Receiving the Family Medicine Research Award (from left) is Stephanie Shaw and...
In appreciation for their dedication and patience during the unusually harsh winter, Deans Karen Antman, Sandro Galea and Jeffrey Hutter invited Boston University Medical Campus staff and faculty to the Equinox Celebration of Spring on Wednesday, March 18, in the Hiebert Lounge.
Photos courtesy David Keough (BUMC Educational Media) and BUSM Communications.
Boston University’s (BU) Biomedical Laboratory and Clinical Sciences (BLCS) Program and the Center for Regenerative Medicine (CReM) were awarded grants from the Massachusetts Life Sciences Center as part of a $17M package targeted for capital projects, equipment and supplies.
“We are delighted that both the Center for Regenerative Medicine (CReM) at Boston Medical Center (BMC) and Boston University School of Medicine as well as the Biomedical Laboratory and Clinical Sciences (BLCS) Program have received this honor from the Massachusetts Life Science Center,” said Karen Antman, MD, dean of Boston University School of Medicine and provost of Boston University Medical Campus. “Their investments in these programs will help patients with pulmonary hypertension, cystic fibrosis, and acute lung injury as well as provide students with the necessary equipment as they train for careers in the biotechnology field,” she added.
CReM was awarded $1.7 M to launch an expansive Lung Regeneration Initiative (LRI) as part of their Center for Regenerative Medicine. The goal of the LRI is the clinical application of recent BU-led discoveries in stem cell research, such as the treatment of lung diseases with personalized therapeutics, as well as the ultimate reconstitution of diseased lung epithelia in patients with emphysema. The LRI also aims to define and launch treatments for pulmonary fibrosis, pulmonary hypertension, cystic fibrosis and acute lung injury from inhaled pathogens.
The BLCS Program, which is offered by BU’s Metropolitan College in collaboration with the School of Medicine, received $180,000 in funding to enhance the quality of the training and add to the competencies of the students. The funding from MLSC will enable the BLCS program to obtain essential equipment: a small bioreactor, an HPLC protein chromatography unit and a small bench top fluorescence activated cell analyzer, as well as to implement an electronic laboratory information and management system to train students for the changing environment for record keeping in the biotech industry.
David Salant, MD, professor of Pathology and Laboratory Medicine at Boston University School of Medicine (BUSM) has been named as the 2015 recipient of The Donald W. Seldin Award. The Award recognizes excellence in clinical nephrology.
“Dr. Donald Seldin is one of the giants of Nephrology and his legacy is reflected in the successes of many of his former trainees that have gone on to become leaders themselves,” said Salant. “Receiving the Seldin Award is a singular honor.”
Salant, who also serves as chief, Section of Nephrology at Boston Medical Center, is supported by grants from the National Institutes of Health (NIH). He has conducted extensive research on immune disorders of the kidneys. “My research has focused on how the kidneys are damaged when our own immune system goes awry and makes antibodies that attack critical components of the kidneys,” he said.
Salant will receive the award at the National Kidney Foundation’s (NKF) Spring Clinical Meetings held March 25-29 in Dallas, Texas. The National Kidney Foundation (NKF) is the leading organization in the U.S. dedicated to the awareness, prevention and treatment of kidney disease.
The Federation of Pediatric Organizations (FOPO) has selected Boston University School of Medicine Professor and Chair Emeritus of the Department of Pediatrics Barry S. Zuckerman MD as the 2015 recipient of the Joseph W. St. Geme, Jr. Leadership Award. Dr. Zuckerman will receive this award April 25 at the Pediatric Academic Societies Meeting in San Diego.
FOPO is a national non-profit organization whose mission is to promote optimal health for children by uniting the efforts and expertise of its member organizations to accomplish shared goals.
Created in honor of St. Geme to recognize a pediatrician who is a role model for others to emulate as a clinician, an educator, and/or an investigator, recipients have had a record of broad and sustained contributions to pediatrics that have had or will have a major impact on child health. Most importantly, the award recognizes those individuals who have “created a future.”
Zuckerman is recognized for his tireless efforts to understand how social and environmental factors adversely impact children, and to create practical, scalable and sustainable tools that allow pediatric practitioners to intervene to improve developmental outcomes. In addition to his role at BUSM, Zuckerman is Professor of Public Health at Boston University School of Public Health. He has authored 250 publications, more than 130 of them peer-reviewed, and edited 12 books, including a leading book on Developmental and Behavioral Pediatrics, now in its third edition. His leadership and mentorship lead to the creation of Medical Legal Partnerships for Children, HealthLeads, Reach Out and Read and Healthy Steps, all of which focus on improving outcomes in our most vulnerable patients. This body of work has changed the face of pediatric practice, particularly in the places that care for our most vulnerable children.
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 email@example.com.
