The Massachusetts Medical Society has announced its selections of MMS Scholars for 2015. A...
By Lisa Brown
In a review article recently published in the journal Clinical and Translational Medicine, researchers from Boston University School of Medicine (BUSM) shed new light on the underlying processes of tumor metastasis and highlight the role of epigenetics in this process. By comparing embryogenesis with cancer metastasis they hypothesize that reversible epigenetic events regulate the development of different types of metastatic cancers. They also describe that the surrounding cells of the tumors (stromal cells) play a significant role in this process.
The BUSM researchers support the hypothesis that metastasis is more of a gradual process, leading to a heterogenic tumor population with cells of various epigenetic and differentiation statuses. They propose that cancer progenitor cells slow their growth while differentiating into more metastatic forms and then resume rapid division once the cells have metastasized to certain state or grade. Similar processes again take place when that grade of metastatic cancer changes to another grade.
As this process is not a one-time event during tumor metastasis, the slowing of growth and increase in differentiation must happen many times. Once the desired grade is achieved, the reverse process needs to take place. Epigenetics is what allows the cells to transform reversibly. In accordance with this hypothesis, metastasized tumors of various types and prognoses demonstrate known epigenetic markers.
Localization and growth of the metastatic tumor cells in distant location is another important event in tumor metastasis. For the tumor cells to take hold and form a new tumor at a secondary location, the more motile mesenchymal cells need to convert to an epithelial state to enable them to attach to the distant organ (MET). The reversible epigenetic changes can now turn on the reverse differentiation genes and turn off on the genes for rapid growth; this occurs once the cells are settled in the distance location.
Embryogenesis is a physiological process that involves growth and differentiation and is regulated primarily by epigenetic events. Opportunistic cancer cells and cancer progenitor cells use this process to their advantage to achieve metastasis. According to corresponding author and principal investigator Sibaji Sarkar, PhD, instructor of medicine at BUSM, the embryonic differentiation epigenetic mechanisms can be hijacked to produce disease conditions including cancer. “Permanent mutations and alterations in the genome certainly do play a role in cancer progression, but in order for the cancer to initiate, differentiate, metastasize and adapt to new locations in the body, reversible epigenetic processes are necessary.”
As an example, Sarkar presents two patients that have the same predisposition for cancer. “Though they may have the same genetic mutations that put them at an increased risk of developing cancer, they will not develop cancer at the exact same time, in the same way or in the same location, if they both develop cancer at all. Epigenetics can, in this case, be seen as the cancer kick-starter, turning on or off the genes necessary for a precancerous cell to become cancer progenitor cell,” he said.
Future studies will determine how epigenetic changes perform this “gene turn on and gene turn off” process to both initiate cancer from cancer progenitor cells and also enable them to differentiate into metastatic tumors. Understanding, and targeting, the ways in which epigenetic changes contribute to cancer progenitor cells undergoing differentiation will be crucial in developing anti-cancer drugs, anti-metastatic drugs and preventing cancer relapse.
Sarah Heerboth, a student of Boston University (BU) is the first author of this article. Other BU student co-authors are Genevieve Housman (currently a graduate student at Arizona State University), Meghan Leary, Mckenna Longacre (currently a student at Harvard Medical School), Shannon Byler, Karolina Lapinska and Amber Willbanks.
University-wide Graduate Neuroscience Program Receives BU CEIT Interdisciplinary Course Development Grant
The BU Center for Excellence and Innovation in Teaching (CEIT) has awarded the Graduate Program for Neuroscience (GPN), led by Shelley J. Russek, PhD, Professor, Pharmacology & Experimental Therapeutics and Biology, a Provost CEIT Interdisciplinary Course Development Grant. As a result of this grant, the GPN will create a curriculum spanning cutting-edge developments in systems neuroscience that link basic science to future clinical application. This unique graduate curriculum will complement the BU initiative in Systems Neuroscience and will engage contributions from the community-at-large where teaching efforts are matched with outstanding BU researchers on both the Charles River and the Medical Campuses conducting work that uses both animal models and human subjects.
Expertise in cancer treatment, PTSD, antibiotic resistance, blood transfusion
Their research runs the gamut from high-tech cancer-spotting to preventing domestic violence among veterans with post-traumatic stress disorder. And their expertise has earned them promotion to full professor on the faculty at BU’s School of Medicine. They are Gregory A. Grillone, Kalpana Gupta, Karen Quillen, and Casey Tyler Taft.
“We want to congratulate our very accomplished recently promoted professors,” says Karen Antman, dean of MED and Medical Campus provost. “These senior leaders are nationally and internationally recognized experts in their disciplines.”
Gregory A. Grillone, MED professor of otolaryngology
Grillone, vice chairman of the otolaryngology, head and neck surgery department, specializes in using spectroscopy for detection and treatment of cancer in the oral cavity and larynx. He has earned international recognition for his work on head and neck cancer screening and early detection in smokers and former smokers, and is involved in two NIH-funded studies, one as principal investigator and one as co–principal investigator. He is program director for the otolaryngology residency program and president of the American Bronchoesophagological Association. His peers have voted him one of the Best Doctors in America as well as one of America’s Best Doctors.
Foremost among Grillone’s several current research initiatives is one using spectroscopy to detect cancer in the oral cavity and larynx. “Spectroscopy is just a fancy way of saying, using light and how it absorbs and reflects off of tissues to be able to tell something about the tissue,” he says. He uses light to identify “satellite lesions under the surface…tissue that looks normal to the naked eye, but in fact is abnormal,” allowing doctors to adjust the margins of their work to be sure they remove all the cancer.
