Dr. William E. Cullinan Photo courtesy of Marquette University

“Molecules to man.” That’s how Dr. William E. Cullinan, dean of Marquette University’s College of Health Sciences, describes the scope of the flourishing neuroscience research cluster developing on the Milwaukee campus.

Faculty and students in the college, as well as from other corners of the university, are exploring one of the most exciting frontiers of human understanding, seeking to find solutions to some of the most complex mysteries of our time.

Scientific research programs are aimed at understanding the brain’s stress and reward circuitries, having important implications for mood and cognitive disorders (depression, schizophrenia, post-traumatic stress disorder) and addiction (drugs, alcohol, gambling, feeding).

Additional research focuses have implications for stroke, multiple sclerosis, Parkinson’s disease and Alzheimer’s disease.

This intensive focus on neuroscience has borne fruit: two pharmaceutical companies, a nationally recognized neuroanatomical dissection course and a multidisciplinary neurological research institute.

Neurological research births two drug companies

Four researchers, two labs, one purpose: Develop pharmaceutical agents to help battle schizophrenia, a debilitating mental health disorder that affects 2.4 million individuals nationwide.

Rooted in a novel research project to study the role of glutamate in addiction (most other neuroscientists seemed all but certain that dopamine was the culprit), Dr. David Baker, associate professor of biomedical sciences, and faculty colleague Dr. John Mantsch, launched Promentis Pharmaceuticals, Inc., a startup that could deliver promising new treatments for schizophrenia and other neurological disorders.

It was in his early research that Baker identified a unique mechanism in the brain that releases glutamate, a key neurotransmitter, in an unusual way. His team was the first to show that glutamate released by that mechanism is critical for brain function—and plays a part in brain dysfunction. Although Baker’s focus at the time was on addiction, he hypothesized that this brain mechanism could also be involved in other neurological diseases. In 2004 he decided to turn his attention to schizophrenia.

Though it occurs in only 1 percent of the population, the disease is so disruptive that most schizophrenics can’t function in society, and 10 percent commit suicide. But the medications for the disease are so debilitating and ineffective that compliance rates are abysmal. By finding a better treatment for schizophrenia, Baker hoped to have a real impact.

Armed with research and small business grants from the NIH, a successful experience in a business plan competition, and collaborations with industry veterans and a local chemist, Baker and Mantsch were able to launch Promentis, Marquette’s first pharmaceutical spin-off.

Baker hopes to guide other Marquette faculty through the entrepreneurship process. “I could really make a convincing argument that my story couldn’t have happened at other universities,” he says.

“I really think this is going to change the way the university looks at intellectual property and tech transfer,” Mantsch adds. “This is really something that could define Marquette as a research-intensive institution.”

Down the hall, Dr. Behnam Ghasemzadeh, another faculty member in the biomedical sciences department, and Dr. Daniel Sem, associate professor of chemistry, are embarking on a different journey with the same hopeful goal. Out of their partnership came AviMed Pharmaceuticals.

With more than 18 years’ experience investigating brain mechanisms in psychiatric and neurological disorders, Ghasemzadeh serves as AviMed’s president and chief scientific officer. Sem, an industry veteran, has more than 14 years’ experience in pharmaceutical development. Prior to coming to Marquette, he was vice president for Biophysics and was co-founder of another pharmaceutical upstart, Triad.

Although the Promentis and AviMed teams are working toward the same goal, their approaches are quite different. Promentis is pioneering novel treatments for schizophrenia and other central nervous system conditions, while AviMed is developing molecules and proprietary technology to repurpose existing drugs.

“The schizophrenia drug pipeline is drying up,” Ghasemzadeh says. “Current medications treat only some symptoms and have significant side effects. As a result, 70 percent of patients stop taking medications after 18 months.”

Preserving a lost art

For three July days in a Marquette teaching lab, physicians, psychologists, physical therapists and a host of other medical professionals from all over the country and abroad gather to unravel—quite literally—the body’s most enigmatic organ using blunt dissection, an increasingly rare but valuable method.

“Neuroanatomical Dissection: Human Brain and the Spinal Cord” is an intensive three-day seminar taught by Cullinan.

“Blunt dissection, which was replaced at many institutions in the 1990s by the simpler method of brain slicing, emphasizes the brain’s deeper structures and connections,” says Cullinan, who perfected the technique at the University of Virginia under the tutelage of renowned Swedish neuroanatomist Dr. Lennart Heimer. “Even students in some of the nation’s top medical schools don’t have the chance to meticulously dissect the brain in this way. It’s truly a lost art.”

In one of his last papers, Heimer wrote, “No book, plastic model, or high-tech computer simulation can replace gross dissections as a vehicle for the study of the human brain…No method can provide a better and more easily obtainable overview of the anatomical organization of the human brain than that of blunt dissection.”

Cullinan believes that as the field of neuroanatomy has become more cellular and molecular, there has been a tendency to get away from some of the essentials. The technique employed, he says, is an important first step because it helps one to understand brain components globally and in 3D.

The 2010 course is scheduled for July 15-17.

A collaborative, interdisciplinary approach

While the brunt of neuroscience research is concentrated in the labs of 11 federally funded scientists from the College of Health Sciences’ Department of Biomedical Sciences, researchers across campus are working to unravel the mysteries of the human brain. More than 30 Marquette faculty members from such disciplines as biomedical sciences, psychology, physical therapy, exercise science, biomedical engineering, biological sciences, education and others gather bi-monthly around a seminar series dedicated to neuroscience research.

Under Cullinan’s direction, the Integrative Neuroscience Research Center (INRC) promotes the exchange of ideas among these researchers, thereby increasing opportunities for collaboration, resource acquisition, faculty and student recruitment, and enhanced educational offerings.

The INRC also serves Marquette students by providing research opportunities within the laboratories of its members.

Each semester, the INRC’s seminar series includes guest speakers—leaders in their field—from respected institutions such as the National Institutes of Health, University of Michigan, Northwestern University, Washington University School of Medicine, New York University, University of Chicago, and many more.

No slowing down

The College of Health Sciences is the hub of neurological research at Marquette, but it’s also the youngest of the university’s traditional colleges, established only in 1996. That year, the Department of Biomedical Sciences—where the majority of neurological research is now conducted—opened with three students; today there are more than 550, making it the largest undergraduate academic major at Marquette.

It is one of only a handful of such programs in the U.S. and prepares students for a wide range of healthcare careers including medicine, dentistry, pharmacy and many others. The department’s faculty will be expanded to include seven additional neuroscience professors over the next five to six years.