BUSM Faculty and Framingham Heart Study Researchers Among Thompson Reuters’ World’s Most Influential Scientific Minds 2014
BUSM faculty members and Framingham Heart Study Researchers are listed in Thompson...
On Monday, Aug. 4, members of the BUSM Class of 2018 received their white coats on Talbot Green. View the pics on Facebook.
Researchers at Boston University School of Medicine (BUSM) have uncovered important clues about a biochemical pathway in the brain that may one day expand treatment options for cognitive deficits seen in schizophrenia. The study, published online in the journal Molecular Pharmacology, was led by faculty members David H. Farb, PhD, Terrell T. Gibbs, PhD, and Shelley J. Russek, PhD in the department of pharmacology & experimental therapeutics at BUSM.
Patients with schizophrenia suffer from a life-long condition that can produce cognitive deficits, delusions, disordered thinking, and breaks with reality. A number of treatments are available for the treatment of schizophrenia, but many patients do not respond to these therapies or experience side effects that limit their use. There is no current treatment for the cognitive deficits experienced in schizophrenia.
The healthy brain is made up of billions of cells including the primary signaling cells called neurons, that are responsible for managing everything the body does: including movement, eating behavior, and memory formation. These neurons acts like a miniature computer and are controlled by substances called neurotransmitters that, like bits in a computer chip, may be “turned on” or “turned off” depending on the specific signals being integrated. Neurotransmitters latch onto a cell via a specific receptor, like a key fits into a lock.
In schizophrenia, it is thought that certain neurons don’t “turn on” as well when exposed to a certain neurotransmitter, the amino acid glutamate, may not be sensed by one of its key receptors (the NMDA receptor) whose diminished function may be the possible culprit for these sluggish cells. It is thought that this deficit can at least partially be responsible for symptoms seen in schizophrenics.
Currently the therapeutic means for making these cells more “sensitive” to glutamate can be toxic to the brain.
In this study, researchers discovered that another, naturally occurring steroid within the brain, known as PregS, may be able to bypass this toxic effect, and “turn on” neuron communication safely through a novel mechanism. The implication is that a deficit in the amount of this novel steroid may underlie deficits in signaling and that stimulation using therapeutics that elevate its levels in the brain may decrease or eradicate some of the debilitating symptoms seen in schizophrenia.
Although still in the early stages, further research in this area may be instrumental in the identification and development of treatments not only for schizophrenia, but also for other neurological conditions, such as age-related decreases in memory and learning ability.
Jasmine Chobanian, who was regarded as the “First Lady” of Boston University during the many years that her husband Aram V. Chobanian, MD, served in University leadership, both as dean of the School of Medicine and the ninth president of Boston University (2003–2005), died last Friday after a brief illness.
“Jasmine was our beloved first lady of the Medical Campus,” says Karen Antman, provost of the Medical Campus and dean of the School of Medicine. “She was a smart, savvy, warm person who started out life in the technical sciences but clearly also was deeply committed to the arts. We on the Medical Campus will miss her.”
Jasmine Chobanian was a much-loved patron of the arts and a humanitarian. She served on the board of trustees of Boston Ballet and was active in efforts to provide aid to the people of Armenia. In November 2005 the University’s Women’s Council announced the establishment of the Jasmine Chobanian Scholarship Fund and sponsored a gala honoring Chobanian for her many contributions to the University. Boston Ballet dancers Melanie Atkins, Pavel Gurevich, Roman Rykine, and Larissa Ponomarkenko performed selections from The Nutcracker, and then-provost David Campbell sang four lieder, accompanied by his wife, pianist Claude Hobson.
“Jasmine was a vivacious and caring emissary for Boston University, as she supported Aram in his roles as longtime dean of the School of Medicine and then president of Boston University,” says President Robert A. Brown. “The University has lost a true friend.”
A graduate of Brown University, Chobanian was a talented painter, and studied with Conger Metcalf at the Boston Museum School, now the School of the Museum of Fine Arts, Boston. She worked for many years as a researcher at Thorndike Memorial Laboratories at Boston City Hospital. Chobanian is being remembered by friends as someone who lived life to the fullest: a world traveler, voracious reader, fascinating raconteur, nature lover, bird watcher, and sports fan.
Caroline Apovian, professor of medicine and pediatrics at the School of Medicine, says Chobanian “was at the center of the movement on the Medical Campus to unite the arts and the sciences. She encouraged many of the faculty and students to pursue their creativity, specifically in music, but also in the other arts as well. She will be deeply missed by many.”
Robert Witzburg, associate dean and director of admissions at the School of Medicine says Jasmine Chobanian was a remarkably warm and caring person. “She had her own presence at BUSM and the University, quite independent of her prominent husband, Aram,” says Witzburg. “Her smile would light up a room, and she had that rarest of attributes: the ability to respect everyone she met and to instantly put them at ease. All of us who were privileged to know Jasmine will miss her dearly.”
