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...
BUSM faculty members and Framingham Heart Study Researchers are listed in Thompson Reuters’ The World’s Most Influential Scientific Minds 2014. Reuters’ list of “some of the best and brightest scientific minds of our time” is determined by analyzing data on which researchers have produced work that is most frequently acknowledged by peers. Reuters analyzed at citation data over the last 11 years to identify those who published the highest impact work (2002-2012 and 2012-2013).
Faculty Michael Holick (medicine, physiology and biophysics) and Alice Jacobs (medicine/cardiology) are listed under clinical medicine as are BUSM/BU Framingham Heart Study researchers Emily Benjamin (medicine/cardiology), Ralph D’Agostino (mathematics/statistics), Martin Larson (mathematics/statistics), Daniel Levy (medicine/cardiology), Joseph Massaro (biostatistics), and Vasan Ramachandran (medicine/cardiology).
“Everyone acknowledged in this book is a person of influence in the sciences and social sciences. They are the people who are on the cutting edge of their fields. They are performing and publishing work that their peers recognize as vital to the advancement of their science. These researchers are, undoubtedly, among the most influential scientific minds of our time.” (Thompson Reuters’ The World’s Most Influential Scientific Minds 2014)
On August 11, third-year BUSM student Leslie Maness, one of six 2014 Margaret E. Mahoney Fellows, presented her summer research project at the New York Academy of Medicine (NYAM). The Mahoney Fellowship program of the NYAM provides stipends for outstanding medical, dental, public health, public policy and graduate nursing students to conduct summer research projects on some aspect of health care delivery transformation for vulnerable populations and/or early childhood health and development with an emphasis on policy implications.
Maness conducted her research at New York University School of Medicine/Bellevue Hospital on the impact of low health literacy and limited English proficiency on parent/caregiver medication dosing errors when delivering liquid medications to children. She also participated in workshops on leadership, conflict management and negotiation, the policymaking process, and communications and media. Mahoney Fellows met with health care leaders including Dr. Donna Shalala, former Secretary for Health and Human Services; Dr. Lilliam Barrios-Paoli, New York Deputy Mayor for Health and Human Services; Dr. Mary Bassett, New York City Health Commissioner; Dr. Pamela Riley, Assistant Vice President for Delivery System Reform at The Commonwealth Fund; and Dr. Robert Brook, Distinguished Chair in Health Care Services at the RAND Corporation.
“This is quite a unique fellowship, in that it provides graduate health professions students with an introduction to the health policy world and opportunities for engagement with health policy leaders at this formative stage in their education and career,” said NYAM President Jo Ivey Boufford, MD. “It is our hope that the Mahoney Fellows will each build this connection into their career trajectory.”
An editorial published in this week’s JAMA highlights the importance of physicians using all available clinical assessment tools when considering how to treat patients. Written by Robert Vinci, MD, chief of pediatrics at Boston Medical Center and chair of pediatrics at Boston University School of Medicine and Howard Bauchner, MD, editor-in-chief of JAMA, the editorial examines results of a study published in the same issue of the journal as an example of how doctors can often over-emphasize certain types of data.
The study examined how pediatric emergency medicine physicians treat a respiratory tract infection called bronchiolitis in infants, and how they incorporate factors such as respiratory exam, imaging tools and blood tests when deciding on treatment. Doctors also commonly use the level of oxygen saturation, measured by a simple machine called an oximeter, which measures how well the blood carries oxygen; generally, the higher the number, the better.
In the study, emergency department physicians were presented with two groups of infants with bronchiolitis, one in which they were shown the true oxygen saturation level and the other in which they were shown an altered number that was three percent higher than the actual saturation level.
The results indicated that the clinicians were 40 percent less likely to admit the patients with the falsely higher oxygen saturation level into the hospital even though the two groups had otherwise similar symptoms and illness severity. This supports the notion that clinicians may often overlook other important components of the clinical assessment in favor of a single parameter.
The editorial stresses the challenges that clinicians often face in treating disorders where there are no standard treatment protocols and emphasizes that analyzing all available data to make the best clinical judgments and decisions is the true art of medicine.
“Although it may seem wrong, the study authors followed established guidelines such as obtaining consent from parents and also ensured the safety of patients by only enrolling patients with mild disease,” said Vinci about the ethics of deceiving physicians for the purpose of research in the editorial. “In an area of research where there is much uncertainty about how we should best treat patients, studies such as this may be necessary to gather important information, as long as researchers ensure patient safety.”
Read the full editorial in JAMA.
The recipients of the CTSI pilot grants for 2014 have been announced by BU Medical Campus Provost and BU School of Medicine Dean Karen Antman, MD.
