Receiving the Family Medicine Research Award (from left) is Stephanie Shaw and...
By Lisa Brown
Submissions due March 27
Exhibit Monday-Tuesday, March 30-31
BUSM Instructional Building, 14th floor Hiebert Lounge
All students, faculty and staff at the Boston University Medical Campus are encouraged to submit artwork of any medium to the 25th annual “Art Days”, founded by former BUSM Dean Aram Chobanian to foster the support and growth of the creative arts at BUMC. The exhibition is mounted by the Creative Arts Society.
This is the fourth year of a university-wide arts initiative with an annual Keyword to be used as a thematic organizer for various courses and events. The Keyword for this year is INTERSECT. There may be a special section at Art Days for display of works addressing Intersect. However, it is also fine to submit work not related to the Keyword.
Submissions are due March 27. Paintings, photos, poetry, sculpture, needlework, etc. will be accepted. Pieces should be framed if possible. Security will be provided. Works will be returned April 1. Specific instructions will be sent at a later date to those who respond to this announcement.
To be placed on the submit list or if you have any questions please contact Keith Tornheim, PhD, 638-8296 or firstname.lastname@example.org.
Alzheimer’s drug may reduce urge to eat compulsively
Binge-eating disorder affects nearly 10 million American adults, by some estimates. It’s a vicious condition in which people repeatedly eat huge amounts of food—often high-calorie sweets and/or fatty snacks—in a couple of hours or less. Perhaps the worst part of the disorder is that each binge leads to feelings of embarrassment, self-disgust, and depression.
Now, new research from School of Medicine scientists, published online in Neuropsychopharmacology, demonstrates that an Alzheimer’s drug called memantine may reduce the impulse to binge eat by acting on an area of brain associated with addictive behavior. The research, funded by the National Institute on Drug Abuse and the National Institute of Mental Health, may eventually lead to new treatments for the disorder.
“The disorder resembles addiction more than any other eating disorder. Binge eaters understand the consequences of their behavior, but they can’t stop. It’s a compulsion,” says senior author Pietro Cottone, a MED associate professor of pharmacology and psychiatry and codirector of the Laboratory of Addictive Disorders.
Cottone, who has been studying addiction for over a decade, says that binge eating triggers patterns of chemical responses in the brain that are similar to those in drug and alcohol addiction. In all these disorders, he says, a region called the nucleus accumbens, which provides a communication link between the emotional and reasoning centers of the brain, is particularly important because of its role in eliciting and modulating behavior.
“When you eat, have sex, do drugs—all that stuff—this area gets activated,” says Cottone. During binge-eating episodes, the nucleus accumbens does not function properly. That’s where the Alzheimer’s drug memantine comes in.
Memantine blocks receptors in the brain that bond with glutamate, a neurotransmitter known to stimulate neurons. In Alzheimer’s disease, dying brain cells release excess glutamate, which overstimulates healthy cells and can kill them. So by blocking glutamate receptors, memantine protects healthy cells in the Alzheimer’s brain. Cottone suspected that the drug, by blocking glutamate receptors, could also curb binge eating. With glutamate locked out, he believed the nucleus accumbens wouldn’t reinforce the stimuli associated with junk food so much, and the urge to binge eat should fade.
Cottone tested the hypothesis with two groups of rats. One group was fed a diet of regular rat food. The others also got regular food, but for one hour a day they were also offered junk food, which contained an extra dose of sugar. It was the rat equivalent of jelly beans and gumdrops, and “they loved it,” says Cottone.
Within days, the junk food rats started bingeing. “We made them into binge eaters just by giving them access for one hour,” he says. “It was insane.” And even worse: the more the rats binged on junk food, the less they ate the regular food. “Exactly what happens in people, we did with rats,” he says.
Cottone wondered if the binge-eating rats would take more risks to reach their junk food. He put the rats into a box that was half dark and half brightly lit. Rats are nocturnal and will usually do anything to avoid bright light: when he put a bowl of junk food in the middle of the bright box, the regular-chow rats wouldn’t touch it. “They don’t even think about eating the food,” he says. “They were like, no way!” But the binge eaters couldn’t stop themselves—they ran into the light, stuck their snouts into the junky kibble, and gobbled it up. “This is a lapse of judgment,” says Cottone, noting that such behavior is a hallmark of addiction. “They know the environment is potentially dangerous, but they go there anyway.”
