When Berislav Zlokovic, MD, PhD, returned to USC in 2011 after several years at the University of Rochester, a top goal of his was to boost physiology research funding from the National Institutes of Health, or NIH.

Zlokovic, who had come back to chair the Department of Physiology and Biology at the Keck School of Medicine of USC and also serve as director of the Zilkha Neurogenetic Institute, said at the time, “My role will be to enhance an already very strong neuroscience base and try to make USC the No. 1 place in the neurosciences in the country and the world.”

Seven years later, the department has climbed to third in national rankings compiled by the Blue Ridge Institute for Medical Research. Faculty members in the physiology department have more than quadrupled their grant dollars, with about $16 million in NIH research funding in 2017. The department’s total grant awards from all sources go even further.

The fight for funding is competitive, as researchers nationwide seek to understand neurodegenerative diseases like Alzheimer’s and Huntington’s that afflict so many as the population ages.

But Harvard University neurology Professor Rudolph Tanzi, PhD, director of the Genetics and Aging Research Institute at Massachusetts General Hospital, said that “even in a highly competitive landscape for funding, outstanding research rises to the top and finds the financial support deserved. Under the leadership of Dr. Zlokovic, the Zilkha Institute has consistently carried out the most innovative and highest-impact research in neurogenetics and neurological disease today, earning them a spot in the highest echelons of funding support and truly breakthrough science.”

Researchers are thinking differently

To raise funding levels, Zlokovic encouraged researchers to think differently. Besides applying for grants that advanced their main research focus, he urged them to seek funding for studies using state-of-the art technologies, entering unchartered territories and fields as part of the work.

“There are so many talented researchers here at the Zilkha Neurogenetic Institute. So we have several investigators with two or three NIH R01 investigator-initiated grants,” he said, referring to the NIH’s independent project grants that usually cover four to five years of support for research. Zlokovic’s own grants totaled nearly $5 million for 2017.

Research helps the department find its footing

At the same time, the Keck School’s physiology research efforts have helped the department gel, and the growth of USC’s Zilkha Neurogenetic Institute plays a key part in that.

Faculty members who worked at the institute once belonged to departments scattered across the Keck School, he said, but their funding and complete financial support was funneled through the Zilkha Neurogenetic Institute instead of their individual departments. Since so much of their collaborative work was done with one another, it made sense to reorganize the researchers into a single department within the Keck School.

Working with the chairs of the other departments, Zlokovic consolidated these eight faculty members, who voted to merge into the physiology department. What previously was called the Department of Physiology and Biophysics was renamed the Department of Physiology and Neuroscience in 2017 to better reflect its new focus.

“The Zilkha Neurogenetic Institute is home to a particularly talented group of scientists, all of whom contribute to the overall success of the department,” Zlokovic said. “Without the collective actions of our strong research group, we would not have risen in the ranks as fast as we did.”

Key research funding

Among the dozens of key grants secured by his researchers, Zlokovic cited a few that exemplify the collaborative nature of the faculty’s work.

Protein specialist Ralf Langen, PhD, professor of physiology and neuroscience who directs the Protein Structure Center, received $1.5 million over two years to develop better diagnostics for Huntington’s disease by working with Ansgar Siemer, PhD, assistant professor of physiology and neuroscience, and Tobias Ulmer, PhD, associate professor of physiology and neuroscience, to detect the toxic forms of molecules that cause the disease.

Neuroscientist Terrence Town, PhD, professor of physiology and neuroscience, renewed a five-year, $2.8 million grant, receiving additional funding to create satellite programs led by Russell Jacobs, PhD, professor of research physiology and neuroscience; Paul Thompson, PhD, professor of ophthalmology, neurology, psychiatry and the behavioral sciences, radiology and engineering and associate director of theUSC Mark and Mary Stevens Neuroimaging and Informatics Institute; and Peter Conti, MD, PhD, professor of radiology, all of whom make use of a rat model developed by Town to replicate pathological hallmarks of Alzheimer’s disease in humans. By creating cutting-edge tools, the researchers are evaluating potential therapies that work at the interface of the brain and the body’s immune system.

Zlokovic himself received a $12.5 million multi-year grant from the National Institute on Aging, plus a complementary $3 million strategic grant from the Alzheimer’s Association, to study the role of brain vasculature in cognitive decline associated with Alzheimer’s. The project involves Arthur Toga, PhD, of the USC Mark and Mary Stevens Neuroimaging and Informatics Institute, who co-leads the program with Zlokovic; Helena Chui, MD, chair of the Department of Neurology; and 25 co-investigators across USC, the Huntington Medical Research Institute, Washington University in St. Louis, Banner Institute and Mayo Clinic Scottsdale Arizona.

Zlokovic is also the North American coordinator for the Fondation Leducq Transatlantic Network of Excellence, funded by a $6 million, multi-year grant that unites researchers around the world to study small vessel disease, the primary cause of stroke and dementia in the elderly.

But the department’s strength comes from a wide range of researchers, many of whom have obtained multiple R01 grants from the NIH.

Wide-ranging research

Janos Peti-Peterdi, MD, PhD, professor of physiology and neuroscience, has two such grants and several awards from private foundations and industry for his work exploring kidney functions and the kidney-brain axis in health, and diseases such as hypertension and diabetes that he studies at the cellular level using imaging analysis.

Jeannie Chen, PhD, professor of physiology and neuroscience who studies the workings of the eye, also has two R01 grants, plus multiple subcontracts. Li Zhang, PhD, professor of physiology and neuroscience, collaborates on multiple projects across USC, working with investigators from the Broad Center for Regenerative Medicine and Stem Cell Research, the USC Stevens Neuroimaging and Informatics Institute and the USC Dornsife College of Letters, Arts and Sciences. Zhang also is under consideration for funding of a large five-year grant from the NIH’s BRAIN Initiative, which seeks to accelerate the development and application of new technologies to understand the human brain. Huizhong Tao, PhD, associate professor of physiology and neuroscience who already has two R01 grants exploring visual circuits, is also part of a large BRAIN Initiative grant.

“It was a big goal then,” Zlokovic said, referring to his 2011 return to USC. “But I would say with the support of the faculty, the Keck School of Medicine and the USC community at large, the dean, provost and president, and a remarkable dedication and sponsorship by Selim Zilkha and Mary Hayley, we are now realizing this dream in the Zilkha Neurogenetic Institute all together.”

— Paul Boutin