Engaging Patients to Improve Health Care Outcomes
How can engaged patients improve health care? BUSM's Suzanne Mitchell, MD, and other...
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View BUSM Commencement Pics on Facebook
On Saturday, May 17, members of the BUSM Class of 2014 gathered to celebrate their graduation from medical school. Congratulations, Grads! View the pics on Facebook
Graduates Welcomed to Medical and Scientific Community
The 167th Boston University School of Medicine commencement opened with an academic procession of 300 members of the faculty lining up on either side of the Class of 2014 to welcome them into the community of scientists and physicians. The ceremony, held at the Agganis arena on May 17, was a celebration of achievement and commitment to medical research and caring for patients.
“We gather together today to publically recognize and celebrate the credentials that these degree candidates have earned, a major life transition,” said Dean Karen Antman, MD. “I speak for the faculty in saying that it has been a great privilege to work with you. You are smart and committed, resilient and adaptive.”
The degrees earned by the Class of 2014 included 52 PhDs, 157 MDs, 12 MD-PhDs, 10 MD-MPHs, and six graduates who received an MSc.
“It has been said that ‘life is what happens when you are otherwise making plans,’” said U.S. Assistant Secretary of Defense for Health Affairs Jonathan Woodson, MD, who delivered the commencement address. “I have found this to be true time and again, and it expresses the need in life to expect the unexpected. Each of you should be prepared to negotiate around obstacles even as you keep your eye on the prize or the long range goals you have set for yourself. It is important to understand that deviations are the friction points in life when we learn the most about ourselves and we grow.
Woodson asked the parents of the graduates to stand to be recognized for their support and dedication that helped make their children’s accomplishments possible.
Speaking for her fellow doctoral students, Ariana Harris, PhD, noted, “To solve the mysteries of the world, we need each and everyone one of us to contribute. In a little while we will received our academic hoods and you will hear the titles of our individual projects, getting a sense of how different they are. This is what makes the scientific community amazing. There is so much to learn and so many of us are eager to figure it out. I am confident that whatever careers we pursue as individuals, our thirst for knowledge will continue. We use our scientific training every day. We search for logic, reason and evidence that support our thoughts and beliefs.”
Referring to the white coats he and his classmates received upon entering BUSM, Brian Curry, MD, speaking on behalf of the medical students, said, “We received these as a symbol of our induction to a calling. We didn’t realize it at the time, they also symbolized the granting of a very special kind of power. One that, just like our white coats themselves, we have spent the better part of four years clumsily trying to grow into and will likely continue to do for the rest of our careers. My message to you, BUSM class of 2014, is simply this: Earn this power. Earn it, but recognize we will never own it. We only can ever be responsible stewards of this power our patients have entrusted to us. Though today marks the retiring of these short white coats, we should never allow ourselves to get fat and happy with the notion that we have somehow grown into them. We must earn it anew every day, with every patient, always.”
Register for the John McCahan Medical Campus Education Day
Boston University’s Schools of Medicine, Public Health, Dental Medicine and the Division of Graduate Medical Sciences are proudly sponsoring the John McCahan Medical Campus Education Day on Thursday, May 22, 8:30 a.m.-3:30 p.m. in the BUSM Instructional Building, Hiebert Lounge 14th Floor.
“Education Day is a fantastic opportunity to meet and network with innovative educators from across the entire medical campus,” explains BUSM Gross Anatomy Course Director Ann Zumwalt, PhD, who also serves as chairman of the event planning committee. ”The event showcases creative educational initiatives and is consistently inspiring and invigorating for BUMC educators.”
The purpose of the event is to showcase and enhance educational innovations, scholarship and research across the Boston University Medical Campus. All faculty, students, residents, fellows and staff of BUMC are invited to attend.
Register online: http://www.bumc.bu.edu/jmedday/ Registration by May 22 is required for workshops and lunch.
