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COUNCIL: State of the University
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October 28, 2008, Volume 55, No. 10

Executive Vice Dean and Chief Scientific Officer, School of Medicine, Glen Gaulton

The following is a transcript of his presentation.

Speaking from the School of Medicine’s perspective, our challenge as an institution—and I will discuss this in the context of our relationship with the University as a whole—is merging great basic science with clinical applications. We are, after all, a School of Medicine and you can’t make great clinical discoveries and breakthroughs without having great basic science as a foundation—and we never want to lose sight of this. 

One of the big challenges in a large school like the School of Medicine—a School with 28 departments, 18 centers and institutes, 1,700 plus faculty, 2,000 plus trainees—is developing a cohesive vision, getting everybody on the same page.  For example, we want to make sure that we are developing trainees at the same standard of excellence across our full spectrum of programs: this means undergraduates, medical students, graduate students, both doctoral and masters, postdoctoral trainees, and clinical fellows. This continuum of training is critically important because these trainees will become the next generation of leaders in medicine. 

The School of Medicine also has to improve its infrastructure. Science today is bigger, requires more interdisciplinary funding opportunities, and has greater needs for expensive equipment. We have to provide this centrally: we cannot simply rely on individual laboratories to coordinate these efforts and raise these funds.

The good news is that Penn Medicine is uniquely situated to address these challenges.  To illustrate this today, I’m going to focus on a couple of examples within the Neurosciences.

Following the appointment of Dr. Rubenstein in 2001, one of the first things the School did was develop a cohesive strategic plan, and a big component of this plan concerned the Neurosciences. We formed a Comprehensive Neuroscience Center to coalesce efforts through the School, and to bridge to the Health System, so that we could have a unified entity and vision moving forward. 

One of our early advances was to develop an integrated clinical service model. While this might appear less important on the scholarly side, it actually does play a key role in scholarship—and I will point to this when I talk about the neurodegenerative diseases. On the research front, technologic, basic, and disease-based research approaches are critical.  

I will focus on an example in neuroimaging and an example in the neurodegenerative diseases to illustrate how it is critically important that we translate our basic research discoveries into new therapies and cures. 

Here is an example of an imaging application [referring to a slide].  I don’t know whether these individuals have been watching the presidential debates—perhaps not this individual with that smile! Raquel and Rubin Gur in our Psychiatry department conducted this work.  They showed a variety of pictures to individuals and then measured their brain activity using a non-invasive technique called functional magnetic resonance imaging.  Essentially, this enables the Gurs to map regions of the brain: so, as you can see here, the yellow regions are areas that have become metabolically active.  These are the neurons getting turned on as individuals see faces that elicit different emotional responses. 

This is a panel of men and that is a panel of women —and you see the men light up a little more aggressively than the women do.  I don’t know whether that’s a good or a bad thing!  And the key brain regions that we stimulate are here, just off center, with the amygdala and the outer part of the cortex shown below.  When you look at a schizophrenic patient, on the other hand, you see almost no response whatsoever.  On a physiologic level, these individuals have withdrawn from these responses. Those who are familiar with schizophrenic patients will recognize this response as characteristic of the outward disease phenotype.

The key here is that we can use imaging to study very complex diseases of the brain which otherwise would be impossible to approach.  How does the School of Medicine move forward in supporting imaging in the Neurosciences? We plan to recruit approximately four new faculty in this area over the next five years, which will require about $6 million in resources.  These positions are in addition to the senior PIKs that we’ve already spoken about. 

A year and a half ago, we established an Autism Center. I should add that functional magnetic resonance imaging is absolutely critical to studying autistic children in particular because we want to use non-invasive techniques to understand their brain functions. We are spending about a million dollars a year on supporting this new center. Last year, we recruited Robert Schultz from Yale University who is in our pediatric department to lead this effort. 

We have developed and purchased 3 new MRI scanners—2 of which are on site now—and a 7 Tesla, a very high-end MRI that will be installed within the next year.  

Importantly, in partnership with the School of Arts and Sciences, we have a commitment to coalescing The Center for Cognitive Neuroscience, led by Martha Farah, with the Center for Functional Neuroimaging, which lies in our department of Radiology, led by John Detre. This will bring together, in space that we are jointly renovating in the Goddard and Richards Buildings, over seven thousand net square feet of space. 

