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Cezar: Scientist Brings International Connections to UW Stem Cell Work

By Brian E. Clark

MADISON – Growing up in the Brazilian state of Goiana, Gabriela Cezar was deep in cattle country. And as far back as she can remember, she wanted to be a veterinarian.

“My father was head of the national beef cattle research center in Brazil, so I was always exposed to animals,” said Cezar, who earned her veterinary medicine degree in her native country and has additional graduate degrees from Scotland’s University of Edinburgh and UW-Madison.

But Cezar’s career path took a turn toward stem cell research early on. She has since worked on three continents – including a stint with the giant Pfizer pharmaceutical company. She also worked at the Roslin Institute in Scotland with the cloning team that produced “Dolly the Sheep,” an early attempt at cloning a mammal.

“Stem cells are incredibly interesting territory,” said Cezar, who joined the faculty of the animal sciences department at UW-Madison late last year. Her specialty is developmental biology.

“They have the power and the potential to lead us to many medical breakthroughs,” added Cezar. She is working with research leaders such as Jamie Thomson, who first isolated and reproduced human embryonic stem cells in 1998.

Madison biotech officials say they wish her well with her research – which focuses on toxicology and fetal development.

They are also hoping that her industry contacts in this country and abroad – as well as her business savvy - can help attract investors’ capital for local start-up companies or perhaps even lure a major drug firm here.

John McNeish, Cezar’s old boss at Pfizer and the company’s senior director of genetic technologies, has already been to Wisconsin at Cezar’s invitation.

“Of course we were sad to lose someone of her quality,” McNeish said. “But we’ve gained from the deal, too. I’ve already leveraged her move to visit Madison and make some great contacts at the university and the Wisconsin Alumni Research Foundation.”

Tom Still, president of the Wisconsin Technology Council, said Cezar brings a winning combination of international contacts and academic credibility.

“Moreover, she cares a lot about technology transfer and has said that she would like to help some of the stem cell technologies that are being built on campus get to the marketplace sooner.”

Still said Cezar’s public-speaking skills and outgoing personality will serve the academic and biotech community well.

“When you have a topic that is as controversial as human embryonic stem cell research, it’s a real asset to have someone with her scientific credentials and the ability to communicate so well.

“I don’t know if Dr. Cezar could get right-to-lifers or conservative Republican legislators to change their position, but it would benefit everyone if more people heard from Dr. Cezar.”

Mark Bugher, who directs the University Research Park on Madison’s west side, applauded her return to Madison.

“She is the prototypical entrepreneur/academician that we should be proud of,” he said. “She is brilliant and has the right kind of attitude toward technology transfer.

“We should encourage that kind of model for faculty recruitment any way we can. We should also have her out articulating the message for this campus as much as possible, too.

Because of her experience in the private sector, he said she is more credible than someone who has spent his or her life in an academic lab.

But Bugher said it may be a leap to think that she can lure a big pharmaceutical company to Madison.

“Still, her connections can’t hurt,” he said. “And the more she can talk up the area, the better it is for all.”

Bugher said he hopes her career at UW-Madison is long-lived.

“But she has concerns about the potential criminalization of human embryonic stem cell research here,” he said.

The Legislature passed a bill last year that would have outlawed some forms of stem cell research in Wisconsin. But it was vetoed by Gov. Jim Doyle.

“If that were to happen again and be signed into law, she’d be out the door from Wisconsin. I don’t think we want to chase an outstanding researcher to another state," Bugher said. “So I think the message to policy makers, particularly in our Legislature, is that if you want to be a world-class state, you have to behave like one. I hope they get that message.”

Cezar said she is flattered by the praise heaped on her and that she is pleased that she was hired to replace the recently retired Neal First, a pioneer in animal cloning and member of the National Academy of Sciences.

“It is an honor to be here,” she said modestly.

Cezar taught for a year at a veterinary medicine school in Brazil before coming to Madison to earn her doctorate. She also received a master’s degree in Brazil.

Cezar said she came to Wisconsin after she was offered a job by Mike Bishop, then head of DeForest-based Infigen – an animal science company that clones pigs, cows and sheep.

“I’d always wanted to study in the United States,” she said. “We established a collaboration in which I worked at Infigen and they funded my PhD, which I earned in the same lab I’m running now.”

Cezar also worked with Jamie Thomson while she was a graduate student. He was one of the five faculty members on her doctoral review committee.

Cezar’s work focused on an area called epigenetic reprogramming, trying to understand what it is that makes cells turn into bone, brain, liver or other tissues.

“Dolly, for example, started out as a cell from a mammary gland and it had to be reprogrammed,” she said. “In epigenetic reprogramming, you have to erase the cell’s memory so it can become other things.”

Cezar said she her specific focus was on abnormalities, which can be as high as 30 percent in cloned cattle.