Program Highlights
Keynote Lecture: (8:45 a.m.)
The Art and Science of Giving Feedback
Carole Pfeiffer, PhD
University of Connecticut Health Center
Dr. Pfeiffer is a Professor of Medicine and a sociologist who has worked in medical education for three decades. She is the Director of the Clinical Skills Assessment Program at the University of Connecticut School of Medicine and was a founding member of the Association of Standardized Patient Educators. She has a particular interest in communication skills in the clinical encounter.
Poster Session: Posters focus on themes of educational innovations, research and technology. Oral presentations and awards will be given for outstanding student, fellow/resident and faculty abstracts
Luncheon: Pre-registered attendees will be provided lunch. Register
Faculty Workshops: Pre-Registration required. Participants will learn about educational strategies, innovations, research and scholarship by attending the interactive workshops. See workshop details and registration online.
Contact: For more information, contact Liza Young, 638-4799 or lizamil@bu.edu
John McCahan Medical Campus Education Day
- Thursday, May 22
- 8:30 a.m.-3:30 p.m.
- BUSM Instructional Building, Hiebert Lounge 14th Floor.
Free Fitness Center-based Exercise Referral Program Among Women with Chronic Disease Risk Factors Not Well Utilized
Eliminating financial barriers to a fitness center as well as providing physician support, a pleasant environment and trained fitness staff did not result in widespread membership activation or consistent attendance among low income, multi-ethnic women with chronic disease risk factors or diagnoses according to a new study from Boston University School of Medicine. The findings, published in Journal of Community Health, is believed to be the first study of its kind to examine patient characteristics associated with utilization of community health center- based exercise referral program.
Currently, fewer than half (47.3 percent) of Americans meet expert recommendations of 150 minutes per week of moderate-intensity exercise or 75 minutes per week of vigorous-intensity exercise. Women are less likely than men to meet guidelines for physical activity. Certain subpopulations are at elevated risk for both inactivity and CMD, including Hispanics, African Americans and those below the poverty level.
Adult female patients of a community health center with an affiliated fitness center, were included in the study if they received a referral to the fitness center from their primary care provider. Demographic and medical information was abstracted from their medical chart and fitness records were abstracted to measure activation of a fitness center membership (creation of an account denoting at least an initial visit) and utilization over time.
The researchers found less than half of the women activated their memberships (40 percent), although Black/African Americans women and those with higher numbers of co-morbidities were more likely to activate. In addition, only a small subset–10 percent of women who activated their memberships (0.4 percent of the total referred sample)–achieved three-month participation levels consistent with cardiometabolic disease (CMD, including heart disease, hypertension, hyperlipidemia, Type 2 diabetes) risk reduction. Nonetheless, average visits per month declined from the beginning to the end of the free 3-month trial membership period.
“Despite providing free access to a fitness center and its staff, the number of women utilizing this service was highly variable,” explained corresponding author John Wiecha, MD, associate professor of family medicine at BUSM. “Our observations are consistent with findings from the United Kingdom, where a recent systematic review found that exercise referral “uptake” (attendance at an initial consultation) by participants varied from 28 to 100 percent and “adherence” (signifying participation in at least 75 percent of all sessions) from 12 to 93 percent,” he added.
According to Wiecha, these findings suggest that program design may benefit from developing activation, initial participation, and retention strategies that address population-specific barriers and integrate credible behavioral change strategies. “Significant public health gains could be realized by increasing physical activity among populations at high risk of chronic disease, and additional research is warranted to develop effective models in the U.S.,” said Wiecha.
Cancer’s Potential On-Off Switch
Sibaji Sarkar
A team of Boston University School of Medicine (BUSM) researchers have proposed that an “on and off” epigenetic switch could be a common mechanism behind the development of different types of cancer. Epigenetics is the phenomena whereby genetically identical cells express their genes differently, resulting in different physical traits.Researchers from the Boston University Cancer Center recently published two articles about this in Anticancer Research and Epigenomics.