All this changed when memantine entered the mix. The scientists injected the drug into both groups of rats. In the regular-chow rats, it had no effect. But for the binge eaters, the changes were profound. Not only did their binge eating decrease dramatically, but they were no longer willing to take risks to get their junk food. The scientists found the same effect when they injected memantine directly into the shell of the nucleus accumbens.
Cottone and his team hope that memantine may prove a useful treatment for binge-eating disorder, for which there are currently no Food and Drug Administration–approved drugs. “Individuals with binge-eating disorder have a very poor quality of life. Our study gives a better understanding of the underpinning neurobiological mechanisms of the disorder,” says article coauthor Valentina Sabino, a MED assistant professor of pharmacology and psychiatry and codirector of the Laboratory of Addictive Disorders.
Although one small 2008 study in the International Journal of Eating Disorders found that memantine may be useful for treating binge eating in humans, there has been little additional research in this area. “We hope that this paper will help revitalize this line of research,” says Cottone, who anticipates seeing larger, more robust human trials in the future. “We need more pharmacological approaches.”
A version of this article appears on the BU Research website.
This BU Today story was written by Barbara Moran. She can be reached at email@example.com.
The Grasberger Research Symposium Lecture and Visiting Professorship is an annual research event that provides an opportunity for the surgical residents, faculty and staff to present original basic and clinical research. Now in its 24th year, the event will be held on Friday, March 13. This year’s visiting professor will be K. Craig Kent, MD, A.R. Curreri Professor of Surgery and Chairman, Department of Surgery, University of Wisconsin.
K. Craig Kent, MD
Dr. Kent for the past five years has served as the A.R. Curreri Professor and Chairman of the Department of Surgery at University of Wisconsin. Prior to his arrival to UW, Dr. Kent was Chief of the Division of Vascular Surgery at New York Presbyterian Hospital. In 2001, following the merger of New York and Presbyterian Hospitals, Dr. Kent was asked to assume the role of Chief of the combined Columbia and Cornell Division of Vascular Surgery as well as Director of the Vascular Service Line for New York Presbyterian Hospital.
Dr. Kent received a BS from the University of Nevada and his medical degree from the University of California, San Francisco. He completed a General Surgery Residency at the University of California, San Francisco and a Fellowship at Brigham and Women’s Hospital where he was the John Homan’s Vascular Surgery Fellow. In 1988 Dr. Kent joined the faculty at Harvard as an Instructor in Surgery. After being promoted to Associate Professor, Dr. Kent was recruited in 1997 to New York Hospital/Cornell.
10th Annual John McCahan Medical Campus Education Day
SAVE THE DATE
Wednesday, May 20
8:30 a.m.-3:15 p.m., Hiebert Lounge
*Abstract and workshop submissions open Feb. 23*
Attend Education Day to:
- Network with other creative educators in the BUMC community
- Showcase your innovations and ideas in classroom, clinical and lab teaching
- Cultivate your teaching skills
- BUMC faculty, fellows, residents, students and staff who are interested in educational innovations and scholarship are encouraged to participate.
For more information go to http://www.bumc.bu.edu/jmedday/
Sponsored by the BU Schools of Medicine, Public Health, Goldman School Dental Medicine and Division of Graduate Medical Sciences
BU faculty, fellows, residents, students and staff interested in traumatic brain injury, dementia, and brain aging are invited to this workshop. Join with other BU investigators to explore opportunities to maximize utilization of the Boston University Alzheimer’s Disease and Traumatic Encephalopathy Center resources across the University.
Brief presentations by BU ADC investigators (40 minutes)
Small group discussions (1 hour) may include:
- clinical trials, biomarkers and cognitive neuroscience
- cellular and molecular mechanisms
- genetics and epidemiology
Wrap up and readout from discussions (20 minutes
BUMC Provost Workshop
“Accelerating Research on the Chronic Effects of Traumatic Brain Injury and Brain Aging”
Tuesday March 10
3-5 p.m., Hiebert Lounge
Today’s physicians require an increasingly comprehensive understanding of the principles of genetics and genomics in order to make informed clinical decisions. Scientific discoveries are bringing genomic technology directly to consumers at an increasingly rapid pace. The availability of genomic information necessitates that educators provide adequate training in genetics and genomics for future health-care providers.