Funding for these grants come entirely from BU, BMC and the VA this year for the first time, without relying on NIH funds, an accomplishment meeting the goals of the NIH’s CTSA program.
Eleven $20,000 grants support School of Medicine faculty, including seven funded by the School of Medicine four of which come from the Wing Tat Lee (WTL) endowment to promote School of Medicine and Chinese university collaborations, three by Boston Medical Center, and one by the VA Boston Healthcare System
Three $20,000 grants were funded by BU Henry M. Goldman School of Dental Medicine and nine grants totaling more than $90,000 were funded by BU School of Public Health.
The CTSI solicits pilot grant applications annually and are reviewed by panels of BU researchers. Between 2008 and 2013 the CTSI pilot award program, in collaboration with other BU/BMC schools, departments and centers, awarded more than $1.3 million to 55 investigators for 57 projects across five schools and 23 departments/sections. These pilot grants have led to 28 additional grants from external funders totaling more than $9.4 million, greater than a seven-fold return on investment-to-date.
Probing deeper into the complex decisions that parents and providers face regarding the human papilloma virus (HPV) vaccine, researchers found that though both parties appreciated importance of the HPV vaccine, their personal assumptions surrounding timing of administration relative to onset of sexual activity resulted in decreased vaccination rates.
Researchers at Boston University School of Medicine (BUSM) conducted hundreds of interviews to offer new insights into this frequent—and often controversial—clinic room conversation. Their findings and recommendations will appear in the September 2014 issue of Pediatrics.
Specifically, researchers found that vaccination rates could be traced to personal biases and communication styles of providers. Providers who believed a child was at low risk for sexual activity—an assessment, they admitted, not always accurate—were more likely to delay administration. Often, this deferred decision was never readdressed. Those with high vaccination rates approached HPV vaccines as a routine part of the age 11 vaccine bundle, unequivocally recommended it to parents, and framed the conversation as one about cancer prevention.
“Emphasis on cancer prevention and concurrent administration with other routine childhood vaccines has the potential to dramatically reduce missed opportunities occurring among well- intentioned providers and parents,” explained lead author Rebecca Perkins, MD, MSc, assistant professor of Obstetrics and Gynecology at BUSM and a gynecologist at Boston Medical Center.
The researchers interviewed 124 parents and 37 health-care providers at four clinics between September 2012 and August 2013. Parents and providers were asked to discuss their reasons why their HPV vaccine eligible girls did or did not ultimately receive the vaccine. Remarkably, the most common parental reason (44 percent) was that their child was never offered the vaccine. Other common reasons included the perception that the vaccination was optional instead of recommended or being told by their provider that it was unnecessary prior to sexual debut. Among those that declined the vaccine, the rationale often involved safety concerns and a belief that their daughters were too young to need it.
What is HPV?
A common and deadly cancer—12,000 women are diagnosed and 4,000 will die from it annually—cervical cancer is unique in that it is the only cancer that can be prevented by a vaccine. HPV causes not only cervical, vaginal and vulvar cancers in women, but penile cancers in men, as well as cancers of the mouth, tongue, tonsils and anus in men and women. The same viral strains are responsible for most of these cancers, and are covered by currently available vaccines.
Cervical cancer arises from abnormal cells on the cervix, known as cervical dysplasia; the majority of dysplasia arises from HPV strains numbered 16 and 18. The HPV vaccine, in turn, prevents 98 percent of cases caused by strains 16 and 18. Despite this evidence, HPV vaccination rates for girls lag far behind that of other types of vaccination; only 54 percent of eligible girls will ever get one of the three required doses, whereas only 33 percent will ever complete the entire sequence. This lag in uptake stems, in large part, from unfounded concerns about vaccine safety promulgated in popular media and, because HPV is transmitted sexually, parental / provider discomfort when contemplating a child’s future sexuality. The HPV vaccine is currently recommended to be administered to girls and boys at ages 11-12, with catch-up vaccination through age 26 for girls and 21 for boys.
Funding for this study was provided by Centers for Disease Control and the American Cancer Society.
For the full findings of this study in Pediatrics: Missed Opportunities for HPV Vaccination in Adolescent Girls.
Researchers from Boston University School of Medicine (BUSM) report that a tumor suppressor pathway, called the Hippo pathway, is responsible for sensing abnormal chromosome numbers in cells and triggering cell cycle arrest, thus preventing progression into cancer.
Although the link between abnormal cells and tumor suppressor pathways—like that mediated by the well known p53 gene—has been firmly established, the critical steps in between are not well understood. According to the authors, whose work appears in Cell, this work completes at least one of the missing links.
