Research Reveals How Antiestrogens Save Bones

or many years doctors have prescribed the hormone estrogen to postmenopausal women to prevent osteoporosis. But estrogen may also make women more susceptible to breast cancer and seems to accelerate the growth of existing cancers. To provide women the benefits of estrogen therapy without the risks, and to enable breast cancer patients to continue to safeguard their bones without reducing their odds of survival, a number of companies make drugs known as partial antiestrogens, which prevent bone loss without promoting cancer.

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From left, UMass researchers Gary Stein and Jane Lian with Christopher Lengner.

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Until recently, it wasn't clear how antiestrogens affect bone tissue or how their benefits compare with estrogen. Research by Christopher J. Lengner '98 is helping to answer those questions. For his Major Qualifying Project in biology, Lengner studied the effects of estrogen and several antiestrogens on cultures of bone tissue. Working in the laboratory of Gary Stein, deputy director for basic research at the University of Massachusetts Medical Center, Lengner exposed bone tissue from rats to various doses of each compound. He then watched to see how the drugs affected the production of proteins that promote the growth of osteoblasts (cells responsible for the maturing, mineralization and hardening of bone) and osteoclasts (cells that eat away at bone).

"Maintaining healthy bones requires a fine balance between the actions of these two cell types," Lengner says. "If there are too many osteoblasts, bones become overgrown; too many osteoclasts, and bones deteriorate. Estrogen prevents bone loss by promoting the growth of osteoblasts more than osteoclasts. We found that antiestrogens promote osteoblast growth, but also retard the growth of osteoclasts. In this way, they actually have a more beneficial effect on bones."

Lengner says his research also revealed that antiestrogens boost the levels of the osteoblast-promoting proteins during the period of programmed cell death, a time when bone cells normally don't produce many proteins. "The results indicate that these drugs are capable of not only helping bones grow stronger, but of ensuring that bones remain strong even after the period of growth has ended."

"Chris is working on a small but vital piece of a puzzle we feel we are close to solving," says Jane Lian, professor of cell biology at UMass Medical Center, who is co-advisor for the project with Jill Rulfs, associate professor of biology and biotechnology at WPI. "It's rare for an undergraduate to have the opportunity and the skill to complete this type of research. We expect his findings to be a significant contribution to our understanding of how to keep postmenopausal breast cancer survivors alive and healthy for many years after diagnosis."

Bonnie Gelbwasser

Where the Wild Things Are

eterinary professionals who work with cats and dogs can find a wealth of clinical data readily available to help them assess their patients' status. Until recently, similar information about such denizens of the forest or fields as the black-footed ferret, the American black bear, the eastern screech owl or the American kestrel was harder to come by. A Major Qualifying Project by a WPI student has changed all that.

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Thomas Jenei and his wildlife database.

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"Little data is available on these species because they are seen less often - and in smaller numbers - by animal experts," says Thomas Jenei '99, who worked with Mark Pokras, D.V.M., of the Tufts University School of Veterinary Medicine to develop a wildlife database for the World Wide Web (www.vec.tufts.edu/rehab/index.html). The database contains information about blood counts, serum chemistry, temperature, pulse, respiration and average adult weights for 33 species. Jenei surveyed veterinarians and wildlife rehabilitators to guide the development of the site.

"There is a large database for captive zoo animals, called ISIS/MedArks, but ours is the first database for free-ranging wild animals," Pokras says. "It's a valuable contribution to the care of these birds and mammals, and has been well-received by wildlife rehabilitators and others involved in wild animal care."

Jenei, a biology major, is enrolled in WPI's joint degree program with Tufts, and will continue on to the Tufts veterinary school in the fall to complete his D.V.M. degree. He and Pokras say both Tufts and WPI intend to expand on the database project next year.

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Project Makes an Art of High Technology

n innovative scanner developed through a partnership between WPI and the Worcester Art Museum will enable museums and galleries to see what lies beneath the surface of their art treasures. The low-cost imaging device makes the benefits of digital imaging, previously possible only with expensive technology, available to virtually any art historian, curator, gallery owner or collector.

