October 10, 2003

Conn leads program to speed drug discovery

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Conn leads program to speed drug discovery

P. Jeffrey Conn, Ph.D. has been working to acquire the robotic and nanotechnology-based instrumentation needed for high-throughput screening of small molecules. Anne Rayner

P. Jeffrey Conn, Ph.D. has been working to acquire the robotic and nanotechnology-based instrumentation needed for high-throughput screening of small molecules. Anne Rayner

This final story in the series introduces P. Jeffrey Conn, Ph.D., who was jointly recruited by the VICB and the department of Pharmacology.

Timing can make all the difference when contemplating a new venture, and P. Jeffrey Conn knows in his gut that this is exactly the right time for him to be here at Vanderbilt launching the Program in Translational Neuropharmacology, an interdisciplinary effort aimed at making the translation of laboratory discoveries into drug therapies for brain disorders easier and faster.

“The time is right for us to make a tremendous impact on bridging that gap between basic science and therapeutics,” said Conn, Ph.D., professor of Pharmacology and director of the program. “We are in an ideal position to determine our own fate, in terms of developing small molecule tools for biological discovery.”

Conn came to Vanderbilt last spring from the pharmaceutical company Merck & Co. Inc., where he headed the neuroscience program at the company’s West Point, Penn. site. Prior to that, he led a productive pharmacology research laboratory at Emory University. From the vantage of having practiced science in both academia and industry, Conn views Vanderbilt’s potential for success in this area with a sage eye.

“There are things we can do now in an academic setting that 10 years ago would have been impossible,” he said. “As drug discovery has become more automated and technology driven, it’s really a matter of being able to afford the technology and having a culture of collaboration. This is not out of range for a university like Vanderbilt that has a tradition of investing in big science.”

Vanderbilt’s history of investing in strong technological cores sets it apart, says Conn. “That technology has driven the institution and has kept it in the forefront of National Institutes of Health (NIH)-funded science,” he said. “This new program is future oriented and very exciting. I think that just keeps us in this position of strength.”

Another aspect Conn considers key to the program is Vanderbilt’s unusually interactive faculty.

“There are other universities that have the infrastructure, but they don’t have the same collaborative culture and spirit among scientists,” he said.

Such collaboration is exemplified by the Vanderbilt Institute of Chemical Biology, which jointly recruited Conn with the department of Pharmacology. The VICB brings together chemists and biologists from the schools of Arts & Science and Medicine to address biological questions using chemical tools and strategies.

“This activity is going to be aided by VICB and by Pharmacology, but it’s going to be more of an institution-wide activity that will expand also toward clinical research and clinicians,” said Heidi E. Hamm, Ph.D., Earl W. Sutherland, Jr. Professor and Chair of Pharmacology. “What Jeff has accomplished just since April is amazing, and it’s only going to keep accelerating.”

Since his arrival, Conn has worked with Hamm and with Larry J. Marnett, Ph.D., director of the VICB, to acquire the robotic and nanotechnology-based instrumentation needed for high-throughput screening of small molecules. In addition, they have taken steps to purchase large libraries of small molecule reagents.

Scientists use such reagents — substances useful in analysis and synthesis because of the reactions they cause — to help them understand how biological systems work and how to correct that biology when it goes awry, as in disease.

“Much of science is driven by reagents, and it is the scientists who have the tools to ask questions who are really at the forefront and are able to be successful in getting funding,” Conn said. “Having this capability at Vanderbilt will allow its investigators to think outside the box.”

Academic scientists typically design their projects keeping in mind only those reagents that they can buy or get from their colleagues, so they tend to be largely dependent upon drug companies to develop small molecule reagents. Changing the culture so that scientists think proactively about the biology and not about what tools are available is critical, says Conn.

“I think that kind of change is going to really spread at Vanderbilt when people start seeing successes,” he said. “As they see their colleagues solve their questions by developing their own small molecule reagents, they will see how it can benefit them and the idea will just naturally feed itself.”

“That would be a unique role for academia, to have these small molecules and use them as tools to probe the biology of the system,” said Hamm. “The small molecule tools would not have to be the actual drugs that go into people, but they’d have to be good enough to probe the biology and say, ‘Is this a target that, if we could hit it, would actually work on a disease that we’re interested in curing?’

“That is, I think, one of Jeff’s best insights, that you have to be intimately involved with biology,” she said. “And that’s what each scientist is really best at — it’s their whole life’s work.”

The program fits right in, Conn said, with the current climate at the NIH. In a series of far-reaching initiatives known as the NIH Roadmap for Medical Research, Director Dr. Elias A. Zerhouini is unveiling a new strategy designed, he said in a press release last week, “to spark the changes that must be made to transform scientific knowledge into tangible benefits for people.”

“There really is a general shift that I see in the way science is done,” said Conn. “The timing is right to start capitalizing on a lot of the advances we have made in molecular and cell biology and to make that transition to clinical practice.”

Conn has had his hands in translational research for years, beginning back in his days as a graduate student at Vanderbilt. Eli Lilly and Co. funded the research he did under the mentorship of Elaine Sanders-Bush, Ph.D., professor of Pharmacology. Conn went to Yale University for a post-doctoral fellowship, also in pharmacology. While at Yale, he ran a small laboratory at Miles Pharmaceutical. “That was my first serious effort within the pharmaceutical industry,” he said.

After Yale, Conn went to Emory University, where he established an independent lab and eventually achieved full professorship. During his tenure at Emory, he was involved in regular consulting relationships with multiple companies. It was at Emory, he said, that his research “gravitated toward neuropharmacology that had relevance to therapeutics — very much basic, cellular neurobiology, but always with that bias.”

Conn went to Merck from Emory, to head their neuroscience department, but he was also the head of the global effort of the company in schizophrenia and Parkinson’s disease. “Those two interests I took with me to Merck and they’ve continued here,” he said.

“Jeff’s a great scientist, but what he’s also bringing to the table is a knowledge about what academia has to bring to the drug discovery process and how to partner with industry,” said Hamm. “He’ll be very good at forging alliances and collaborations, because he knows both sides of the table. He’s going to be great for this place, he really is. I’m having fun watching what he can do.”