Normal human cells contain 23 pairs of chromosomes, but this number doubles to 46 pairs as a cell prepares to divide. At the end of a normal cell division cycle, these chromosomes evenly divide to produce two identical cells with 23 pairs of chromosomes each. Sometimes, however, errors occur during division and cells fail to divide properly, resulting in giant cells with double the number of chromosomes, known as a tetraploid cells. Normally, p53 dependent pathways stop these tetraploid cells from proliferating. This response is critical because those tetraploid cells that escape detection can facilitate cancer development: Recent studies suggest that as many as 40% of all solid tumors have passed through a tetraploid stage at some point during their development. Thus, there has been great interest in understanding how a cell “knows” it has a tetraploid complement of chromosomes and is in need of tumor suppression.
Using a technique known as genome-wide screening, the scientists systematically depleted every human gene from tetraploid cells in order to discover which ones were important to prevent proliferation. They found that when one specific gene, LATS2, was eliminated, the arrested tetraploid cells resumed proliferation, thus demonstrating that LATS2 was an upstream gene responsible for halting abnormal cell division. The LATS2 gene is known to activate the Hippo tumor suppressor pathway, which is the same pathway our bodies use to ensure our vital organs don’t grow out of control. Now, the authors demonstrate that the Hippo pathway also represents the underlying pathway that prevents tetraploid cells from proliferating and causing tumors. “Although more studies are needed to further clarify this critical pathway, this work may help guide the development of new therapies that specifically target tumor cells with abnormal numbers of chromosomes, while sparing the normal healthy cells from which they originated,” explained corresponding author Neil J. Ganem, PhD, Assistant Professor of Pharmacology and Medicine in the Shamim and Ashraf Dahod Breast Cancer Research Laboratories at BUSM.
Funding for this study was provided in part by a K99/R00 from the National Cancer Institute.
In a scientific discovery that has significant implications for HIV vaccine development, collaborators at the Boston University School of Medicine (BUSM) and Duke University School of Medicine have uncovered novel properties of special HIV antibodies. The paper, published in Cell Host and Microbe, describes how some HIV antibodies experience an unusual type of mutation, a phenomenon that allows them to neutralize many different strains of HIV. These antibodies are called “broadly neutralizing antibodies,” or BNAbs.
Antibodies develop from immune cells known as B cells. When B cells are confronted with foreign elements (known as antigens), some of them experience a high rate of mutations resulting in the substitution of an amino acid within the antibody for another. B cells whose antibodies carry variations that allow them to bind tightly with antigens proliferate, whereas those that do not die off. Thus, the immune system is able to adapt constantly by utilizing its own very fast version of evolution. More rarely, the antibodies will experience more dramatic changes than single amino acid substitutions. When whole strings of amino acids are inserted or deleted, this is known as an indel. Less than four percent of human antibodies contain indels; in BNAbs this figure is more than 50 percent. Only a small subset of HIV-infected individuals produce BNAbs.
Comparing the antibody genes of HIV infected and non-infected individuals, scientists discovered that HIV infected individuals had 27 percent more insertions and 23 percent more deletions than non-infected individuals. They also found this elevated rate of mutation persisted in all HIV-infected individuals, regardless of their ability to produce BNAbs. Most importantly, this high rate of indels was due to an overall increase in mutation frequency rather than something special associated with HIV itself, or unusual characteristics of the people who are able to make BNAbs. “This result suggests that a BNAb-eliciting vaccine is possible after all,” explained lead and corresponding author Thomas B. Kepler, PhD, professor of microbiology at BUSM. “More than 80 percent of indels were found in genetic regions responsible for binding to the HIV virus,” he added.
Since the BNAb indels don’t result from special characteristics of the people who make them, the researchers suspected that the indels may be important for the antibody function. They studied one particular BNAb called CH31, which has a very large indel, to see what role these indels might have played in the acquisition of broad neutralizing activity. They found that the indel was the key event in the development of CH31. According to the researchers just putting the indel into antibodies that did not originally have it, increased its effectiveness eight-fold; taking it away from ones that did have it initially, made them much worse. “When tested on their ability to broadly neutralize HIV, only those CH31 antibodies with indels were able to accomplish the task,” said Kepler.
Barton Haynes, MD, director of the Duke Human Vaccine Institute and senior author noted, The more we understand about the unusual pathway the BNAbs take to develop, the better chance we will have in inducing them. This news study unravels a particularly complex BNAb pathway.” The great hope in the quest to prevent HIV-1 is the development of a single vaccine that can cover multiple forms of HIV-1. A vaccine that works by eliciting BNAbs is a major goal, and this new work suggest that strategies for such a vaccine should focus on speeding up the antibody evolution that occurs after every immunization. The study suggests that such a strategy could work in everyone, not just a lucky few.