Jasmine Chobanian was born in Pawtucket, R.I., the daughter of the late Charles and Zabel (Russian) Goorigian. She is survived by her husband of 59 years, Aram V. Chobanian (Hon’06), president emeritus of BU, and their children, Karin Chobanian Torrice of Natick, Mass., Lisa Chobanian Ramboeck of Bronxville, N.Y., and Aram Chobanian, Jr. of Brookline, Mass. She is also survived by her grandchildren, Marc and Vanessa Torrice; her sisters Nectar Lennox of Cumberland, R.I., and Marie Vartanian of Agawam, Mass.; and her sister-in-law, Ruth Chobanian of Cambridge, Mass., as well as a large number of nieces, nephews, and friends.
Funeral arrangements are being made through the Bedrosian Funeral Home, 558 Mt. Auburn Street, Watertown, Mass. A wake will be held at St. Stephen’s Armenian Church, 38 Elton Avenue, Watertown, Mass., tomorrow, Tuesday, July 29, from 4 p.m. to 8 p.m. Funeral services will take place on Wednesday, July 30, at 11 a.m. at St. Stephen’s Armenian Church. Burial services will be private.
In lieu of flowers, contributions may be made to the Chobanian Scholarship Fund at Boston University School of Medicine, c/o Development Office, 72 East Concord St., L219, Boston, MA 02118; St. Stephen’s Armenian Church; or The Fund for Armenian Relief, 630 Second Ave., New York, NY 10016. A memorial service to celebrate her life will be held in September at a date and place to be announced.
This BU Today story was written by Art Jahnke.
BUSM’s Domenic A. Ciraulo, MD, was appointed as the chairman of the National Institute of Alcohol Abuse and Alcoholism (NIAAA) study section AA-3, which reviews all grant applications requesting funding for clinical studies of treatments for alcoholism and health services research on alcoholism. He has been funded by NIAAA for more than 18 years, serving as a Principal Investigator at the BUSM site for the COMBINE study, PI on his own R01 grants, and mentor for a number of K awards.
Ciraulo is the chairman of the department of psychiatry at BUSM and chief of psychiatry at Boston Medical Center. He is internationally recognized as an expert in medication development and clinical trial methodology in alcoholism and addiction therapies. His research in alcoholism and addiction focuses on medication development, the interaction of psychosocial therapy and medication therapy, neuroimaging, and clinical psychopharmacology.
He has served on several national committees, including FDA advisory panels, NIH scientific review groups, and the American Psychiatry Association’s Council on Addiction Psychiatry. He is Associate Editor of the Journal of Clinical Psychopharmacology and serves on the editorial board of the American Journal of Drug and Alcohol Abuse. Ciraulo has authored or co-authored more than one hundred fifty papers and book chapters and co-edited five books. He graduated from Georgetown University School of Medicine in 1975, was a psychiatric resident at the Institute of Living from 1975-77, and Chief Resident of the Somatic Therapies Unit, Clinical Fellow Harvard Medical School, Massachusetts Mental Health Center from 1977-78.
Researchers from Boston University School of Medicine (BUSM) report variants in a new gene, PLXNA4, which may increase the risk of developing Alzheimer’s disease (AD). The discovery of this novel genetic association may lead to new drug treatment options that target PLXNA4 specifically. These findings appear in the Annals of Neurology.
AD is the most frequent age-related dementia affecting 5.4 million Americans including 13 percent of people age 65 and older, and more than 40 percent of people age 85 and older. Genetic factors account for much of the risk for developing AD with heritability estimates between 60 percent and 80 percent. However much of the genetic basis for the disease is unexplained. Less than 50 percent of the genetic contribution to AD is supported by known common genetic variations.
Using data from the Framingham Heart Study, the researchers obtained strong evidence of an association with several single nucleotide polymorphism in PLXNA4, a gene which had not been previously linked to AD. They then confirmed this finding in a larger dataset from the Alzheimer’s Disease Genetics Consortium and other datasets. Next, they performed a series of experiments in models that pinpointed the mechanism by which this gene affects AD risk. “Importantly, this is one of few single studies which go from gene finding to mechanism,” explained corresponding author Lindsay Farrer, PhD, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, epidemiology and biostatistics at BUSM.
According to the researchers a form of the protein encoded by this gene promotes formation of neurofibrillary tangles consisting of decomposed tau protein, one of the two pathological hallmarks of the disease. “We showed that PLXNA4 affects the processing of tau as it relates to neurofibrillary tangles, the primary marker of AD. Most drugs that have been developed or that are in development for treating AD are intended to reduce the toxic form of beta-amyloid, a sticky substance that accumulates in the brain of persons with AD, and none have been very effective. Only a few drugs have targeted the tau pathway,” added Farrer.