The current paradigm states that cancer develops from environmental and genetic changes to cancer progenitor cells. These changes are the result of mutations, exposure to toxic substances or hormonal imbalances.
Cancer progression is extremely complex, however. It also is well known that new mutations and the activation of more cancer causing genes occur throughout the development and progression of cancer.
“If we believe that everything in nature occurs in an organized fashion, then it is logical to assume that cancer development cannot be as disorganized as it may seem,” said Sibaji Sarkar, PhD, instructor of medicine at BUSM and the articles corresponding author. “There should be a general mechanism that initiates cancer progression from predisposed progenitor cells, which likely involves epigenetic changes.”
The existence of this epigenetic switch is indirectly supported by the fact that tumors develop through different stages. When cells rapidly grow during cancer progression, they become stuck in their current stage of development and their cell characteristics do not change. This is the reason that there are so many types of leukemia—the characteristics that a leukemia cell possesses when it begins to rapidly grow and expand are the characteristics that it will keep until the rapid growth stops.
Shannon Byler
“If we believe that all of the irreversible changes, mutations and effects of carcinogens make cells rapidly grow, then the mechanism that allows cells to stop growing and assume new changes in character must be of great importance,” added Sarkar. “The study of cancer progression is key to understanding how cancer cells continue to differentiate.”During cancer progression, there are different stages of rapid growth and differentiation. The control that allows for this switch between growth and differentiation can only be achieved through reversible mechanisms, such as epigenetic changes.
Sarkar and colleagues have previously proposed that epigenetic changes are involved in cancer progenitor cell formation and cancer progression. They also believe that epigenetic changes have the ability to control rapid growth and change of characteristics (different grades/types of tumors).
Sarkar compares the stages of cancer growth to a rocket orbiting in space – that is, that an object within an orbit continues to circle a given path, until it is given a signal (or additional fuel) to propel itself into a further orbit. This comparison can be made for cancer progenitor cells and epigenetics. A specific cell continues to grow at a certain stage until it is given a signal – in this case, an epigenetic switch – that propels it to differentiate into a new orbit, or further differentiated cell.
“While the specific details of the epigenetic code that regulates these changes has not been discovered, the fact that we have a possible explanation for the reversible and ever-changing characteristics for cancer progenitor cells is very exciting,” said Sarkar. “Future epigenetics findings hold the key to develop drugs which could possibly kill cancer progenitor cells to reduce cancer relapse and drug-resistant cancer cells.”
Shannon Byler, who served as the first author for both articles, is a student at Boston University. Other BU student co-authors of the Anticancer Research article are Sarah Goldgar, Sarah Heerboth, Meghan Leary, Genevieve Housman and Kimberly Moulton.
Now Available, Aceso: Journal of the BU School of Medicine Historical Society
Aceso Spring 2014 issue
The BUSM Historical Society is proud to announce publication of Volume II of Aceso: Journal of the Boston University School of Medicine Historical Society.
The BUSM Historical Society mission is to expose students and the BUSM community to the rich history of the School, Boston Medical Center, medicine in Boston, and the medical profession in general. By exploring how the landscape has changed and the profession has evolved, and introducing people and innovations that helped create modern medicine, the society offers perspective and inspiration for students to carry throughout their careers.
Aceso: Journal of Boston University School of Medicine Historical Society is named for the Greek goddess Aceso and comes from the Greek word akéomai meaning “to heal.” Aceso represented the healing process. Unlike other gods, she personified medicine from the patient’s perspective as a process involving both the ill person and the physician. Aceso was involved in overall care and the recognition that healthcare and well-being took time and was an active process.
“This aspect of healing is in striking accord with the BUSM mission and BU CARES educational philosophy,” says Michael Sherman, BUSM ’15, Aceso founder and editor-in- chief. “In our journal we hope to highlight medical history and all of its manifestations. With Aceso, it is our intent to awaken the reader to the common ground we all share. By exposing readers to the vast experience that the humanities offer, we will provide a better understanding of our place in medicine and society.”
