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Sanguine Manner

A better understanding of the process by which the body grows new blood vessels—known as angiogenesis—holds promise for treating a broad range of diseases. Dartmouth's multidisciplinary angiogenesis research group is optimistic about the future of the field. And the team has fun working together in the meantime.

By Laura Stephenson Carter and Sion E. Rogers

Feed me. Feed me. Feed me!" demands the man-eating plant in the Broadway musical Little Shop of Horrors.

"Feed me. Feed me. Feed me!" demands the malignant tumor—silently—in the body of a real-life cancer patient.

Both the plant and the tumor get what they want, but the tumor is more subtle in its approach. It tricks its host's body into growing new blood vessels, a process that's called angiogenesis, to keep it continuously fed with oxygen and nutrients.

Medical researchers and clinicians all over the world are discovering the secrets to controlling angiogenesis and hope to, one day, develop therapies to counteract the over- or under-stimulation of blood-vessel growth. In a healthy person, angiogenesis is a natural process whereby new blood vessels form to heal wounds, rebuild the uterine lining during a woman's menstrual cycle, or develop a circulatory system in a growing fetus.

But sometimes the body begins to build too many new blood vessels—such as in cancer, chronic and acute inflammatory diseases like rheumatoid arthritis, diabetic retinopathy, age-related macular degeneration, psoriasis, and countless other diseases. Or, in other cases, too few—such as in coronary artery disease, stroke, peripheral artery disease, and diabetic wound healing. (Some of these medical terms, plus many others in this article, are defined in a glossary in here.)

Dartmouth's Angiogenesis Research Center is led by one of the pioneers in the field—Michael Simons, M.D., who came to DHMC from Harvard in 2001 as chief of the Section of Cardiology. He brought with him a merry band of researchers and has added a few more since then. They are as apt to be teasing each other as they are to be teasing apart the mysteries of angiogenesis—but the lightheartedness is all in service of their work.

It's 9:00 a.m. on a Tuesday morning, and some 30 angiogenesis researchers have gathered in a conference room at DHMC for their weekly joint lab meeting. Each week, a different researcher presents a report on work in progress.

Before the presentation begins, people help themselves to coffee and bagels and chat noisily—about work, weekend


The members of the Angiogenesis Research Center don't just work together—they
tango, hike, and joke around together. Director Mike Simons is in red in the middle.

activities, whatever else is on their minds. The proceedings are a little late getting under way because the PowerPoint projector is misbehaving—its bulb is flickering, causing the image on the screen to pulse. Someone jokes that the machine is having a seizure. Everyone laughs.

As the presenter fiddles nervously with the projector, Nicholas Shworak, M.D., Ph.D., walks over and places his hand on it. The machine calms down until he steps away. He places his hand on it again, and it behaves. The room rocks with laughter. Finally the projector is working properly and the presenter begins. But later it fails to produce a sound effect to accompany an animation. The presenter looks rattled. "What kind of sound do you want? Beeeep, beeeep?" Shworak jokes. Everyone laughs. The young researcher visibly relaxes and continues his presentation. People start asking questions—some serious and some not.

Shworak poses some gentle, probing questions and suggests that in the future the researcher might want to present his data in a graphical format, such as a histogram or bar chart. Simons wonders about the corkscrew-shaped blood vessels on one of the slides. Often, new blood vessels grow in a screwlike configuration. "Is the corkscrew always to the right?" he asks. Simons jokes around as much as anyone, but he wants to be sure the presenter knows he really is interested in an answer. "This is a serious question," he adds.

Later, when faculty member Armin Helisch, M.D., explains that an image on the screen shows a mouse hind leg where a double ligation had been done on a blood vessel, someone jokes, "Is that double- oh-seven?"

And so the presentation continues with similar give and take—good-natured teasing mixed in with serious questions and answers.

"Very nice," Simons says at the conclusion of the presentation.


These are endothelial cells—from the lining of blood vessels—that have been treated with rPAI-123.

We're trying to understand how the vasculature grows and develops, with an idea that once you understand how blood vessels form, how they grow, you can influence the vascular process," explains Simons. "You can stimulate [angiogenesis] in

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Laura Carter has been Dartmouth Medicine's associate editor for almost six years. One of her recent initiatives was starting a formal editorial internship, in which Sion Rogers is the second incumbent. He was graduated with a degree in biochemistry and genetics from Great Britain's University of Nottingham and then spent eight months with BBC Radio before coming to the U.S. to gain some print experience with Dartmouth Medicine. All of the photographs here are the work of Jon Gilbert Fox, while the micrographs in the upper righthand corner of each spread are courtesy of members of Dartmouth's Angiogenesis Research Center.

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