Deborah A. Frank, MD, BUSM inaugural Professor in Child Health and Well-Being, Pediatrics, has been named to the National Commission on Hunger by the U.S.Congress. Frank is director of the Grow Clinic for Children at Boston Medical Center (BMC) and founder and principal investigator of Children’s HealthWatch, a network of pediatric and public health researchers working to improve child health. A highly respected national authority, she has testified before both the United States and Massachusetts legislatures on the growing national problem of hunger and its effects on children. Learn more at https://hungercommission.rti.org/.
Deeper understanding of telomeres may lead to targeted cancer treatments
By a quirk of biology, every time an adult cell divides, a bit of DNA gets lopped off the end of the double helix. This seems like a recipe for disaster—imagine a crazed librarian ripping the last chapter off a book every time it got checked out. Soon, the book would be useless. So would truncated DNA, if not for structures called telomeres, long sequences of repetitive base pairs—the same meaningless TTAGGG over and over—that cap each end of our DNA. Every time a cell divides, it’s a bit of telomere that gets chopped off, rather than vital genes.
But biologists have long understood telomeres to be a double-edged sword. When they get too short, cells stop dividing. We see this as aging: hair turns gray, skin sags. But some cells are able to keep their telomeres long, effectively becoming immortal and dividing forever. Sometimes, the immortal cells become a cancer.
Now, scientists led by Rachel L. Flynn, a Boston University School of Medicine (MED) assistant professor of pharmacology and experimental therapeutics and medicine, have found a new way to kill certain cancers by targeting mechanisms of telomere elongation. The research, funded by the National Institutes of Health, the Foster Foundation, and the Karin Grunebaum Cancer Research Foundation, and published in the January 15, 2015, issue of Science, may lead to new therapies for certain rare and deadly cancers that often appear in children.
Cells that are able to lengthen their telomeres, and thereby divide indefinitely, use two known methods to do so. The more common is to use an enzyme called telomerase, which is active in embryonic stem cells but repressed as cells become specialized. The less common method, and the one Flynn studies, is called ALT, for alternative lengthening of telomeres. The ALT pathway is most prevalent in certain cancers, including pediatric osteosarcoma, a bone cancer, and glioblastoma, a type of brain cancer.
“In terms of the possible clinical applications, this research could be a game changer,” says Karen Antman, MD, provost of BU Medical Campus and dean of Boston University School of Medicine. “This exciting finding could allow us to target any cancer that uses the ALT pathway to maintain telomeres. Such cancers are often resistant to common treatment options and have a poor prognosis.”
The ALT pathway, though discovered almost two decades ago, is still poorly understood, says Flynn. “We know that ALT is a mechanism that relies on recombination—one telomere basically hijacks another and uses it to replicate and elongate itself,” she says. “But we didn’t know how the pathway was maintained until now.”
Flynn’s paper suggests how cancer cells may be able to maintain the ALT pathway—by depending on an enzyme called ATR kinase. This enzyme is what’s known as a “master regulator,” says Flynn. In a normal cell, it recognizes DNA damage when a cell is preparing to divide, and leads to either DNA repair or cell death. ALT cancer cells are constantly undergoing DNA repair at the telomere and are more reliant on ATR kinase activity than other cancer cells. Therefore, ATR promotes immortality by helping telomere elongation. Attack this enzyme, says Flynn, and you stop the cancer cell in its tracks.
“When you take ATR kinase out of the picture, it shuts down a whole chain of events,” says Flynn. “The cancer cell tries to promote telomere elongation, but it can’t, and the cell dies.”
There are several drugs already on the market that act as ATR kinase inhibitors, but none are used individually to treat these types of cancers. “The cool thing about these drugs is that the cancer cells actually die incredibly fast as opposed to just slowing down cell growth,” Flynn says. She also notes that since the drugs only affect cancer cells using the ALT pathway, normal cells should be left unharmed.
Flynn’s next step is to get the existing drugs into clinical testing for targeted use. She is working with a group at Massachusetts General Hospital who will test it on mice with glioblastomas. Eventually, she hopes, her work will lead to a new treatment for these deadly diseases.
“The dream is that this research will eventually give kids with devastating cancers an option for individualized treatment, something that will hopefully improve outcomes,” says Flynn.
This BU Today article was written by Barbara Moran. She can be reached at firstname.lastname@example.org.
A version of this story was originally published in BU Research.
Emelia J. Benjamin, MD, ScM, professor of Medicine at BUSM, professor of Epidemiology at BU School of Public Health, co-Principal Investigator of the Framingham Heart Study and attending cardiologist at Boston Medical Center, has been selected as the recipient of the prestigious 2015 American Heart Association (AHA) Paul Dudley White Award.
