Translational Research in Action
In the spring of 2011, Penn celebrated the opening of the Smilow Center for Translational Research – a new home for Penn Medicine's emphasis on translating breakthroughs in the lab to clinical therapies for patients. The story profiled here is just one example of such research at Penn.
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According to the National Institute for Mental Health (NIMH), up to one quarter of adults are diagnosed for a disorder annually in the United States. Although mental disorders are widespread in the population, the main burden of illness is concentrated among a smaller proportion (about 6 percent, or 1 in 17) who suffer from a seriously debilitating mental illness.
Despite the scope of such disorders, researchers are only beginning to understand the underlying neurobiological causes of these diseases. At the last Society for Neuroscience meeting, in late 2011, many presentations addressed these issues.
Closer to home, work from a team at Penn was featured on the cover of a recent Proceedings of the National Academy Sciences. The article was authored by nine members of the Department of Psychiatry, in the Perelman School of Medicine. Their collective work connects reductions in a brain protein that has been identified as a possible risk factor for schizophrenia – dysbindin – and illustrates how disruption in this protein leads to impairments in how the brain processes sensory stimuli such as sound.
The work highlights how four labs in conjunction with clinical members of Psychiatry at Penn Medicine came together to produce this high impact work. Lead author on the PNAS paper Gregory Carlson, PhD, assistant professor of Neuroscience in Psychiatry, tells the story of how the seemingly disparate lines of research came together.
This research could have ended up as four or five different interesting papers with moderate impact in the field. Instead, we were able to tell a complete story by linking potential genetic risk factors of schizophrenia to a functional disruption in how the brain responds to sound. We then linked those processes together by identifying reduced activity in special nerve cells that are designed to make other cells in the brain work together at a very fast pace.
This unplanned collaboration did not come out of thin air. First, it took the generosity of the main participants to consolidate a number of publishable sets of data together for one paper.
The original finding of reduced dysbindin as a common feature of about 80 percent of schizophrenia cases came from work led by Steve Arnold and Konrad Talbot, which they published in 2004.
To follow this study up they acquired a mouse model of reduced dysbindin to study how loss of dysbindin related to features of schizophrenia, particularly those found in their post-mortem human studies. These mice appeared to be a useful model and eventually were distributed to a number of laboratories within the Department of Psychiatry, sparking productive independent research into the role of dysbindin in schizophrenia. The final step in pulling this project together resulted when the senior author on the PNAS paper, Steven Siegel, MD, PhD, associate professor of Psychiatry, worked with me to bring together all the players and organize a unified publication from multiple laboratories. According to Dr. Siegel, “I’d seen Greg’s presentations for several years and saw this project as the perfect opportunity for Greg’s work to be recognized as the focal point to explain data that many of us were seeing in our individual programs.”
Just as important is a culture of collegiality here at Penn and pioneering program grants from NIMH, such as those led by Raquel Gur, MD, PhD, the Karl and Linda Rickels Professor of Psychiatry. “The Conte Center funding mechanism emphasizes translational research efforts among investigators across laboratories. We are fortunate at Penn to have the breadth and depth and a collaborative spirit across schools that allowed the establishment of a Conte Center, bridging molecular and clinical neurosciences,” comments Gur.
Thus, we were prepared to collaborate, we were willing, and felt institutionally supported within Psychiatry. While our collective number of publications recorded may be less, our collective impact on the field of schizophrenia research and reflected on Penn is much greater.
We are in a resource-limited time. It is harder to support a big lab that can do it all and funders want even more assurances that the science we do makes this sort of impact. Collaboration is something we can do well at Penn.
The generosity and quality of the science shown by authors on the current PNAS paper demonstrate that to our funders and our own community at Penn.
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Carlson GC, Talbot K, Halene TB, Gandal MJ, Kazi HA, Schlosser L, Phung QH, Gur RE, Arnold SE, & Siegel SJ (2011). Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 108 (43) PMID: 21969553