In a new study in the journal Genetics in Medicine, researchers have shown that genetics curricula are evolving to include current topics in genomics however the majority of the content is taught in the first two years of medical school, with minimal and declining formal instruction in genetics during years three and four.
This study was the result of a survey of course directors in the U.S. and Canada who teach genetics to medical students. The survey collected information on what topics are currently being taught, how they are taught, who the instructors are, how student learning is evaluated, what strategies are used when students do not pass the subject at their schools.
Medical schools that participated in the survey used a variety of innovative teaching strategies to bring genetics into medical training including using integrated curricular models, as well as diverse and innovative teaching and assessment strategies. “We found the curriculum has evolved to include topics of particular relevance to the practice of genomic medicine, including personalized medicine, direct-to-consumer genetic testing, genome wide association studies, pharmacogenetics and bioinformatics,” explained corresponding author Shoumita Dasgupta, PhD, associate professor of medicine at Boston University School of Medicine (BUSM). “However, while important topics emerging in genomic medicine are frequently being added to the curricula, more than 40 percent of the responding medical schools in the U.S. and Canada still don’t teach them,” said Dasgupta.
According to Dasgupta and her colleagues, in order to produce genomically literate physicians, it is critical to improve the coverage of topics relating to genomic medicine. One way they recommend is to increase exposure to these topics by promoting more integration of genetics across the four-year curriculum and highlight existing genetics topics in core clerkships. “These results point to an opportunity to extend formal training in genetics across the entire medical school continuum,” she added.
The researchers suggest concrete steps are needed to ensure the readiness of future physicians to practice genomic medicine, including increasing clinical exposure to genetic topics both locally and through curricula developed by national organizations such as the Association of Professors of Human and Medical Genetics, tracking student performance in the subject even when taught alongside other topics, and involving genetics experts in curriculum development and student mentoring.
“This is a pivotal moment in clinical genetics, and as educators, it is our responsibility to ensure our graduates are prepared to practice in the era of genomic medicine. While powerful technologies that allow whole genome analysis gain traction, it becomes increasingly critical to train the next generation of future physicians to translate genomic technologies and discoveries into their clinical practice across a range of specialties and practices,” said Dasgupta.
Funding for this multi-institution study was provided by the Association of Professors and Medical Genetics.
MED neurologist on battered brains, tangled tau, and the future of sports
For Ann McKee, every brain tells a story. And sometimes it’s a tragic one. McKee, a School of Medicine professor of neurology and pathology, is the director of neuropathology for the Veterans Affairs New England Health Care System and also directs BU’s Chronic Traumatic Encephalopathy Center. Chronic traumatic encephalopathy (CTE) is a degenerative brain disease found in athletes with a history of repetitive brain trauma. McKee first identified its telltale mark—tiny tangles of a protein called tau, clustered around blood vessels—in the dissected brain of a boxer who had been diagnosed with Alzheimer’s disease.
Although most people associate CTE with professional football players, McKee has found it in the brains of soccer, hockey, rugby, and baseball players as well. Her research has alerted the public to the long-term dangers of repetitive hits in sports and raised tough questions about safety. McKee was invited to speak about this growing public health concern at the annual meeting of the American Association for the Advancement of Science, the world’s largest general scientific society, held February 2015 in San Jose, Calif. She told BU Today the story behind her discovery of CTE, and what it might mean for the future of sports.
BU Today: You’re a world expert on tau protein, which has been implicated in Alzheimer’s, CTE, and other brain diseases. Have you studied tau your whole career?
McKee: Yes. I love tau.
It’s beautiful, the way it collects throughout the nervous system and just sort of fills up the nerve cell. It’s always been quite lovely to look at, visually captivating. I mean, how crazy is that? But it’s true.
When you started studying tau, you were studying Alzheimer’s disease?
I was interested in Alzheimer’s, but I also worked on PSP (progressive supernuclear palsy), and something called corticobasal degeneration.
Those are not so famous.