This study was supported by grants from the National Institute on Aging (R01-AG025259, P30-AG13846, R01-AG0001, U24-AG021886, U24-AG26395, R01-AG041797 and P50-AG005138), the Alzheimer Association, the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (#A110742), and the Evans Center for Interdisciplinary Biomedical Research (ECIBR) ARC on “Protein Trafficking and Neurodegenerative Disease” at Boston University.
To view the complete findings of the study, PLXNA4 is Associated with Alzheimer Disease and Modulates Tau Phosphorylation.
How can engaged patients improve health care?
BUSM’s Suzanne Mitchell, MD, and other expert panelists tackled the question during a recent TEDMED#GreatChallenges discussion, “Examining the Case for Patient Activation Measures.”
Research indicates clinical sites using the Patient Activation Measure (PAM) — a tool developed by researchers at the University of Oregon to measure patients’ knowledge, skills and confidence for managing their health — save between $260 and $3,700 per patient annually. The benefits of patient engagement extend far beyond the scope of revenue reports by promoting better communication between patients and providers.
“We’re trying to figure out how to personalize people’s care, because one size doesn’t fit all,” said Dr. Mitchell, bringing valuable insight from the clinical perspective to the discussion. “I think we can see the PAM used as a way of personalizing care, as a way of informing patients where they’re at and what they need. It could also be used as an assessment of whether a particular intervention has worked successfully to increase a person’s level of or their ability to engage in managing their own health care.”
Sustainable patient engagement is increasingly important to health care providers and administrators. To read more about the current discussion, visit George Washington University’s School of Public Health blog.
A new study shows that stress may play a role in the development of obesity.
Using experimental models, researchers at Boston University School of Medicine (BUSM) showed that adenosine, a metabolite released when the body is under stress or during an inflammatory response, stops the process of adipogenesis, when adipose (fat) stem cells differentiate into adult fat cells.
Previous studies have indicated adipogenesis plays a central role in maintaining healthy fat homeostasis by properly storing fat within cells so that it does not accumulate at high levels in the bloodstream. The current findings indicate that the body’s response to stress, potentially stopping the production of fat cell development, might be doing more harm than good under conditions of obesity and/or high levels of circulating blood fat.
The process is halted due to a newly identified signaling from an adenosine receptor, the A2b adenosine receptor (A2bAR) to a stem cell factor, known as KLF4, which regulates stem cell maintenance. When A2bAR is expressed, KLF4 level is augmented, leading to inhibition of differentiation of fat stem cells. The correlation between these two factors leads to an interruption of fat cell development, which could result in issues with fat storage within the cells and it getting into the bloodstream.
While the majority of the study was carried out in experimental models, the group also showed that A2bAR activation inhibits adipogenesis in a human primary preadipocyte culture system. Finally, analysis of adipose tissue of obese subjects showed a strong association between A2bAR and KLF4 expression in both subcutaneous (under the skin) and visceral (internal organ) human fat.
“It may seem counterintuitive, but our body needs fat tissue in order to function properly, and certain biochemical cellular processes are necessary for this to happen,” said Katya Ravid, DSc/PhD, professor of medicine and biochemistry at BUSM and director of the Evans Center for Interdisciplinary Biomedical Research who led the study. “Our study indicates that a dysfunction resulting from stress or inflammation can disrupt the process of fat tissue development, which could have a negative impact on processes dependent on proper fat cell homeostasis.”
This study is part of ongoing research interest and investigations by researchers in Ravid’s lab examining the differentiation of bone marrow and tissue stem cells and the role of adenosine receptors in this process.
Published in the Journal of Biological Chemistry, this study was done in collaboration with Noyan Gokce, MD, associate professor of medicine at BUSM and physician at Boston Medical Center; and Anna Eisenstein, graduate student of Ravid. This research was funded in part by grants awarded to Ravid by the National Heart, Lung and Blood Institute under grant award number HL93149 and the Boston Nutrition Obesity Research Center under grant award number DK046200. Gocke’s research is supported by the NIH under grant award number R01HL114675-02. Ravid also is an established Investigator with the American Heart Association.
BUSM researchers have released a guide to help primary care doctors navigate the new May 2014 American Heart Association/American Stroke Association guidelines on transient ischemic attacks (TIA).