May 13 Fifth Annual Lynne Stevens Memorial Lecture
“Trauma Informed Services: Implications for Healthcare Providers and Systems”
Carole Warshaw
Carole Warshaw, MD
Director, National Center on Domestic Violence, Trauma and Mental Health
Executive Director, Domestic Violence Mental Health Policy Initiative
Tuesday, May 13
Noon-1 p.m.
BUSM Instructional Building, L-110
This annual memorial lecture is in honor of Lynne Stevens, LICSW, BCD (1946-2009), the director of the Responding to Violence Against Women Program and an Assistant Professor in the Department of Family Medicine. She was a clinician, activist and researcher who worked locally, nationally, and internationally, specializing in evaluation of the quality of care offered to women who were victims of violence.
Attendees are cordially invited for lunch at 11:45 a.m. and a Q & A discussion from 1-2 p.m. with Dr. Warshaw following the lecture.
Study Shows that Impulsivity is Risk Factor for Food Addiction
Have you ever said to yourself that you would only have a handful of potato chips from the bag then, minutes later, realized you ate the whole thing? A recent study shows that this type of impulsive behavior might not be easily controlled – and could be a risk factor in the development of food addiction and eating disorders as a result of cellular activities in the part of the brain involved with reward.
The research, published online in Neuropsychopharmacology, was led by Boston University School of Medicine (BUSM) and conducted in collaboration with the University of Cambridge in the United Kingdom. It also points out the common mechanisms involved between drug and food addiction. (Pictured L-R: Dr. Valentina Sabino, Cassie Moore, Dr. Clara Velazquez, Toni Ferragud and Dr. Pietro Cottone)
Research has shown that people with eating disorders and obesity are known to be more impulsive than healthy people. For example, they may be more likely to blurt out something that they later regret saying or to start an activity without thinking through the consequences. However, it was unclear whether the impulsivity existed before the dysfunctional eating behavior or if developed as a result of it.
BUSM researchers attempted to answer this question by measuring the inability to withhold an impulsive response in experimental models that were exposed to a diet high in sugar daily for one hour. Models shown to be more impulsive rapidly developed binge eating, showing heightened cravings and the loss of control over the junk diet (measured as inability to properly evaluate the negative consequences associated with ingestion of the sugary diet). Conversely, models shown to be less impulsive demonstrated the ability to appropriately control impulsive behavior and did not show abnormal eating behavior when exposed to the sugary diet.
Interestingly, the impulsive models showed increased expression of a transcription factor called Delta-FosB in the nucleus accumbens, an area of the brain involved in reward evaluation and impulsive behavior, indicating a potential biological component to this behavior.
“While impulsivity might have aided ancestors to choose calorie-rich foods when food was scarce, our study results suggest that, in today’s calorie-rich environment, impulsivity promotes pathological overeating,” said Pietro Cottone, PhD, co-director of the Laboratory of Addictive Disorders and associate professor of pharmacology and psychiatry at BUSM.
“Our results add further evidence to the idea that there are similar mechanisms involved in both drug and food addiction behavior,” said Clara Velazquez-Sanchez, PhD, postdoctoral fellow in the Laboratory of Addictive Disorder and first author of the study.
Other contributors to the study include Valentina Sabino, PhD, co-director of the Laboratory of Addictive Disorders and assistant professor of pharmacology and psychiatry at BUSM; Antonio Ferragud, PhD, and Cassie Moore from BUSM; and Barry Everitt, ScD, from the University of Cambridge, UK.
Research included in this study was supported in part by the National Institute on Drug Abuse, the National Institute of Mental Health, the Peter Paul Career Development Professorship, the McManus Charitable Trust, and Boston University’s Undergraduate Research Opportunities Program (UROP).
