Researcher teams receive $200k for medical studies

By
Monday, March 9, 2009

Two research teams with collaborators from the Warren Alpert Medical School and the Women and Infants Hospital of Rhode Island have received grants to study fertility and pregnancy risks.

Funded by the Rhode Island Science and Technology Advisory Council, the grants are designed to encourage collaborative research and development within the state, according to the hospital’s Feb. 23 press release.

This year, the council awarded grants to seven Rhode Island teams working in a variety of fields. Each team received approximately $200,000 in research funding.

One team – a collaboration between Associate Professor of Medical Science and Engineering Jeffrey Morgan, Professor of Obstetrics and Gynecology Sandra Carson and Assistant Professor of Engineering Anubhav Tripathi – will use a 3-D Petri dish technology previously developed by Morgan and colleagues to create an “artificial ovary” that could be used to preserve the fertility of women undergoing certain medical treatments.

Carson, who directs the Division of Reproductive Endocrinology and Infertility and the Center for Reproduction and Infertility at Women and Infants, said she represents “the human side” of the research. She said Brown already has a program to freeze ovarian tissue and eggs for women about to undergo chemotherapy or radiation. The problem, Carson said, is that sometimes women must wait for weeks before the tissue and eggs can be harvested, which can present problems for their medical treatment.

The artificial ovary could replicate egg maturation so eggs could be harvested from women earlier to facilitate in vitro fertilization.

“We’re trying to create that three-dimensional structure to mature the egg to a point where it would be suitable for IVF,” Morgan said, though he added that the eggs used in the research and development phase will never be fertilized and implanted.

While the artificial ovary is the immediate clinical goal of the research, Carson said it would also help increase understanding of the way eggs are nourished. “We hope to be able to investigate a number of physiological processes we don’t understand,” she said, including the way the cell layers in the ovary interact with each other and with egg cells.

Morgan’s team uses a computerized model to synthesize an agarose gel to create spheres of cells. “We can take those spheres and put them into a second mold, and those spheres will fuse and form a larger, more complicated tissue,” he said. In a paper published March 1, Morgan and graduate students showed that these “building blocks” could form tissues that mimic vasculature.

The development of the 3-D Petri dish to grow tissues and “create an environment where cells stick together” was first introduced by Morgan’s team in a paper published in 2007.

Understanding the principles behind cell adhesion is relevant to developmental biology and basic cell biology, Morgan said, adding that it may also shed light on some of the processes involved in cancerous cell development, during which cell adhesion can go wrong. “We see it as a very fundamental process,” he said.

Because his work may reduce the need for animal models, Morgan has received funding for the 3-D Petri dish from the International Foundation for Ethical Research. The reasons for the “worldwide movement” to eliminate animal testing are primarily ethical, but they also have practical consequences: “It costs less,” he said.

“What the industry needs are in vitro models that mimic selected tissues within the body,” Morgan said. “That way they can test more drugs cheaper and more thoroughly.”

Carson said her team had been working together for “a little over a year.”

“It’s terrific,” she said. “We all sort of bring our own piece to the puzzle.”

The team has already developed an artificial ovary model that they hope to bring to the clinic soon, Carson said.

Another group in the obstetrical field to receive the STAC grant is studying complications in pregnancy. The team, headed by Professor of Pediatrics Surendra Sharma, also includes Professor of Pediatrics James Padbury, pediatrician-in-chief at WIHRI, Zahir Shaikh, professor of pharmacy and toxicology at the University of Rhode Island and Udo Markert, a researcher at Germany’s University of Jena.

The team is investigating proteins involved in the development of preeclampsia, a pregnancy complication characterized by high blood pressure and excretion of protein in the urine. Sharma said preeclampsia affects 10 to 15 percent of women and is related to maternal and fetal morbidity and mortality.

Still, Sharma said, “despite extensive investigations, it has remained enigmatic, and there is no treatment.” Part of the problem, he said, is that development of preeclampsia is difficult to predict and does not occur until the third trimester when “we can’t do much about it.”

He hopes his team’s research can change that. By comparing serum samples of pregnant women who went on to develop preeclampsia to those who did not, Sharma and his team identified a protein that women with preeclampsia lack.

Sharma and his colleagues have since developed an in vitro test for the protein, which has allowed them to predict early in a woman’s pregnancy whether she will develop preeclampsia.

The team has also demonstrated that injecting this protein into animal models prevents them from developing the disorder. In mice, “one injection can rescue a pregnancy,” Sharma said.

He expects the grant to help his team continue to develop the research so that it can win Food and Drug Administration approval for use in humans.

Sharma – who led another team that also won a grant from STAC last year to study proteins associated with placental inflammation – said he was “very proud” to have won a grant two years in a row.

He has high hopes that his research will soon be applied in clinics.

“We have completed a great deal of work already,” he said. “And so far, so good.”