Environmental Factor, August 2007, National Institute of Environmental Health Sciences

Cell Biologist Delivers Final Lecture in Scientific Director Series

By Eddy Ball
September 2007

Although he would set up a lab at NIEHS to pursue his research interests, Juliano speculated that he would have to give up one of his two lines of research if he is selected as Scientific Director. (Photo courtesy of Steve McCaw)

Wilson hosted the lectures and moderated question-and-answer sessions for each of the top three candidates chosen by the search committee. His questions to Juliano helped to ensure that each candidate had the opportunity to respond to a set of core questions about vision and leadership. (Photo courtesy of Steve McCaw)

Joyce Goldstein, Ph.D., pondered Juliano’s answers. Wilson asked the candidate about conflict resolution, a topic Goldstein herself had addressed at a previous lecture in the series. (Photo courtesy of Steve McCaw)

Colleagues Mike Resnick, Ph.D., left, and Ken Korach, Ph.D., shared their impressions of the candidate. Both are group leaders who could be affected by how skillfully the next Scientific Director serves as a broker among stakeholders. (Photo courtesy of Steve McCaw)

A lecture by Rudy Juliano, Ph.D., on August 6 brought the NIEHS Scientific Director Lecture Series to a close. Juliano spoke on "Integrin-Mediated Control of Cell Signaling Events" to a near capacity audience in Rodbell Auditorium. Following the lecture, he fielded questions from the audience about his management philosophy and his vision for the future of the Division of Intramural Research.

The candidate is the Cary C. Boshamer Distinguished Professor and former chair of the Department of Pharmacology at the University of North Carolina (UNC) at Chapel Hill. Juliano also serves as principal investigator at the National Cancer Institute-funded Carolina Center of Cancer Nanotechnology Excellence, where he oversees six research projects related to the use of nanoparticles in cancer therapy and imaging. His lecture was hosted by NIEHS Deputy Director Samuel Wilson, M.D.

Although Juliano has worked in cell biology since his postdoctoral fellowship at Roswell Park Memorial Institute, he reminded the audience that he earned his doctorate in biophysics — helping explain the distinctive mix of his research interests. Juliano described his two-fold research program at UNC as "sort of schizophrenic," embracing as it does his lab’s basic research into cell adhesion molecules and signal transduction and the more translational orientation of his work in the development of macromolecular therapeutics for delivery of drugs.

Juliano’s cell biology research has focused on the biology, biochemistry and molecular biology of the integrin family of membrane receptors. Integrins are a large family of cell surface proteins that regulate key signaling pathways, particularly those involving enzymes in the group of mitogen-activated protein kinases.

Integrin-mediated signals help to control gene expression and can influence cell differentiation, progress through the cell cycle and apoptosis. "There have been a number of knockouts of the various integrin subunits," Juliano explained, "and these have led to insights showing that integrins play a very important role both during development and in maintenance of normal cell interactions."

According to Juliano, integrins perform two important functions. In a structural context, they form a "physical bridge" across cellular membranes. In terms of inter-cellular communication, they modulate a variety of signal transduction processes. Aberrations in these cell interactions are hallmark characteristics of the invasive and metastatic behavior of malignant cells.

From his overview of the roles of integrins, Juliano moved on to a discussion of recent research in his lab involving a novel large integrin-binding protein called Nischarin and a cell-proliferation protein known as deleted in liver cancer 1 (DLC-1), both of which are associated with changes in normal cell interactions and tumor growth. In rodent studies, when Nischarin, which means "slow moving" in Sanskrit, is over-expressed and bound with the alpha five subunit of integrin, the protein strongly "down-modulates" cell motility and disrupts normal cytoskeleton organization by inhibiting the activity of a class of enzymes known as PAK-kinases. In carcinogenesis, low Nischarin levels coincide with more vigorous tumor development.

For its part, DLC-1 has emerged as a candidate tumor-suppressor gene. "What has gotten cancer biologists excited about DLC-1," Juliano observed, "is that when this molecule is over-expressed in a variety of carcinomas, there is a significant inhibition of tumor growth and proliferation of tumor cells." Named for its absence in liver cancer, DLC-1 has also been observed as missing or inactive in many breast cancer lines.

This initial work by Juliano’s lab to increase understanding of the mechanisms of integrins and the proteins Nischarin and DLC-1 has turned up intriguing possibilities. The lab has been able to reverse the effects of Nischarin over-expression and DLC-1 deletion, suggesting that one day these molecules may prove to be useful targets in therapeutic interventions.

Juliano on Vision and Leadership

Like the previous candidates, Juliano spent fifteen minutes before the audience answering questions about the kind of leader he might be and his vision for the future of the Division of Intramural Research (DIR).

Wilson opened the session with a question about how the candidate sees the management and evolution of the DIR over the next five years. "I think one of the key roles of the Scientific Director is to be highly involved in implementing the aspects of the Strategic Plan that relate to the Intramural Research program," Juliano answered. "I think you have a very good guideline for where you want the Institute to go. I guess the question is how to maximize Intramural resources… [and] to make sure that very high quality science is maintained."

David A. Schwartz, M.D., posed questions related to training, the development of minority leadership and the candidate’s reasons for wanting to take on the responsibilities of the position.

In his responses, Juliano pointed to his years of experience with postdocs in his labs and his understanding of the difficulties they face in making the transition from trainee to successful independence as a junior investigator. He also referred to his experiences at UNC recruiting and promoting minority and female scientists. For both groups, he stressed the importance of mentoring and role models.

The candidate provided a thoughtful answer to one of the important questions on everyone’s mind — why he would exchange "the pretty pleasant life" of a senior professor at a major research university for the challenges of administering DIR. "The interesting thing for me," he answered, "would be to have the chance to essentially ‘write on a larger slate’ in terms of developing new initiatives and new programs and also in terms of managing programs that already have a good dynamic."

Juliano also referred to the potential for influencing the future of environmental science. "I think there are lots of opportunities here to bring new perspectives and new technologies to bear on programs in the Institute."

In terms of conflict resolution and management, Juliano emphasized that "someone in a senior administrative position needs to serve as an honest broker." Like a university department chair, the Scientific Director has to deal with "hot button issues" such as space allocation. "You want to come out of [these kinds of interactions]," he elaborated, "with people feeling, if not good, at least that they’ve been treated fairly."

"When you go to a larger scale [as I will if I move from department chair to Scientific Director]," he said, "you have to be able to delegate responsibility.… [But] I think you also need to keep your fingers on the pulse of what’s going on."

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