The award, named in honor of one of Boston’s most revered cardiologists, Dr. Paul Dudley White, a founding father of the AHA, is given annually to a Massachusetts physician who has made a distinguished contribution to the Association’s mission of building healthier lives, free of cardiovascular disease and stroke. Benjamin will receive the award at the Boston AHA Heart Ball on May 2. Last year BUSM faculty member Dr. Gary Balady, received the award.
Benjamin is an associate editor for Circulation, and she also volunteers as vice chair of the Heart Disease and Stroke Statistics annual publication. She is a current member of the Council Operations and the Research committees, and past chair of the Functional Genomics and Translational Biology Council, and the Genomics & Translational Biology, Epidemiology and Observational/Epidemiology Research Study Section. In 2012 and 2013 she received the AHA’s Women in Cardiology and Functional Genomics and Translational Biology national mentoring awards, respectively.
Benjamin focuses on cardiovascular genetic epidemiology, and has made major contributions in the areas of atrial fibrillation, inflammation, vascular function and echocardiography.
Med schools would remain separate, safety-net hospital would stay in place
Boston Medical Center, Boston’s “safety-net hospital” and the primary teaching hospital for the BU School of Medicine, is discussing a strategic partnership, including a potential merger, with Tufts Medical Center, the primary teaching hospital for Tufts University Medical and Dental Schools.
Karen Antman, dean of the School of Medicine and provost of the Medical Campus, stressed that any partnership or merger would not include the medical schools, which are parts of their respective universities.
Robert A. Brown, president of Boston University, says it is imperative that any partnership or merger maintain Boston Medical Center (BMC) as a premier academic medical center and as a safety-net hospital, fulfilling the hospital’s mission to provide exceptional care to the city’s vulnerable populations, regardless of insurance status or ability to pay. “BMC is a superb academic medical center and the city’s most important safety-net hospital,” Brown says. “If a partnership or merger can ensure that BMC continues to play both these roles in a stronger, sustainable way in the future, it is worth pursuing.”
Kate Walsh, president and CEO of Boston Medical Center, echoed Brown’s commitment to continuing to provide first-rate medical care for all. Walsh says conversations to date suggest that a strategic partnership may strengthen the missions of both medical centers and that “an affiliation that secures a long, bright future of continuing to provide exceptional care without exception would be of great interest to us.”
She says a partnership with Tufts Medical Center could have great potential benefits, including new options to serve patients, greater financial resources, and a larger referral network to attract new patients and better payments from insurers.
“Tufts Medical Center is our neighbor,” says Walsh. “We know them, we respect them, we share a common geography and a commitment to providing high-quality care to all patients. We also share a mutual commitment to our academic missions of teaching and research.”
Over the last 20 years, changes in health care models have made hospital partnerships and mergers a virtual requirement for a sustainable health care business, particularly in the Boston area. In 1994, Massachusetts General and Brigham and Women’s teaching hospitals teamed up to form Partners Health Care, which has since brought in several community hospitals around Boston. In a rival venture, Steward Health Care has, in the past few years, taken over 10 community hospitals as well at St. Elizabeth’s and Carney hospitals. Earlier this year, Beth Israel Deaconess Medical Center took control of Jordan Hospital in Plymouth and formed a joint venture with New England Baptist Hospital. Antman says many observers of Boston’s crowded health care arena consider a merger involving Boston Medical Center to be long overdue.
Similarly, changes in health care payments combined with cuts in research funding have hit academic medical centers particularly hard. An alliance between Tufts and BMC could produce efficiencies of scale, Antman says.
Walsh cautioned that while the two medical centers have much in common, “there is more work we need to do before we will know whether a partnership is the best option for our employees, and most importantly, our patients.”
A combination of the two medical centers could result in significant change for clinical faculty at both schools of medicine. Boston Medical Center currently has 724 physicians, including the clinical faculty at the BU School of Medicine, and Tufts Medical Center employs 500. BMC officials say any partnership involving the two hospitals would take years to accomplish, and that the medical center would continue to offer a full range of services.
“We do not underestimate the anxiety that this will create among our clinical faculty,” Brown says. “We also understand that the hospitals, and not the universities, control the outcome of any discussion. We will do all we can to provide support and advocacy on behalf of our clinical faculty during what will be a period of uncertainty.”
If the two hospitals merge, the two medical schools would remain separate, each with its own faculty, curriculum, and rotations, called clerkships. The merger would have no impact on the number of students enrolled at the BU Medical School or on the size of the medical sciences faculty who teach at the school. However, the consolidation may result in fewer hospital beds, which might reduce the number of clerkships and residency slots available to BU and Tufts Medical students in the consolidated hospital. Currently, 45 percent of BU medical students do their clerkships at BMC while 35 percent of Tufts medical students do theirs at Tufts Medical Center.
Antman says she does not foresee a shortage of clerkship opportunities for BU medical students. “We are affiliated with 20 other hospitals in the area,” she says, “and we have a program in place to identify even more clerkship and residency opportunities in Boston, and around the country.”
