very hard to achieve our goal," she said.

Simultaneous with the announcement of the NIH grant was the publication of a National Cancer Institute (NCI) article highlighting Xu's work (http://nano.cancer.gov/news_center/monthly_feature_2006_may.asp). The article, prepared by the NCI Alliance for Nanotechnology in Cancer, is titled "Mission to the Inside of a Living Cell." It emphasizes the importance to cancer research of nanotechniques Xu has developed for probes of living cells. Most past and current research findings about biochemical reactions in cells come from tests of dead cells or of purified biomolecules extracted from cells. The "rate of a biochemical reaction occurring in a test tube could be quite different from that observed for the same reaction inside a cell," the article states.

In recent years, Xu and her research group at ODU have been prominent creators of nanoparticles that can enter a cell and literally "light up" the interior. The NCI article gives high marks to her silver nanoparticles, which are exceedingly bright and do not photo-decompose, surpassing any other available probes for cellular imaging.

These silver nanoparticles, according to the article, promise to provide detailed information (via advanced microscopes) about the biological processes and dynamics in living cells. This information can be used to (1) identify changes that occur when cells undergo malignant transformation, (2) perform single-cell cancer tests, and (3) provide exceedingly early cancer detection that could bring major improvements to cancer therapies.

"The primary challenge now is to develop methods for modifying the surface of the nanoparticles to make them more biocompatible, so that more biological processes can be observed without perturbing or destroying the cell's intrinsic biochemical machinery," Xu is quoted as saying in the NCI article.

The NIH award, which provides research funding over five years, will allow extensive nanoparticle research by Xu and her two chief collaborators, Christopher Osgood, ODU associate professor of biological sciences, and Jean-Michel Jault, a researcher at France's Commissariat a l'Energie Atomique. The researchers will develop optimal nanoparticle probes to study the molecular mechanism of a transporter that is primarily responsible for multi-drug resistance in cancer therapy. The research also will involve the use of nanoparticles as carriers for effective drug delivery.

Osgood, a veteran researcher who directs ODU's Ph.D. program in biomedical sciences and has worked with Xu on previous projects, was lavish in his praise of the young, Chinese born scientist. "She is nearly unique in having simultaneous support from both NSF and NIH," he said. Both funding agencies are typically supporting the top 10-15 percent of applications. To receive million-dollar awards from both is a spectacular achievement and an indication of the high regard for Dr. Xu's work and her research team."

The research will focus on ATP-binding cassette (ABC) transporters that are present in bacteria cells, as well as in human cells. These transporters are membrane proteins that serve, in layman's terms, as cellular gatekeepers and bouncers. Of particular importance to medical science is the transport mechanism by which intruding specks-such as nanoparticle probes or molecules of antibiotics and cancer-fighting medicine-are recognized and expelled from cells. Although the transport mechanism is a natural protective measure, it works against physicians trying to eliminate sick cells. It "bounces" probes or medicines that are sent into cells to arrest an infection or malignant growth.

With more study, the day may come when chemotherapies, for example, could have stealth qualities. Molecules of medicine would be able to enter cells and avoid the ABC transporters long enough to perform their mission. This would allow precise targeting of cancer cells and avoid the current massive doses of medicines needed to outgun the transporters. The massive doses kill healthy as well as diseased cells and are what cause the sicknesses and severe symptoms that accompany chemotherapy, the so-called side effects.

Better knowledge of intercellular activity also may bring advances in gene therapies, in which one or more genes are introduced into a cell for the treatment or prevention of disease.

Xu said in an interview that she foresees "profound" advances in medicine and many other fields based upon nanoscience and nanotechnology. "It is truly interdisciplinary. Every scientist and engineer can make significant contribution to his or her own field using nanoscience and nanotechnology. There is no doubt that nanoscience and nanotechnology will play a vital role in advancing every scientific discipline and major breakthroughs will take place in this exciting, emerging new field."

She said she believes any university that aspires to be a recognized as a research institution in the U.S. must choose nanoscience and nanotechnology as a major research focus. "It is crystal clear that no institution can become a leader in science and engineering without a distinguished nano program."

Through her research projects and several grants, Xu has become known on the ODU campus as a standard-bearer for nanoscience and nanotechnology. She has presented research and chaired symposia at conferences throughout the world.

Her dream is to help grow nano-research at ODU to the point that its various projects are integrated into one initiative and conducted under the auspices of one discrete, well-funded center and in a state-of-the-art nano-facility. She already has her eye on advanced instrumentation, such as a $2 million high-resolution transmission electron microscope and $1 million nano-fabrication apparatus, which she needs for her ever more sophisticated analysis.

"To make this dream come true, it will require substantial institution support, and I certainly cannot do it alone," she said.

Currently, she is able to use the services of most of the advanced nano-facilities around the nation for her research program via National Nanotechnology Infrastructure Network (http://www.nnin.org/).

Xu is the sole principal investigator on the NIH award. She sees the NIH award as a sort of an indicator showing the passage from young investigator to established investigator. As a young investigator, she said, one might get "favored considerations." For this NIH R01 grant, however, she had to compete alone, and without special considerations, against a full field of seasoned investigators through the most rigorous review process conducted by a NIH panel of 20-30
experts in the field.

This article was posted on: June 15, 2006

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