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A Day to Give
24-hour fundraising drive for BU Annual Fund on April 30
The Boston University community includes 300,000 alumni and 29,000 parents around the globe, along with 30,000 students and 9,000 faculty and staff members. On Wednesday, April 30, the University will ask that far-flung group to come together for 24 hours—on campus and online—for the first-ever Giving Day.
The 24-hour fundraising drive will benefit the BU Annual Fund, which provides resources for the University’s schools, colleges, and athletic teams, as well as for scholarships and other initiatives. BU community members are encouraged to donate, participate in on-campus activities, and spread the word through social media. Donors can give to their choice of program or area within BU. But time is limited: Giving Day starts at 12:01 a.m. EDT on April 30, and ends at midnight EDT.
“This is an opportunity for alumni, students, parents, and friends to make a huge difference in a short period of time, uniting around a common goal,” says Dan Allenby, assistant vice president for Annual Giving. “Giving Day is all about participation; giving back to what made, or makes, your BU experience so great, supporting future students, and building community.”
To increase the impact of Giving Day, and to encourage and reward the philanthropy of other participants, BU trustee Stephen Karp (CAS’63) has issued a challenge: He will match, dollar for dollar, any gift of less than $1,000, and the first $1,000 of each larger gift.
To take advantage of the matching challenge, the Class Gift Committee is encouraging seniors to give to the Class Gift Campaign on Giving Day. “This is a great opportunity for students to take action and demonstrate why they love BU,” says Markiesha Ollison (CGS’12, SMG’14), the committee’s marketing chair. “I’m excited to interact with alumni. To students, alumni seem like distant cousins. But on a day like this, they seem more like brothers and sisters.”
Alumni, parents, and friends around the world are invited to get involved through social media. “It’s a time for alumni to reflect on the meaningful connection they have with the BU community,” says Mark DiCristofaro (CGS’06, COM’08), a film and TV producer based in Los Angeles. “For me, those connections have become clearer down the line.”
DiCristofaro plans to donate on Giving Day, in honor of those connections, and to say thank you to those whose contributions enriched his student experience. “At the College of General Studies and the College of Communication, enhanced facilities and equipment were donated by parents and alumni, and those had a direct effect on my BU experience,” he says. “And as a member of the golf team, I benefited from contributions from team alumni, which offset the cost of our travel and gear.”
On-campus activities
Local alums can be a part of Giving Day across the Charles River Campus. At stations set up in the School of Management lobby, on Marsh Plaza, at the GSU Link, and at FitRec, student volunteers and BU staff members will answer questions, take donations, give away prizes, stage contests, and take photos and shoot videos to share online, so that alumni, parents, and others who aren’t on campus can be part of the fun for the day. And don’t forget to visit the photo booth on Marsh Plaza.
Social media activity
Participants can use the hashtag #BUGivingDay on Facebook, Instagram, Twitter, and Vine posts to be part of the conversation—and to check out what others are saying about Giving Day. To show your support, switch your cover and profile photos to the Giving Day–branded versions available on the Giving Day website. After you donate, tell the community why, by posting your own video, photo, or testimonial using the #WhyIGivetoBU hashtag. Throughout the day, the BU Alumni Association will share #WhyIGivetoBU posts, and send out updates and bonus challenges, including opportunities to earn extra funds for individual schools and colleges.
Giving Day starts at 12:01 a.m. EDT on April 30, and ends at midnight EDT. Donate on April 30 here. Questions about Giving Day? Email givingday@bu.edu, call 800-447-2849, or visit the website. Learn more about all of the great reasons to give to BU here.
This Bostonia story was written by Alyce Nicolo (COM’07)
Gerard Doherty, MD, Elected President of American Association of Endocrine Surgeons
Gerard Doherty
Gerard Doherty, MD, chair of the Department of Surgery at Boston University School of Medicine (BUSM) and chief of Surgery at Boston Medical Center (BMC) and has been elected as President of the American Association of Endocrine Surgeon (AAES). He will serve as President through 2015.
