Estela Jacinto, a scientist in pursuit of new ways to treat cancer

This feature is part of "I Am New Jersey," a Star-Ledger series profiling some of the people who make the Garden State special.

When Estela Jacinto, an associate professor at Robert Wood Johnson Medical School, lectures to her students on the biology of disease, she talks about the complexities involved in cell growth, how chromosomes may develop mysterious kinks and proteins can sometimes cause cells to go haywire. The damage that sets a disease in motion, Jacinto knows, can be caused by so many things ? a flash of radiation, an exposure to chemicals, a bout with a virus.

The day after giving one of those familiar lectures last month, Jacinto?s 10-year-old daughter was diagnosed with acute lymphocytic leukemia, and the mother of two found herself tormented by the same questions she has discussed so often as a scientist.

"I tried to think how could I have damaged her genome," Jacinto says, her voice growing softer. "I know as a kid she had a flu a couple of times, but was that enough to cause leukemia? It?s mind-boggling when you think about all of the things that can go wrong."

Jacinto, a native of the Philippines with dark eyes and an easy smile, has spent more than a decade studying how normal cells grow and what causes the process to go wrong and allows cancer cells to proliferate.

Much of her research has focused around the activities of the TOR protein, which plays an important role in regulating cell growth. (The protein is the target of the immunosuppressant drug rapamycin resulting in its acronym of a name. When it appears as mTOR, it refers to mammalian cells.)

Jacinto?s efforts in the laboratory resulted in the discovery of a set of protein complexes created by mTOR. By focusing on mTORC2, the more mysterious of the two protein complexes, Jacinto has unlocked new understanding about its function, its relation to nutrients and identified another possible target for attacking a variety of cancers.

"It is still early and there is still a lot of work to be done," said Jianjie Ma, who has worked over Jacinto for the past two years as her department chair, "but her work has great potential."

In the field of drug development, some of the newest medicines are being created to inhibit the spread of disease by targeting specific proteins involved in cell growth and survival.

There are high hopes that Jacinto?s research will identify more new targets for treating cancer and other diseases. Earlier this year, she won some recognition ? and money ? to bolster those efforts. Stand up to Cancer, a group that combines the celebrity of Hollywood and the clout of top-notch scientists to raise money and fund innovative research, chose Jacinto from more than 100 other researchers to receive a $750,000 grant to help pay for her work.

Beyond the giant pharmaceutical companies that make billions selling new medicines, there are academic research laboratories around the world where scientists like Jacinto carry out meticulous experiments, de-assembling proteins and cells in an effort to better understand why the biological process sometimes goes awry, triggering bad cells ? and disease.

The research done in these tight, brightly lit spaces scattered with laptops and glass instruments may lead to new insights about the biology of a disease or they may produce break-through medicines. When the research shows enough promise, it might be purchased by a large company or spun off to form the heart of a small, new drug-making firm. The goal is to move it into the clinical setting where it can be studied further and developed into a new treatment.

Terri Kinzy, a senior associate dean for research at Robert Wood Johnson Medical School, helped to recruit Jacinto for a professorship in the school?s department of physiology and biophysics nearly 12 years ago. "I think she really is that person who wants to take her research and translate it into the clinic," Kinzy says. "She really wants to increase the impact of her work.

"It?s a big challenge," Kinzy says, "and she likes challenges."

Jacinto?s passion for her work is well-known among her colleagues. She is described as a collaborator and a mentor, who attracts some of the brightest, hardest-working graduate students to her laboratory.

Ma, who has chaired the department for the past two years, says he has, sometimes, come into the laboratory on weekends to find Jacinto writing a paper or working with a student. "For someone already established," he says, "she doesn?t have to work that hard."

Even so, most researchers attribute their successes to a combination of persistence and luck. Ma says Jacinto is someone who has proven she has both.

In some ways, it was an element of serendipity that put Jacinto on the path to becoming a cancer researcher.

"A lot of scientists, when you ask them, say it was their childhood dream to be a scientist. That wasn?t me," Jacinto says. "I didn?t really know what I wanted to do when I grew up, but I liked science and I said, this is close enough to medicine, I?ll do research."

Jacinto flirted with the idea of med school when her family immigrated to San Francisco from the Philippines in 1986. Fresh out of the University of the Philippines with a degree in zoology, she applied to both medical schools and graduate schools. She settled on a Ph.D. program in biomedical sciences at the University of California in San Diego.