No, they’re not so famous. But I got very involved in defining what these individual diseases looked like. It’s like being at the Smithsonian and being really interested in one collection of pottery or something. And once you start understanding it, you start seeing all these differences, and it’s like, Whoa!
Do you remember the first time you saw a brain with CTE?
Yes. It was phenomenally interesting. The first case was Paul Pender, a professional boxer here in the Boston area. He had twice been world champion. That was my first time seeing it under the microscope. I looked at the slide and it was like, Oh, my God. This is so amazing. I’ve never seen anything like this. It just blew my mind. That was 2003.
How did it look different than, say, a brain with Alzheimer’s?
Alzheimer’s disease has these beta amyloid plaques that look like small puffs of smoke throughout the brain. You have to have these plaques in fairly high numbers to make the diagnosis of Alzheimer’s disease. In most cases, and certainly below the age of 50, CTE doesn’t have any plaques. The other difference is the tau pattern. Tau clusters in little tangles, and in CTE they’re always around blood vessels. So the blood vessels are a clue to the origins of CTE—we think it might be damage to the vessels and leakiness of the vessels that’s causing it.
How did you end up with this boxer’s brain?
He was a veteran and died at the Bedford VA with a diagnosis of Alzheimer’s disease. And there was no amyloid, so it was like, well, it’s not Alzheimer’s disease. And the tau pattern was so unusual that I asked my technician to do this very old technique that people used to use in neuroanatomy before everything was automated. It’s difficult—you cut the brain very slowly in these big sections that contain the whole hemisphere, then you have to stain it while it’s floating in water, and then you have to very painstakingly lay it all out on the slide. It was amazing, because it allowed you to see the landscape of the brain. So it’s phenomenally informative. It allows you to see nuances that you can’t really appreciate with tinier, thinner specimens. The technique contributed to our recognition that this was really something quite extraordinary. This was something really different.
That was 2003. Was CTE a known disease?
Not really. It was primarily called dementia pugilistica and most people thought it affected only boxers. Then, in 2008, I had the opportunity to look at a football player who had had some cognitive issues, and it was like, Oh, my God, another one. And what I couldn’t believe was that the football player was 45. If you’re used to studying neurodegenerative diseases, 45 is incredibly young. So after that case, we started the center and started collecting more brains. The next brain we got was from a football player who died at the age of 45, too. And it was the same disease. It was like, What? Holy Christmas.
And you now have 240 brains in the CTE bank. Are most of them football players?
Yes. We have more football players in the bank than any other sport. But we have boxers, we have hockey players, we have a few soccer players, a couple of rugby players. We have military.
When CTE started coming into the public perception, it was just about the NFL. Now it’s getting bigger and bigger.
That’s exactly right. We’ve seen it in all these professional players, but we’re finding it in nonprofessional players, college players. And I think, from the public health perspective, that’s what’s really important.
Are there implications for kids’ sports?
There’s a lot of interest now in heading in soccer, because that would be something easy to take out. It wouldn’t destroy the game, especially at the lower levels. But also in football, which is such a hugely popular sport, we need to understand the risks for young athletes and reevaluate whether or not young kids should even be playing this game. Their bodies are immature, their necks aren’t very well developed, they’re not very coordinated. Plus, they’re literally walking bobbleheads with big heads, thin necks, and small bodies. Your brain is adult-size by age four, and it’s relatively heavy for those little bodies. The only good thing is, they’re low to the ground.
What surprises you most about CTE?
The thing that is shocking to me, and continues to be shocking, are the 25-year-olds who have died with this disease. Not because of it—it’s usually a suicide or an accidental death. I can’t say that CTE caused their suicide. But for me, it’s shocking to see neurodegenerative disease in a 25-year-old. It’s horrible. And it’s undeniable. We’ve seen it in enough 20-somethings now that you can’t escape this. It’s a shock to think, that guy looks so young, and he’s dead. And he’s dead with this.
A version of this story appears on the BU Research website.
This BU Today story was written by Barbara Moran. She can be reached at firstname.lastname@example.org.
Let’s face it: salt is delicious. Sprinkle it on tomatoes and they pop with flavor; shake it over popcorn and it’s movie time. Even Nelson Mandela noted its worth in his inaugural address: “Let there be work, bread, water, and salt for all,” he said.