In time this space will grow to two to three times this, to bring together individuals throughout the campus whose research focuses on the cognitive sciences, which of course is a component of Neurosciences. Imaging also serves as an important focal point for the School of Medicine in our global initiatives. Led by Jim Gee in our Radiology department, we are partnering with Shanghai Jiao Tong University to create a joint imaging institute.  There are numerous opportunities here—and imaging is the key as we move forward with research in the Neurosciences.  

My second example will focus on a neurodegenerative disease. The unfortunate statistics are that, as we age, we have a higher and higher incidence of Alzheimer’s disease. For individuals 85 and above, roughly 50 percent will develop Alzheimer’s disease [referring to a slide].  If we look at the population of our country overall, we can predict what will happen to the baby boomers as they age, and how many individuals by 2050 will reach the age of 65 or 85. It is estimated that approximately 14 million Americans will have Alzheimer’s disease by 2050, up from a little over 4 million now, with an annual cost of care in today’s dollars of over $6 billion a year.  This alone will bankrupt our healthcare system.

So we really need to do something in this area. Not so much because of pure economics but because, as you all know, of the tremendous toll that this disease takes on individual lives and on families. This is a classic example of translational science in action.  At the research bench, basic scientists at Penn identified protein misfolding in Alzheimer’s disease. These are the proteins that bundle up and coalesce and then essentially destroy neuronal function.  Virginia Lee and John Trojanowski in the Department of Pathology and Laboratory Medicine lead this work. We also have numerous individuals working on animal models of neurodegenerative disease from mice (Benoit Giasson in Pharmacology) to flies (Nancy Bonini in the Biology department). 

Several faculty are now using these models in testing new drugs to see if we can move these drugs to human application. Virginia Lee and Amos Smith in the Chemistry department are among the leaders in this collaborative effort. This is only one example of many bridges between SAS and the School of Medicine.
At the bedside, tissue and DNA banks from patients are critical to advance our understanding of this disease:  indeed, under the direction of Les Shaw and John Trojanowski, Penn is the national tissue distribution center for the Alzheimer’s disease Neuroimaging Initiative.

Gerard Schellenberg leads the national Alzheimer Genome Wide Association Study that recently was funded by the National Institute on Aging to find genetic risk factors for Alzheimer’s disease. In imaging, we’ve also developed new imaging reagents to track protein misfolding, led by Dan Skovronsky and Dr. Lee. 

Lastly, we have pioneered an integrated patient care model led by Steve Arnold, in our department of Psychiatry, Chris Clark, a neurologist, and Mary Naylor in the Nursing School.  When Alzheimer’s patients come to Penn, they receive comprehensive care.  They do not just see a gerontologist or a neurologist.  They see a neurologist, a psychiatrist, a gerontologist and a nursing specialist, so that they get all aspects of care in an integrated fashion. 

Our commitment in this area is, I think, extraordinary. Over just the last two years, we have recruited the following individuals:  James Shorter, to our Department of Biochemistry and Biophysics, and Aaron Gitler, to our Department of Cell and Developmental Biology.  Both of these individuals recently won NIH New Innovator Awards, one of the most prestigious awards for young investigators. 

We recruited Gerry Schellenberg from the University of Washington last year, a very distinguished investigator, who leads our genetics effort.  And David Wolk will be joining us from the University of Pittsburgh as a neurologist working at the clinical interface.  

Our future commitment is to recruit 5 junior and/or senior level faculty.  For program support, we have invested over the last two years about $7 million through the Comprehensive Neuroscience Center and other seed funds to prime the pump in key areas to support educational programs for trainees.  Our total commitment over the next 5 years will be between $10 and $15 million. 

This is also an area that is ripe for collaboration with industry.  Within the last six months, we have signed a $5 million per year agreement with Pfizer and we have a preexisting $2 million per year agreement with AstraZeneca for drug development in these areas. This totals $21 million over the next three years.  Lastly, we have been very successful in fundraising in this area through the generous support of the Ware Foundation and others. 

I am going to conclude with a review of facilities [referring to a slide]. For the cognitive imaging area, we are renovating the Goddard and Richards buildings. Specifically for neurodegenerative diseases, we are renovating elements of the Maloney and Morgan buildings: about 4,000 square feet. The new Fisher Translational Research Center, which is going up now, will be built in two phases. Phase 1 will be completed in the summer of 2010, which will be the upper three floors and one vivarium floor. It is intimately connected to our new Perelman Center for Advanced Medicine. Translational science and components of our neuroscience community will be located in this new building as well.

 

 

 

Almanac - October 28, 2008, Volume 55, No. 10