In a laboratory managed by Michael Karin, a professor and a world authority on signal transduction pathways that regulate gene expression, Jacinto found herself in the midst of some of the most heady research of the time.

The excitement surrounding protein kinesis ? ground-breaking work at the time ? quickly overtook Jacinto?s interest in reproduction hormones. Today, she says the course of her career was strongly influenced by Karin?s laboratory.

Jacinto says the experience was both thrilling and stressful. There was such intense interest in the science at the time, she says, and such fierce competition among the students for Karin?s time and attention.

At the University of Switzerland in Basel, Jacinto found herself in a more comfortable environment, studying yeast genetics and working alongside Michael Hall, whose research led to the identification of TOR, which continues to influence the development of immunosuppressant medicines.

Jacinto?s own research in Hall?s laboratory led to the discovery that mTOR ? again, the "m" refers to mammalian ? creates two protein complexes, mTORC1 and mTORC2. While the two are considered a pair, they work differently: mTORC2 is not inhibited by the drug rapamycin.

"No one knew the function of mTORC2," Jacinto said. "If mTOR is doing something important, then mTORC2 could have a critical role in cell growth and we could target that as well," she said. "The job was to figure out what it does."

In 2004, Jacinto left Switzerland to accept the position at the University of Medicine and Dentistry-Robert Wood Johnson Medical School. In her Piscataway laboratory, she has been able to advance her understanding of mTORC2?s function in the proliferation of cells.

Kinzy, who helped to recruit Jacinto during the school?s international search, remembers being impressed by the young scientist?s work. "She had this unique view of some unanticipated roles of the mTOR pathway," Kinzy says.

Basic research is considered methodical, time-consuming and expensive and the scientists who do it usually divide their time between teaching and managing research in the lab. Jacinto oversees a research group of five.

"She is a person you bring into an institution," Kinzy says, "and she becomes a catalyst because she brings great energy and ideas."

While Kinzy describes Jacinto as an adept collaborator, she is also an advocate of her own ideas and someone who actively solicits feedback. "You?ve got the graceful art of self promotion when you can talk about your work and get others excited about it," she says.

It may be a particularly good asset for a scientist to have when she is also responsible for raising money to help advance her research. Earlier this year Jacinto applied for a portion of the $9 million in grant money that Stand up to Cancer makes available to young scientists doing cutting-edge cancer research.

Stand up to Cancer, a charitable program of the Entertainment Industry Foundation, focuses its efforts on helping to advance research from the lab to the clinic, where it can be tested to determine if it works as a therapy. The program awards its grants after a grueling, months-long review process.

Jacinto, who ultimately won $750,000 in grant money, began as one of 188 applicants whose letters were reviewed by a 38-member committee, which includes prominent scientists and physicians. The committee chose 43 semi-finalists who were asked to submit full research proposals and then invited 18 to come in for interviews. Thirteen grants were awarded.

Richard Kolodner, one of the scientists who participated in the review of Jacinto?s grant application, acknowledges the intensity of the process. "(The interview) could have been the most serious interview she?s had in her life," he says. "She had to come into a room and submit to questions from some very serious scientists."

"She floated to the top of a very tough competition," he says.

Targeted therapy is one of the latest strategies in the fight against cancer, but there are no guarantees that regulating one protein will make enough of a difference, just as there isn?t a guarantee that a treatment will work effectively for everyone.

Jacinto?s devastation over her daughter?s illness may be more profound because of what she knows about cancer and how it proliferates.

Her daughter?s doctors have assured her that their young patients often fare well with the standard treatment ? a combination of chemotherapy drugs. Yet Jacinto is like any other parent of an ill child who is left clinging to hope that the doctors are correct.

"Hopefully, she responds," Jacinto says. "Knowing what I know about cancer and how things can go wrong and so badly, I just hope they found it early enough."

The hope underlying Jacinto?s work was always that she did not find something that would help cure a disease, then she might discover a piece of the puzzle that could help create a clearer picture of what triggered it. "As scientists we?re interested in understanding things. Finding a cure is considered a plus," Jacinto said.

"All of a sudden, since my daughter?s diagnosis, it?s made me think more about how it?s all very urgent," she says. "A lot of cancer patients are out there relying on us to make discoveries."

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Source: http://blog.nj.com/iamnj/2011/12/estela_jacinto_a_scientist_in.html

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