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From left, Pat Noonan and Scott Townsend with Worcester Art Museum Chief Conservator Lawrence Becker.

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The scanner illuminates an artwork with light in the visible, near-infrared and ultraviolet spectra. Minerals in paint pigments react differently to light of different wavelengths, so variations in the intensity of the reflected light can reveal details about what lies beneath the surface layers of paint and dirt. It was developed by Patrick Noonan '98 and Scott Townsend '98, who modified a document scanner by adding controlling circuitry and a source of near-infrared light. They also wrote software that allows the device to be controlled with a personal computer.

The prototype the students built uses only visible and near-infrared light; they hope the ability to scan in ultraviolet wavelengths will be added to future models. The device can scan an 8-inch by 10-inch area and must be placed close to a painting to obtain an accurate image, making it suitable for scanning small works or portions of large paintings. The students developed specifications for a full-scale model.

Noonan and Townsend worked with Chief Conservator Lawrence Becker, Paintings Conservator Rita Albertson and Paper Consevator Joan Wright at the art museum to learn more about how museums use imaging devices; Becker and Albertson also helped with the design and testing. The project was advised by Richard Vaz '79, associate professor of electrical and computer engineering, John McNeill, assistant professor of electrical and computer engineering, and Fabio Carrera '84, adjunct instructor. Carrera, a native of Venice, and Vaz are co-directors of WPI's Venice Project Center, where the definition of the project began about three years ago when Carrera learned that Paolo Spezzani, a world-renowned art historian and curator based in Venice, was interested in an affordable scanner.

"Pat and Scott started with inexpensive, off-the-shelf technology, then applied just the right amount of intelligent engineering," McNeill says. "The result is an affordable, easy-to-use system that meets the immediate needs of a wide range of customers. They've also identified the issues that need to be addressed to scale up the concept to image large-scale works of art, such as murals and frescoes. This MQP is a great example of engineers working to understand what customers need and then designing a solution."

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Student Sleuths Use Science to Solve the Mystery of the Statue

hree WPI undergraduates are using computers and materials science to solve a 70-year-old-mystery for the Worcester Art Museum. The puzzle revolves around an ancient terra-cotta statue the museum purchased in the 1920s. Depicting a mourning woman, it once sat atop a tomb in Canosa, a region in Southern Italy that was then colonized by Greeks.

The 3-foot-tall statue - believed to be one of about 15 extant in the world - broke into several pieces during its journey to Worcester. It was placed in storage, awaiting repair, and was not seen again until 1996, when Lawrence Becker, the museum's chief conservator, discovered it in a back room.

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"There are major differences between how curators examine art materials now and how they learned about their history in the past... Now we recognize the importance of not damaging the object."
Christopher Coté 99

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When Karen Rutledge, assistant professor of chemical engineering at WPI, learned about the statue, she wondered whether modern materials science might provide some answers about its origin, composition, function and symbolism. She organized two student projects to get some answers.

For their Interactive Qualifying Project, Christopher Coté '99 and Leslie Valentine '98 looked into the statue's history and examined the feasibility of using nondestructive evaluation - using equipment at the museum or the capabilities of WPI's Materials Characterization Laboratory - to reveal some of the object's secrets. In the process, they learned how the job of museum curator has changed over the years.

"There are major differences between how curators examine art materials now and how they learned about their history in the past," Coté says. "A hundred years ago, people didn't care what they did; they would break off pieces to see what the materials were. Now we recognize the importance of not damaging the object."

Lisa Angle '99 used such materials science tools as x-ray defraction and scanning electron microscopy to examine bits of terra-cotta and paint from various parts of the statue. She was particularly interested in the chemical makeup of the pink-toned pigment on the hands and feet and the white "slip" that coats the entire figure, and in determining whether the paint - and even some of the clay - was added after the statue was created.

"Having the statue in pieces is an advantage," she says. "In some cases, you can see where the statue had been pieced together and whether someone slapped on some adhesive or glue."

The museum hopes to bring the statue back to its original appearance - a project expected to take several years.

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