TIA’s, commonly known as “mini-strokes” can be the first and only warning sign of a larger, debilitating stroke to come. The most common symptoms are temporary weakness on one side or speech disturbance. These ostensibly minor symptoms often prompt patients to see their primary care doctor instead of presenting to an emergency room or neurology clinic. This expert commentary, authored by Shuhan Zhu, MD, fourth year neurology resident, and Michael Perloff, MD, PhD, assistant professor of neurology at BUSM, offers insight into how primary care doctors can properly and expeditiously manage this complex and serious medical condition. The summary and recommendations appear in the American Journal of Medicine
This article includes evidence-based, up-to-date information about the shift away from a time-based definition to an ischemic tissue-based approach (reversible tissue damage) in diagnosing TIA, underscoring the increasing importance of brain imaging modalities with CT or MRI in the evaluation of TIA-like symptoms. Primary care doctors are also encouraged to use validated risk calculators like the ABCD2 score to estimate the risk of stroke following a TIA.
The best management, the authors advise, is prevention. They advocate compliance with anti-platelet or anti-coagulation therapy, rigorous management of cardiac risk factors like hypertension and diabetes, as well as lifestyle modification like smoking and alcohol cessation.
Emergency Medical Service (EMS) responders felt better prepared to respond to an active shooter incident after receiving focused tactical training according to a new study in the journal Prehospital and Disaster Medicine. This is the first study to specifically examine the EMS provider comfort level with respect to entering a scene where a shooter has not yet been neutralized or working with law enforcement personnel during that response.
Incidents such as the Columbine High School shooting, the Virginia Tech campus shooting, the 2009 Fort Hood shooting, the movie theater shooting in Aurora, Colorado, and more recently, the Sandy Hook elementary school shooting remind us of the relative frequency of these events compared to most other mass casualty incidents for which EMS trains and prepares.
For this study, EMS providers responded to an anonymous survey both before and after a four-hour training session on joint EMS/police active shooter rescue team response. Survey questions focused on individual provider comfort level when responding to active shooter incidents compared to conventional HAZMAT incidents; comfort with providing medical care in an active shooter environment; perception of EMS provider role in an active shooter incident; and the appropriate timing of EMS response at the scene.
The survey results showed that more participants felt adequately trained to respond to an active shooter incident after focused training (87 percent) compared to before the training (36 percent) regardless of a providers prior tactical experience. Additionally, more EMS providers felt more comfortable working jointly on rescue operations with law enforcement personnel in response to an active shooter incident after training participation (93 percent) compared to before the training (61 percent).
According to the researchers, despite rapid deployment of law enforcement to neutralize an active shooter, it is not uncommon for a significant amount of time to pass before law enforcement has rendered the scene “safe.” “Unfortunately this unintentionally prolongs the time before victims can receive life-saving care on the scene, as well as at a definitive care facility,” explained lead author Jerrilyn Jones, MD, a clinical instructor of emergency medicine at Boston University School of Medicine and EMS Fellow at Boston EMS. “Our study showed that after receiving appropriate training, EMS providers felt better equipped to work on joint rescue operations even if an active shooter was still present,” added Jones, who also is an emergency room physician at Boston Medical Center.
The researchers recommend further studies be undertaken to determine the significance of such training as well as the mortality impact on patient outcomes.
The American Society for Bone and Mineral Research awarded Michael F. Holick, PhD, MD, of Boston University School of Medicine (BUSM), with the 2014 Louis V. Avioli Award. Holick, a professor of medicine, physiology and biophysics at BUSM, is internationally known for revolutionizing the understanding of vitamin D and its role in disease prevention.
The award honors a member of the American Society for Bone and Mineral Research (ASBMR) for fundamental contributions to bone and mineral basic research. It is named for ASBMR’s first president and founding member, Louis Avioli, MD, who was one of the world’s leading medical authorities on osteoporosis and calcium metabolism. Holick will be recognized at the ASBMR Annual Meeting in September by the society’s president, Roberto Civitelli, MD.
“I am honored to receive this award named for my very close friend and trusted colleague,” said Holick. “I collaborated with Louis on multiple occasions, and he provided samples of blood from his patients that I used to identify, for the first time, 25-hydroxyvitamin D3 in human blood. This discovery led me to receiving a masters’ degree in biochemistry.”
Holick has revolutionized the field of vitamin D research with the identification of 1,25-dihydroxyvitamin D3, for which he received his PhD degree, which led to therapies for metabolic bone diseases, hypocalcemic disorders and psoriasis. His work raised awareness of the vitamin D deficiency epidemic and its role in causing metabolic bone disease and osteoporosis and increasing the risk of autoimmune diseases, type 2 diabetes, infectious diseases, heart disease and common deadly cancers. He has helped develop guidelines for the prevention and treatment of vitamin D deficiency with vitamin D supplementation and sensible sun exposure.
The author of more than 500 publications, Holick received his doctorate in biochemistry and attended medical school at the University of Wisconsin before completing a residency in medicine at Massachusetts General Hospital.