The project is a team effort with Irving Bigio, a College of Engineering professor of biomedical engineering and of electrical and computer engineering, and his Biomedical Optics Lab and others.
Kalpana Gupta, MED professor of medicine
Gupta is an expert on antibiotic resistance and its role in hospital-acquired infections, such as MRSA (Methicillin-resistant Staphylococcus aureus). She is chief of the Section of Infectious Diseases at VA Boston Healthcare System, West Roxbury campus, overseeing its HIV practice and its clinical infectious diseases, antibiotic stewardship, and infection prevention programs. She has served as chair of the International Clinical Practice Guideline for Treatment of Urinary Tract Infections in Women, which took more than four years to put together.
The project, she says, “was people sharing ideas and expert opinion, and also looking at the literature and analyzing it and interpreting it, and figuring out how to put it into a form that clinicians could use as a guide for treating UTI.” Gupta says completing the guideline was only a starting point for the long process of disseminating it nationally and internationally; the guideline will be updated in the next couple of years.
Karen Quillen, MED professor of pathology and laboratory medicine
Quillen is medical director of both the Blood Bank and the blood stem cell processing lab at Boston Medical Center. “That’s a big part of my job because the area is so heavily regulated,” she says. “Some of the clinical research projects get done on the side; I write manuscripts at night or on weekends. I imagine this is not unique to me.”
Her research focuses on improving transfusion safety for people who need repeated transfusions, notably sickle cell anemia patients. She collaborates with the University’s Center of Excellence in Sickle Cell Disease to determine why some patients become sensitized to donor red cells and other patients don’t. She has published extensively and has served on numerous national and international advisory panels, including the US Department of Health and Human Services Advisory Committee on Blood and Tissue Safety and Availability.
Last fall, Quillen cotaught an undergraduate seminar in the Kilachand Honors College based on Blood: An Epic History of Medicine and Commerce,” by Douglas Starr (COM’83), a College of Communication journalism professor. “It was my first venture into undergraduate teaching,” she says, “and it was a lot of fun.”
As a full professor, Quillen says, “I’ll continue doing what I do currently; I’m not going to change my clinical or research focus. But I might be more adventurous and explore other areas that BU is trying to emphasize, such as global health. Transfusion and treatment of blood diseases in developing countries is less advanced, and one of these days I might want to do some international work.”
Casey Tyler Taft, MED professor of psychiatry
Taft specializes in the investigation of violence in domestic relationships, with emphasis on post-traumatic stress disorder (PTSD) as both a risk factor for perpetration and as a consequence of victimization. He was the primary architect of the Strength at Home program, developed with colleagues to prevent and reduce domestic violence in military families. The program has just completed two large-scale clinical trials involving more than 500 people, veterans and their intimate partners, with promising results.
“Most men we see have some form of trauma,” often combat-related, says Taft, whose work is based at the VA Boston Healthcare System’s Jamaica Plain campus. “It’s group therapy, basically, trauma-focused.” The idea is to help veterans “manage their anger better, help them manage the situation better, and interpret other people’s intentions in a more positive light.” He and his partners are hoping to roll out the program at nine VA centers nationwide.
A staff member at the VA National Center for PTSD, Taft is principal investigator on active grants from the Department of Veterans Affairs, the Centers for Disease Control and Prevention, and the Department of Defense.
This BU Today story was written by Joel Brown. He can be reached at firstname.lastname@example.org.
White House Drug Control Policy Director Michael Botticelli has awarded Boston University School of Medicine’s Safe and Competent Opioid Prescribing Education (SCOPE of Pain) program a 2014 National High Intensity Drug Trafficking Area (HIDTA) award for Outstanding Prevention Effort.
SCOPE of Pain was launched in 2013. It is a continuing medical/nursing education training on safe opioid prescribing for chronic pain. In less than two years, the program has successfully educated more than 10,500 clinicians through online and live trainings convened throughout the country in collaboration with federal, state, and local partners, including the New England HIDTA
Chronic pain affects approximately 100 million in the U.S., making it one of the most common reasons for patients to seek medical care. Unfortunately, pain management, including the appropriate use of opioids, is not well covered in medical training. Moreover, there are inadequate numbers of pain management specialists to help generalist clinicians manage these patients.
“Clinicians who prescribe opioid analgesics to treat chronic pain are in a key position to balance the benefits and risks of chronic opioid therapy. However, they struggle with the goal of adequately managing their patients’ chronic pain while confronting the risks associated with prescription opioid misuse and abuse. We are honored that SCOPE of Pain has been recognized to address this pressing need,” said Daniel Alford, MD, MPH, dean of the office of Continuing Medical Education and associate professor of medicine at BUSM, who is the director of SCOPE of Pain.
Created by Congress in 1988, the HIDTA program serves as a catalyst for coordination among Federal, state, local, and tribal law enforcement agencies operating in areas determined to be critical drug trafficking regions of the United States. Law enforcement organizations working within HIDTAs assess drug-trafficking issues and design specific initiatives to decrease the production, transportation, distribution, and chronic use of drugs and money laundering. There are currently 28 HIDTAs located in 48 states, as well as in Puerto Rico, the U.S. Virgin Islands, and the District of Columbia.
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.
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 email@example.com.
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 firstname.lastname@example.org.
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