As president, Doherty will preside at council assemblies and the annual members’ assembly. He will appoint members to all committees, serve as an ex-officio member of each, appoint successors to open positions, and deliver the 2015 Presidential Address.
Endocrine surgery is the discipline of surgical management of endocrine disorders, including the understanding of the disease process, and comprehensive care of surgical endocrine disease of the neck and abdomen. The AAES is dedicated to the science and art of endocrine surgery, and maintenance of the highest standards in clinical practice.
“Being chosen by my colleagues to fulfill this role is a distinct honor. The AAES has been my professional home throughout my career, and I admire the many achievements that we have made as a group to improve the care of patients, to advance the field, and to train the next generation of practitioners.”
Doherty’s clinical focus is endocrine oncology and comprises surgical diseases of the thyroid, parathyroid, endocrine pancreas and adrenal glands, as well as the surgical management of multiple endocrine neoplasia (MEN) syndromes.
Prior to coming to BUSM and BMC in 2012, Doherty spent a decade as chief of General Surgery at the University of Michigan Health System. He is the immediate past-president of the Michigan Chapter of the American College of Surgeons and has held multiple leadership positions in national and international professional groups, including the Board of Directors of the American Thyroid Association.
A graduate of Holy Cross and Yale School of Medicine, Doherty completed his residency at the UC-San Francisco, including Medical Staff Fellowship at the National Cancer Institute. He joined the faculty at Washington University School of Medicine in 1993 and became professor of Surgery there in 2001.
Regenerative Medicine Generates Hope
Egos in BU center take a backseat to sharing, progress, and promise
In the video above, CReM founders Darrell Kotton, Gustavo Mostoslavsky, and George Murphy discuss how they use iPS cells to study disease development, conduct drug screenings, and eventually to correct genetic mutations, with the goal of producing healthy tissues and organs for transplantation. Photo by Jackie Ricciardi
“Our mission is to decrease the burden of human suffering on the planet, help patients, and advance new knowledge.” —Darrell Kotton
With the motto Advancing Science to Heal the World the BU stem cell scientists who founded the Center for Regenerative Medicine (CReM) could be pegged as starry-eyed idealists or scientific superheroes. Or perhaps a bit of both.
CReM codirectors Darrell Kotton, Gustavo Mostoslavsky, and George Murphy have established themselves as venturesome researchers who are willing to share their discoveries with almost anyone. And they do it for free—bucking the prevailing trend to patent, publish, and protect scientific breakthroughs. The trio’s “open source biology” is just one of the things they teach to the next generation of stem cell researchers at CReM.
Open source biology can seem antithetical to scientists in an extremely competitive field. One young researcher training at CReM recently approached Kotton, a School of Medicine professor of medicine, seeking advice on how to answer an outside request for a vial of stem cells that took several years and hundreds of thousands of dollars in federal grants to develop. The obvious answer, the trainee assumed, was to tell the researcher to wait until the discovery was published.
Kotton saw it differently. “Our mission is to decrease the burden of human suffering on the planet, help patients, and advance new knowledge,” Kotton reminded him. “If this competitor of ours has the same goal, then we’re obligated to share this cell vial with them, because that’s going to achieve our mission.…which is not to get credit and to stroke our egos.”
A naïve response? “Here’s the thing that nobody talks about,” says Kotton. “If you behave in this way, people in our community quickly get the idea that the BU-BMC CReM are the good guys of science. At some point, the equation gets so lopsided that people almost feel embarrassed that they’re not sharing with you and so they tell you stuff, and the whole field starts to move forward.”
In fact, CReM founders say that increasing numbers of researchers are asking CReM to collaborate on grants, and foundations have begun to recognize that funding a CReM project very probably means that resulting knowledge, expertise, and reagents will be shared with other academic or nonprofit laboratories without restriction or exclusivity.
