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Sanguine Manner


meetings are meant for constructive criticism; they help keep everyone informed about each other's work. "It's good to be exposed to [other people's projects], both in order to expand my horizons [and to] not be completely channeled or confined in the walls of my own projects," he says.

Researchers were exposed recently to the details of Horowitz's work when he gave a presentation at a vascular biology seminar. This weekly seminar, held every Thursday afternoon, is another forum where researchers can practice their public-speaking skills and share ideas. Sometimes researchers lecture on journal articles and other times principal investigators present their own results when they're getting ready to submit a paper for publication. The tone of these meetings is more subdued than that of the joint lab meetings.

At the joint lab meetings, "the idea is to try to present unpolished, primary data. Then you can critique and evaluate it," says Kiflai Bein, Ph.D., who is investigating the molecular basis of blood cells growing under laboratory conditions. The vascular biology seminar "is supposed to be more for polished studies," he continues. "So when you share it with your colleagues, they serve as the primary critics. This is important, because if, for instance, they don't understand what I'm trying to say, then I can't expect much from outside reviewers."

Mary Jo Mulligan-Kehoe, Ph.D., a cancer researcher, not only understood what Horowitz was trying to say, but she was almost giddy with excitement. Horowitz had explained something that was relevant to her own research with a PAI-1 protein that inhibits angiogenesis in vivo for breast cancer. "We've been battling with the signaling cascades that are occurring as a result of endothelial cells being stimulated with my recombinant PAI-1 protein," she says. "But all of a sudden you're sitting there listening to this, and lights come on. . . . I had thought we were doing something to FGF. But it's really going through a different receptor."

With all the investigators concentrating on different aspects of the vascular process, and being so willing to share their knowledge, people are bound to learn from one another.

These are mouse endothelial cells that have been stained for actin (blue), FGF (green), and FRS2 (red).

"It's like a moving kind of conglomerate. It's hard to explain the dynamic interactions which occur," says Armin Helisch, who is interested in the mechanisms of arteriogenesis, the growth of collateral arteries as opposed to capillaries. "I think it's inspiring because by people [being] in the different orientations, we can all learn from each other, expand our horizons, which is better than if everyone only thinks the same thoughts—as was somewhat true in my prior lab, where everything was only collateral growth with a certain focus."

It is to Simons's credit that he even recruited Helisch to join the Angiogenesis Research Center in the first place. Simons believes that new blood vessels form when endothelial cells migrate to an area in response to signals from damaged tissue. But Helisch argues that there are already preexisting blood vessels that remain invisible until they are needed. They are then called into action when a nearby vessel is blocked and the surrounding tissue needs an alternate blood supply.

Helisch, an echocardiologist who spends part of his time seeing patients, jokes that he only became a researcher because the angel of research kissed him one day. Then he turns serious as he explains that angiogenesis scientists assumed that new blood vessels were being created in areas injured by cardiovascular disease, because a number of new capillaries formed. "It was kind of a shortcutthinking approach that this is directly related," he says. "Because physiologically—if a big vessel is occluded—it doesn't really make

any sense to assume that small capillaries, in the distal leg, for example, in humans or in an animal hind limb, would be able to have any effect on this restoration of perfusion."

Helisch and Simons aren't shy about disagreeing with one another in public. Once, at a joint lab meeting, Helisch inadvertently says something about collateral vessels having been formed.

Simons pounces. "Did you notice that he used the word collateral formed?" he asks gleefully. Everyone laughs. "Someone should mark the calendar," Simons teases.

Helisch is caught off guard but recovers quickly. "Even in arteriogenesis, vessels form based on preexisting collaterals," he insists. All the disagreements are in the same vein—cheerfully competitive and friendly.

"We are a very collegial group, both in the workplace and out of the workplace," says Shworak. "We have a lot of [joint] outside activities. We have an occasional ski day, group barbecues in the summer. Mary Jo had a St. Patrick's Day party at her place."

Participants in the center also enjoy hiking and doing other activities together. Several take weekly tango lessons together. Helisch even tried to recruit a couple of Dartmouth Medicine staffers to come to a tango workshop.

"These social aspects oil the wheels of the research," says Horowitz solemnly. "They help it function easier. When things don't go well socially, or when there are tensions, people spend mental energy on this, and that always detracts from the research itself."

The socializing seems to work because the members of the group clearly expend plenty of energy on their research.

The projects are fascinating. Take Kiflai Bein, who coaxes endothelial cells to grow into blood vessels in culture dishes. The cells will form tubes like plant roots, as long as they are embedded in a fibrinogen matrix. Just as plant roots grow toward water, laboratory-bred blood vessels grow toward other vessels in response to chemical signals, explains Bein. Put two such matrixes side by side


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