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Continuous Research Funding
Is a More-Than-Modest Feat BY LESLIE MERTZ When the research team learns that their boss, Samuel Brooks, PhD, is being featured in an article for Wayne Medicine, one member whispers, "You couldn't have picked a better person to do a story about." Another nods and adds, "He is an excellent researcher. He is a very modest man."
Dr. Brooks is professor of biochemistry and molecular biology, and head of the graduate program in cancer biology at Wayne State University, as well as director of education and a member of the senior leadership at the Karmanos Cancer Institute. He is also a WSU faculty member with one of the longest unbroken strings of continuous funding - 35 years through 2002, in fact. And there's the rub - for Dr. Brooks anyway. As the professor sat in his office on the second floor of the Helen Vera Prentis Lande Building, he expressed surprise and more than a little embarrassment that anyone was interested in the continuous funding. After all, he said, other faculty members have received funding over a period of years. "Please don't suggest that I'm the only one," he implored. The fact of the matter is that he has received funding year in and year out for the past three-and-a-half decades, one of the longest funding runs at the university. Dr. Brooks' first grant came in 1964, six years after he received his doctoral degree, when he was working at the Detroit Institute of Cancer Research, the predecessor to the Michigan Cancer Foundation. "Before that I was working with Dr. Jerome Horwitz, the scientist who created (the AIDS drug) AZT, on a grant of his." He and Dr. Horwitz are still collaborators and close friends. After the first grant, the others came steadily but not always as expected. He credits his success more to his willingness to be flexible, to "serendipity" and to the expertise of the people in his lab than to his own prowess.
"When I was in mid-career, I would never have just one grant proposal," he explained. "You can't have all your eggs in one basket. I'd have two at least, so if one didn't make it, the other one did. Often was the time that I would have two grant proposals, and I'd think one was really great and the other was just research that I had to do anyway, but I wouldn't get the first, I'd get the second. That's life. You have to be flexible." He has also found that life in the lab is anything but predictable. "Serendipity is a big part of research. You never know where you're going to go." He explained, "You may set out to find out if 'A' is true, but on the way you find out that 'B' is really what's interesting, and you change and move to examine 'B.' That's serendipity, but that's the fun of it." Another primary ingredient in his funding success, he said, is the men and women who have joined his lab over the years. "People come here who have talents and expertise that I don't have, and they start to show things that I would never have shown." The common thread throughout Dr. Brooks' research is estrogen. He has particularly been interested in the hormone's relationship to breast cancer. "When I started this work, everybody thought that the liver metabolized estrogen into something that was doing the activity. No one even knew about estrogen receptors - they hadn't been discovered. We started to study how a target tissue treats the estrogen molecule, but I could see that this wasn't going to be fruitful and probably wouldn't continue to be funded, so we opted years ago to follow the newly discovered estrogen receptor." The path of his research has many twists, he said, and most recently the trail has followed the expertise of two researchers in his lab. "We got into proteins, which I didn't have a lot of insight into, but people came to work for me who did - like Jan Schwartz. She's very interested in protein-protein interactions, and a lot of our work is going in that direction now." His current four-year grant to study these interactions lists him as the principal investigator and Schwartz as co-principal investigator, but he hastened to add, "We really got the grant because of Jan's work." Since they applied for the grant, Dr. Schwartz has moved up from post-doctoral fellow to assistant professor of physiology at the university, Dr. Brooks noted. "The work in protein-protein interactions slightly changed our lab's direction, but that was the direction that was most interesting," he said, again pointing to the importance of flexibility and the unpredictable nature of research. With the grant, Drs. Brooks and Schwartz will be looking into the roles of co-activator and co-repressor proteins in the regulation of estrogen responsive genes. The information they learn about these mechanisms will provide insight into potential methods to control estrogen activity in hormone-dependent breast cancer, as well as osteoporosis, endometrial cancer and fertility. Not surprisingly, Dr. Brooks is already writing another grant proposal, this time with Guozhen Liu, who earned his PhD from Brooks' lab in October, 1999. "This one is a lot of fun," the professor remarked. "Guozhen came in here with a whole different point of view. He started to show things that we never suspected about how estrogen receptors work with the tumor suppressor gene P53 and the oncogene hdm2." Basically, he said, hdm2 interacts with P53 to limit its lifespan and activity, and the estrogen receptor prevents the interaction. "The receptor protects the cell from the oncogenic (cancer-causing) pressure of hdm2. Nobody had shown this." One of the most interesting aspects of the finding is that the estrogen receptor doesn't even require estrogen to function in this manner. Dr. Brooks says he appreciates the new perspectives of Dr. Liu and others who have enhanced the collective work in the lab. Dr. Brooks said the new avenues of investigation are exciting. "Because of this you don't get bored, but you have to be willing to change your concepts and re-target your objective as things are learned." Of the continuous funding, all of which has come from various units of the National Institutes of Health, he gave this summary: "I didn't do all of this myself. I'm just a facilitator." True to form, he requested that any photograph used to accompany this story include all five members of his research group.
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