“I can’t emphasize enough how unique that was for the community,” says Mostoslavsky, a MED assistant professor of gastroenterology. “We have dozens of emails that testify to that, saying, ‘I must tell you this is the first time in my 30 years of being a scientist that someone replied and sent me stuff the same week of asking for it.’”
Still, Mostoslavsky says, there is a “fine balance that is not easy to achieve” between freely sharing their work and protecting it once research has advanced to the clinical stage. “That is a major undertaking,” he says. “It’s very expensive—no academic institution can support it—so we do need a company to move forward,” which also means they’ll need patented protection of intellectual property.
Stem cell scientists Gustavo Mostoslavsky (from left), Darrell Kotton, and George Murphy founded the Center for Regenerative Medicine with the motto: Advancing Science to Heal the World. Photo by Jackie Ricciardi
Scientific soul mates
Kotton, Mostoslavsky, and Murphy met as Harvard postdoctoral fellows in the lab of renowned stem cell scientist Richard Mulligan, who is famous for his rigorous research and forthright style of mentorship. “It was more of a sink-or-swim methodology, where you really had to prove yourself,” says Murphy, a MED assistant professor of medicine. “Coming out of there, we were battle-tested and bombproof.”
The three gravitated toward each other as “scientific soul mates,” Mostoslavsky says. Long after fellow researchers had left the lab, they would gather for late-night pizza and animated discussions, probing one another’s data to test the strength of their work. “We were each other’s worst critics as well as biggest fans,” Kotton says. It was around that time that they began toying with the idea of conducting science their way—in a meticulous, yet open and collegial manner.
After completing his Harvard fellowship, in 2006 Kotton returned to MED, where he had done a fellowship previously, to launch his own lung stem cell lab. He confesses to “putting psychological pressure” on his friends to follow him to BU, and he is not at all unhappy that it worked. In 2008, Mostoslavsky came aboard, creating his own lab. He was followed soon after by Murphy.
Several events conspired to launch CReM on the Medical Campus. The founders discovered a strong advocate in David Coleman, Wade Professor and chair of the MED department of medicine, who emphasized the importance of a robust research presence on the Medical Campus. Kotton, Mostoslavsky, and Murphy had followed closely the rapid advance of stem cell biology since 2006, when scientists at the University of Kyoto developed induced pluripotent stem cells (iPS) by reprogramming an adult differentiated cell. A tinkerer at heart, Mostoslavsky was fascinated by the Kyoto process, but felt he could go one better. In 2008, he developed a more efficient tool to generate stem cells, called the stem cell cassette (STEMCCA). BU patented the tool, which has become industry standard.
In 2010, with STEMCCA and multiple publications under their belts, the trio established a virtual Center for Regenerative Medicine, with its own website, seminar series, and iPS cell bank carrying branded labels. All this was accomplished while working in separate labs, with Murphy’s and Mostoslavsky’s divided by floors within a building, and Kotton’s located across the street.
As the number of stem cell biologists, physician-researchers, and biomedical engineers grew on both BU campuses, the affectionately labeled CReM brothers felt it was time to pitch a physical center to BU President Robert A. Brown, who firmly backed the idea. Boston University and Boston Medical Center invested jointly in the endeavor, and in November 2013, CReM opened in its newly remodeled space on the second floor of 670 Albany Street.
In the video above, CReM founders discuss how they use induced pluripotent stem (iPS) cells in their labs.
Clinical trial in a test tube
CReM’s mission is to advance stem cell research and regenerative medicine for the treatment patients, in particular those at BMC, with diseases such as cystic fibrosis, emphysema, sickle cell anemia, and amyloidosis. Investigators collect blood or skin cell samples, usually from patients at the Alpha-1 Center, the Center of Excellence in Sickle Cell Disease, and the Amyloid Center, and reprogram them into iPS cells.