With more than 870,000 patient visits last year and more than 4,500 full-time staff, Boston Medical Center is the largest safety-net hospital in New England. Approximately 70 percent of BMC patient visits come from come from people who rely on government payers such as Medicaid, the Health Safety Net, and Medicare for their coverage.
Boston Medical Center struggled with changes to the health care business for years and only recently, under the leadership of CEO Kate Walsh, has it approached financial stability. In 2012, the hospital reversed three years of losses and posted a small but meaningful financial gain. At the same time, Moody’s Investor Service and Standard & Poor’s bumped up their ratings of the hospital from negative to stable.
“Kate Walsh’s excellent track record as our hospital leader gives us added assurance that any change is likely to be in the best interests of the hospital, the underserved, and those medical students and clinical faculty associated with the facility in the future,” Brown says.
Antman says she sees hope in successful mergers such as the 1998 partnership of New York Hospital and the Presbyterian Hospital, which created the 2,500-bed New York Presbyterian Hospital. That hospital, which has two distinct medical centers, Columbia University Medical Center and Weill Cornell Medical Center, serves as the primary teaching hospital for Columbia University’s College of Physicians and Surgeons and the Weill Cornell Medical College.
“In these initial discussions we are all looking forward to finding a new way to educate medical students in Massachusetts,” says Antman. “There is no reason we can’t work with our partners to create a better educational experience for our students.”
This BU Today story was written by Art Jahnke.
BUSM graduates MaryAnn Wilbur, MD, MPH (MED ’11, MPH ’11), and James Yeh, MD, MPH (MED ’10), have been chosen for prestigious New England Journal of Medicine (NEJM) editorial fellowships. With more than 600,000 readers in 177 countries, NEJM is the most widely read and cited general medical journal in the world and has a rigorous peer-review and editing process. The yearlong program involves fellows in the day-to-day editorial activities of the journal, work on journal articles and an independent project.
“The fellowships help us inject new ideas into the NEJM,” says Jeffrey Drazen, MD, editor-in-chief of the NEJM. “We are interested to hear each fellow’s fresh perspective, and we hope their relationships with us continue well after their fellowships end.”
Chief resident in obstetrics and gynecology at Johns Hopkins Hospital, Mary Ann Wilbur served as the case manager for the Grow Clinic at Boston Medical Center, BUSM’s primary teaching hospital,
before being accepted to medical school. “For me, medicine is the perfect marriage of science and advocacy, and BUSM was the natural choice for my medical education,” she said. “I had been working on campus at BMC, which cares for the underserved populations of Boston and shares my personal mission.” As a co-founder of the BU Advocacy Training Program, Wilbur also completed a Master’s in Public Health, “because I recognized the importance of understanding the social determinants of health and wanted a framework on which to build when advocating for marginalized populations.”
A co-author of a number of published articles while a medical student, Wilbur learned about the NEJM fellowship from doing a BUSM elective at the journal. “NEJM is a prestigious periodical, and I hope to learn more about how editors review medical literature, a key to successful publishing in the future,” she says. “I also am very interested in the NEJM Perspective articles, which strongly influence the politics of medicine and will help facilitate my career as a physician advocate.” After completing the fellowship, Wilbur plans to stay in Boston to focus on women’s health while caring for the city’s underserved populations.
Yeh practices urgent care medicine at Brigham and Women’s Hospital, Boston, and is a hospitalist on the inpatient medicine service. He completed his internal medicine residency at Cambridge Hospital and is completing a research fellowship in general internal medicine through the Harvard Medical School (HMS) faculty development program. He also is completing a Master’s in Public Health in Clinical Effectiveness at Harvard School of Public Health.
He is the author and co-author of a number of research articles and book chapters, and editor of several books. Yeh serves as deputy editor for the Harvard Public Health Review and as an ad hoc manuscript reviewer for the Journal of General Internal Medicine, contributing editor to the DynaMed EBM Journal, and was an abstract reviewer for the American College of Physicians Annual Meeting 2010-2013.
“I am interested in evidence-based medicine and knowledge translation, and I hope to gain insights in how a medical journal can help communicating medical research into clinical practice,” says Yeh of his participation in the NEJM fellowship. He also is interested in understanding the effectiveness of the communication process about drug effectiveness and safety, and in the FDA’s regulatory policies and drug risk communication. The recipient of HMS awards for excellence in teaching, he plans to continue in academic medicine because of his love of teaching and research along with patient care.
“The New England Journal of Medicine plays a pivotal role in communicating many of the best biomedical research studies as well as framing many medical policy positions,” says BUSM Dean Karen Antman, MD. “Our recent graduates, Drs. Wilbur and Yeh have earned this important opportunity to broaden their perspective on medical communication.”