But when it comes to diet and high blood pressure, salt has long been one of the bad guys, right up there with (and related to) bacon and bologna. Too much sodium can make your body retain water, increasing pressure within blood vessels and leading to hypertension. And runaway blood pressure can lead to a host of maladies, from kidney damage and vision loss to stroke and heart disease. Hypertension is directly responsible for almost 13 percent of all global deaths, according to the World Health Organization, and the American Heart Association urges us to take an online pledge to trim salt from our diets. The association’s slogan: “I love you salt, but you’re breaking my heart.”
Most Americans do eat too much salt—3.5 grams of salt each day, more than 7 times what we need, according to the Centers for Disease Control and Prevention. But the extra salt doesn’t affect everyone equally. According to Richard Wainford, a School of Medicine assistant professor of pharmacology and medicine, only an estimated half of adults are salt-sensitive: if they eat too much salt, their blood pressure goes up. For the other half, salt has little or no effect on blood pressure. But nobody knows exactly why, and there’s no easy way to tell who’s who.
“Something has got to be working in your body to get rid of that salt,” says Wainford, who heads a laboratory at the Whitaker Cardiovascular Institute. “We don’t know what that is. So if we don’t know what’s working in a healthy patient, how can we expect to fix something when it’s broken? That’s where I come in.”
Wainford specializes in the complex science of homeostasis—how the body maintains a stable balance of substances like sodium, glucose, and iron throughout its tissues and how this impacts blood pressure regulation. His research, funded by two grants from the National Institutes of Health’s National Heart, Lung, and Blood Institute, has already led to several insights about how our bodies regulate salt. His ultimate goal is to develop biomarkers for salt-sensitivity, which could lead to better diagnostics and treatment for high blood pressure.
“Something has got to be working in your body to get rid of that salt. We don’t know what that is.”—Richard Wainford
“We do see salt as a contributor to high blood pressure, but it also does a lot of other things,” says hypertension expert Haralambos Gavras, a MED professor of medicine. “It’s important to find out the mechanisms, that way, we can be more decisive in the treatments.”
One of the key organs for human homeostasis is the kidney, which helps regulate water, salt, and iron in the blood by choosing to excrete certain substances in the urine. Another key organ is the brain, which helps control the kidneys. Wainford studies the kidney-brain conversation by examining a particular signaling pathway, one that sends messages through certain molecules, known as gαi2 proteins, in the brain. When a person eats or drinks salt, signals along this pathway tell the brain to slow down communication from the brain to the kidney, and also for the kidney to increase the amount of salt in urine. The kidneys, left to their own devices and receiving constant communication from the brain, excrete less sodium in the urine. It’s a complicated chain of events, and Wainford wants to know exactly how this convoluted system comes together. So he studies how it works in rats. “In a simple sense, we study how rats pee,” says Wainford. “It’s a simple way to gain insight into the conversation between the brain and kidney.”
In one of his first experiments, Wainford worked with several breeds of salt-resistant rats, animals that can eat as much salt as they want with no effect on blood pressure. (Some rats are born that way, some bred.) “They maintain sodium balance—what goes in comes out. So they’re doing fine,” Wainford says. “But how is that happening? We wanted to know if this protein pathway—the gαi2 pathway—is involved. So we did the most simple experiment ever. I took these little rats that don’t get high blood pressure. We fed them salty diets for three weeks, and then we took their brains and looked at the expression of these proteins.”
“In a simple sense, we study how rats pee,” says Wainford. “It’s a simple way to gain insight into the conversation between the brain and kidney.”
He found a dramatic increase of this protein pathway in a brain region known as a “hot spot” for cardiovascular regulation. “It sends communications directly to the kidney and it sends communications directly to other brain centers,” he says. “And we were like, ‘Wow. That’s kind of interesting.’ So then we took it away.” In the same rats, he blocked the signal pathway by infusing the rats with a specific sequence of DNA that prevented them from making the gαi2 protein. Then he gave the animals salty food again, but this time they couldn’t get rid of the extra salt. As a result, they got high blood pressure.