“Any cell can be reprogrammed,” says Mostoslavsky. “It’s a true biological rejuvenation. The cells really go back in time.” Researchers now have the ability to coax iPS cells—which uniformly carry a patient’s genetic mutations—into their desired cell line, such as lung, liver, or blood. (CReM’s iPS cell bank stores at least 13 such cell lineages.) Mostoslavsky says the resulting cells are “still a work in progress,” compared to those found in nature, but the process allows researchers to watch how an iPS-derived lung cell develops the early stages of cystic fibrosis. What took years to unfold in a patient takes days in the lab.
CReM investigators can screen drugs against patient cell lines to determine which medications are most effective for a specific genetic mutation—the “clinical trial in a test tube,” as Murphy calls it. “In theory,” he says, “you could develop therapies that are molded specifically for a particular patient with a particular disease.”
Developmental biology and drug screenings are now CReM’s bread and butter, but its founders keep in mind what they call their long-term “Apollo projects,” such as genetically engineering iPS cells to correct patients’ mutations. The resulting healthy cells could be cultured and multiplied to regenerate a transplantable organ that wouldn’t be rejected by the patient’s body. That particular medical breakthrough would mean Kotton’s wife would need to look for a new job. Camille Kotton is a transplant infectious disease physician at Massachusetts General Hospital, and Kotton jokes that his “goal is to put her out of business.”
Kotton has been collaborating with a team of MGH researchers using a technology called lung decellularization and recellularization, which strips the organ of its cells and repopulates it with genetically engineered copies that lack the patient’s original mutation. Theoretically, the reprogrammed cells could multiply, fill the lung’s scaffolding, and someday be used for transplantation.
Kotton, who thinks it will be possible eventually to re-create lungs via 3-D printing technology, is collaborating on this with Christopher Chen, a College of Engineering professor of biomedical engineering.
Meanwhile, Murphy dreams of brewing blood. “The human body makes 2.5 million red blood cells every second of every day,” he says. “How does one contend with that from a research platform?” He thinks they will be able to “harness molecular cues” that exponentially increase the amount of artificial blood they can produce in vitro. Such a discovery could eliminate the need for blood donation in the United States and—even more urgent—in Third World countries, where the practice is not widely accepted.
Another of Murphy’s Apollo projects is boutique blood, or the development of small batches that could be produced for people who suffer from sickle cell anemia or the blood disorder beta thalassemia and require transfusions of rare blood types.
CReM technician Ryan Mulhern and Clarissa Koch (MED’16) pipette cell samples under ventilation hoods in CReM’s high-tech facilities. Photo by Jackie Ricciardi
Researcher as healer
In the past four years, word has spread about the CReM founders’ work to the point that as well as the emails from potential collaborators who want access to their work, they now get email from patients who either suffer from the particular disorders they study or have children who do.
The latter are heartrending. “‘We will sign whatever you want us to sign, and we don’t care how experimental your platform is, we would still like to use it to save our kid,’” Murphy recalls reading. He explains that although his team is working hard to find new treatments, right now there are no current stem cell therapies for their child’s condition. Asked when they might be available, he replies, “‘Sooner than you think.’ That’s vague, but it’s hopeful. And it also is the way that we see things.”
Kotton likes to tell a story that underscores CReM’s potential. He and his colleagues were approached about a child who suffered from severe cardiac arrhythmias. Their labs developed iPS cells from the boy’s skin cells and differentiated them into heart muscle cells, then sent them to researchers in New York City, who screened them against a series of drug regimens until they found a winning combination. After three months on the medication, the boy’s arrhythmia decreased from 100 incidents per month to zero.
“This success story represents, I believe, the first human being on planet Earth to be helped by the new iPS cell technology,” Kotton says. “If there is one patient who can benefit from these cells, then surely there are myriad more for generations to come.”
This BU Today story was written by Leslie Friday. Videos by Joe Chan