“I looked at the DNA to see what was going on to see why these guys were not being reprogrammed efficiently,” she said. Cloning remains difficult and inefficient, she said, sometimes taking 300 embryos to get one animal “on the ground.”

“Still, it is very valuable if you have a bull with outstanding genetics, or have an endangered species that you want to be able to preserve,” she said.

Even before Cezar finished her studies at UW-Madison, she was recruited to work for the Pharmacia drug company in Michigan. Pharmacia was soon purchased by Pfizer and she moved to Connecticut to head a stem cell research group.

“I worked in the genetics technology group, which operated like a biotech company inside Pfizer. We were the pioneers for all of the innovative molecular biotechnology for all therapeutic areas at Pfizer.”

But her work was limited to mouse and rat embryonic stem cells, something she found limiting.

“We couldn’t use human embryonic stem cells and that is one of the reasons I wanted to come here,” said Cezar, who stayed at Pfizer for three years.

“We started generating really beautiful data with mouse embryonic stem cells that I wanted to extrapolate,” she said. “I wanted to be able to make models using human embryonic stem cells.”

“The second factor is that in a drug company, you have the responsibility to develop your work so that sometimes you operate like a production line. We had enormous room to innovate, but it had to meet the business priorities because it can cost $800 million to get a drug out.”

Finally, she said, Madison drew her back because it is a cosmopolitan city.

“There are people here from all over the world,” she said. “For someone like me, that sort of diversity is wonderful. It was not like that in southeast Connecticut. Why, there are more than 200 Brazilians in our association here.”

At UW-Madison, Cezar said she hope to have more freedom and time to work on pure research, which will make up 75 percent of her time. The remainder will be in teaching.

“This is a new science, with new applications,” she said. “I thought I would have a lot more opportunity and the time to dedicate myself to innovation. You don’t have that opportunity inside a drug company.”

She also said the chance to work with Thomson and other top stem cell scientists was a big draw.

“Absolutely,” she said. “UW-Madison has the best stem cell team anywhere. For someone who loves stem cells like I do, how could I not take this offer?”

Cezar said she was heavily recruited by several California universities. And if human embryonic stem cell research is outlawed in Wisconsin, she said she will follow those offers.

“It would be terrible for Wisconsin to lose what has been built here,” she said.

“The more I am exposed to patients and their families, the more optimistic I am that this technology will one day be able to save lives and make people healthier. If you have a dedication to your science, you can’t change careers,” she said. “This is what I love. I want to identify more opportunities for this technology. We should not tie our hands.”

Cezar said she respects the beliefs of right-to-life advocates, but does not believe a fertilized egg is a human being.

“Yes, it has that potential. There is no differentiation, no lungs, no tissues and it has not been implanted in a womb.”

But Cezar is not dwelling much on criminalization worries, she said. She is far more interested in pursuing her work, and helping attract more biotech companies to Madison.

“Whenever I see an opportunity, I act on it,” she said. “A month after I was here, I got my old boss to visit and speak about drug discovery and development and help him establish a relationship with the university and the biotech companies already here.”

Cezar also frequently travels to scientific conferences, which often are populated by investors looking for deals.

“I will try to interest these people in visiting Madison,” she said. “It’s already working. An investment group from Philadelphia is making plans to come here to visit the research park and talk to WARF. E-mails are being traded every day. I know of another group from San Francisco that’s interested.”

If she were a venture capitalist, Cezar said she’d put her money here.

“I would think this is the best place to invest if you are interested in stem cells,” she said. “And while scientists know of Madison’s reputation, we need to do more to sell this area to others in the general public.”

She said investors know of WARF and its intellectual portfolio, but many are unaware of the university’s current stem cell research program.

She said she recently set a venture capitalist straight when he told her of the prowess of Harvard, MIT and academic institutions in London.

“He did not know of our strengths,” she said, frowning. “But he will likely be here in February. Our science has is moving forward. We are learning how stem cells can be a vehicle to get drugs into the brain. And one of our faculty was awarded a huge grant recently dealing with multiple sclerosis. We continue to lead.”

But Cezar said she also knows the importance of managing patients’ expectations because cures for Parkinson’s and other diseases - or successful stem cell treatments for spinal cord injuries - may be years away.

“Many of us have someone in our families who could benefit from stem cell therapy in the future, but the technology is not ready now and families need to understand that,” she said.

In the meantime, she will focus on in vitro predictive toxicology, using human embryonic stem cells to learn – among other things – how chemicals in the environment affect development and perhaps cause birth defects.

She is also now writing a grant to learn develop an in vitro model for autism.

“As a scientist, I am very interested in why cognitive disorders in children are increasing so much,” she said.

“Is it external factors like exposure to mercury that are causing changes in gene expression?” she asked. “Perhaps through studies using human embryonic stem cells, we can unlock that and other puzzles.”

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