“When healthy people eat salt, the activity of their central nervous system is turned down to get rid of it,” says Wainford. “When you remove this protein pathway in the brain of salt-resistant rats, that doesn’t happen. They’re not able to turn down the activity of the brain to that same extent.” Wainford, who published this research in Hypertension in 2013, believes this signaling pathway is one of several that affect the control of blood pressure. Other studies in humans have shown that a tiny defect in the gene for this protein—one single base pair off—is linked to hypertension. But his group is the first to find how it works: a clear molecular mechanism that regulates the communication between the brain and the kidney.
“It’s an interesting piece of work,” says Gavras, who cautions that this is still basic research and much more remains to be done. “It’s promising, but let’s see where it goes in the long run.”
Wainford followed this study with similar tests on salt-sensitive rats and with a more drastic measure of removing the animal’s renal nerves entirely, severing all communication between the brain and kidneys. Surprisingly, this kept the rats’ blood pressure low and seemed to have no other ill effects. (Medical device company Medtronic’s SYMPLICITY trials on humans have tried the same tactic of removing renal nerves from treatment-resistant hypertensive patients, with mixed results.)
“Clearly the impact of the renal nerves on blood pressure regulation in human subjects is complicated. I think the removal of the renal nerves is a very powerful technique; it just needs to be done right, and studied right, and in the right population,” Wainford says. “Ultimately, our goal is to more fully understand the mechanisms of how the brain and the kidney interact to regulate blood pressure. The more we understand that, the better we can treat patients.”
A version of this story originally appeared on the BU Research website.
This BU Today story was written by Barbara Moran. She can be reached at email@example.com.
SIG Pre-submission Process
The Shared Instrument Grant (SIG) program encourages applications from groups of NIH-sponsored investigators to purchase or upgrade a single item of expensive, specialized, commercially available instruments or integrated systems that cost at least $50,000. Types of instruments supported include, but are not limited to: X-ray diffraction systems, nuclear magnetic resonance (NMR) and mass spectrometers, DNA and protein sequencers, biosensors, electron and confocal microscopes, cell-sorters and biomedical imagers. See RFA here: http://grants.nih.gov/grants/guide/pa-files/PAR-15-088.html
The office of the Associate Dean for Research, BUSM will facilitate an internal SIG pre-submission process to foster collaborative proposals and increase the success rate for the University. This pre-submission process requires that applicants fill out an online form designed inform Dr. Antman, BUSM Dean and BUMC Provost of your interest in applying for an S10 Shared Instrumentation Grant.
The proposals will be routed to the Core Advisory Committee, who will assist the Associate Dean for Research, BUSM and the Provost with evaluating scientific merit and ensuring that highly-rated applications receive the appropriate level of institutional support to make them most competitive.
This process will:
- Identify the necessary level of institutional support needed for a competitive application.
- Identify any potential space and renovation needs ahead of the application.
- Help obtain access to equipment, or equipment loans, in order to generate additional data to strengthen the application if needed.
- Alert other members of the research community who may be important additions to the users group, and ensure transparency of the SIG process.
- Ensure that we do not have competing applications for similar equipment.
This process is not intended to prevent submission of applications, but to recognize that when multiple applications are being submitted, it may not be possible to centrally support all of them at a competitive level from the Provost’s or the Deans’ resources, providing the opportunity to identify alternative sources of funding.
If you are considering submitting a SIG in 2015, please fill out the SIG pre-submission online form as soon as possible. The internal submission deadline university-wide is March 9.
Members of the Medical Campus are invited to the Feb. 6 Cancer-focused Seminar Series (CFSS). The goal of the CFSS is to promote interaction and collaboration of cancer researchers across the Medical and Charles River campuses. Three talks will be presented at this seminar.
- Tracy Battaglia, MD, MPH, Battaglia Lab, “Repairing the Disconnect: Optimizing Cancer Care Delivery Through Patient Centered Research”
- Charina Ortega, Dominguez Lab, “Mining CK2 in Cancer”
- Kevin Chandler, PhD, Costello Lab, “Studying Posttranslational Modifications of Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) in Tumor Angiogenesis
What: Cancer-focused Seminar Series
When: Friday, Feb. 6, Noon-1:15 p.m.
Where: BUSM Instructional Building, L-110
Mark your calendar for future seminars March 6, April 3, May 1. All future seminars will take place noon-1:15 p.m. in Bakst Auditorium.