Other institutions involved in this study included the National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa; the Center for AIDS Program of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa; the Vaccine Research Center, NIAID, NIH, Bethesda, MD and Stanford University Medical Center, Stanford, CA
Funding for this study was provided by the National Institutes of Allergy and Infectious Diseases.
In some women abnormally high levels of a common and pervasive chemical may lead to adverse effects in their offspring. The study, published recently in the Journal of Clinical Endocrinology & Metabolism, is the first of its kind to shed light on the possible harmful side effects of perchlorate in mothers and their children.
Using data from the Controlled Antenatal Thyroid Study (CATS) cohort, researchers at Boston University School of Medicine (BUSM) and Cardiff University studied the effect of perchlorate, an environmental contaminant found in many foods and in some drinking water supplies, and its effects on children born to mothers with above average levels of this substance in their system. They studied 487 mother-child pairs from women with underactive thyroid glands and in the 50 women with the highest levels of perchlorate in their body, their offspring had below average IQ levels when compared to other children.
“The reason people really care about perchlorate is because it is ubiquitous. It’s everywhere,” said Elizabeth Pearce, MD, MSc, associate professor of medicine at BUSM. “Prior studies have already shown perchlorate, at low levels, can be found in each and every one of us.”
Perchlorate is a compound known to affect the thyroid gland, an organ needed to help regulate hormone levels in humans. According to Pearce previous studies have attempted to implicate this anti-thyroid activity in pregnant mothers as a possible cause of hypothyroidism, or an underactive thyroid gland. Hypothyroidism in newborns and children can lead to an array of unwelcome side effects, including below average intelligence.
Funding for the original CATS study was provided by the Wellcome Trust and Compagnia de San Paulo, Turin.
Researchers from Boston University School of Medicine (BUSM) report that two rare variants in the AKAP9 gene significantly increase the risk of Alzheimer’s disease (AD) in African-Americans.
This previously unknown association furthers the understanding of the role of genetic factors in the development of AD, according to the researchers, whose findings appear in Alzheimer’s & Dementia.
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. Up to 75 percent of AD cases are thought to have a genetic basis; however the specific genes involved likely differ between ethnic populations. The most well-known AD risk gene, APOE4, does not play as strong a role in AD risk in African Americans as it does in Caucasians, despite the fact that a higher proportion of African Americans than Caucasians are afflicted with this disorder.
By analyzing the DNA sequence for all genes from participants of the Multi-Institutional Research on Alzheimer Genetic Epidemiology (MIRAGE) Study and Genetic and Environmental Risk Factors for Alzheimer’s Disease among African Americans (GenerAAtions) Study, researchers identified two genetic variants in AKAP9 unique to African Americans that are enriched in individuals with AD. They then confirmed this association in several thousand other African American subjects in the Alzheimer Disease Genetics Consortium dataset. Carriers of either of these AKAP9 variants have a respective 2.8 and 3.6 times greater risk of developing AD.
According to the researchers AKAP9 encodes a protein with multiple forms, One of these, AKAP450, is expressed in the brain and responsible for microtubule anchoring and organization. Another protein, tau, which is responsible for microtubule functioning is well known to be the key constituent of neurofibrillary tangles that accumulate in AD brains.
“While further work is needed to clarify the causal link between these AKAP9 variants and AD, “this study indicates a new potential disease mechanism in the quest for a better understanding of AD, particularly in African Americans,” explained senior author Lindsay Farrer, PhD, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, epidemiology and biostatistics at BUSM. “Moreover, this is the first authentic example of rare genetic variants conferring a high risk of AD in African Americans,” he added.
Funding for this study was provided by the National Institute on Aging (R01-AG025259, R01-AG09029, P30-AG13846, and U01-032984).
Read the full study in Alzheimer’s & Dementia.
A recently completed renovation on the 11th floor of the Alumni Medical Library now provides a state-of-the-art, 220 seat testing center. The testing center is among the first of its kind, and will serve to both facilitate the administration of exams while at the same time enhancing the quality of study space for BUMC students.
Renovations include a new ceiling with improved sound-proofing qualities, energy-efficient lighting, new carpeting and flooring, newly painted walls, new chairs and tables with power outlets at every seat, and club seating and cube tables in the hallway outside the floor-to-ceiling glass walls of the testing center. The heating and air conditioning system was upgraded, and a more powerful wireless system is provided throughout the testing center, as well as some wired network connections.
The testing center is equipped with a video monitoring system and an audio system for proctor announcements. During exams, proctors will have video monitoring controls to observe activity throughout the space via iPad. The testing center serves a dual-purpose as student study space when not reserved for exams.
Medical Library Computing & Systems offices are located on L-11, and staff will provide on-site technical support for student laptops and laptop loaners during exams. A new state-of-the-art computer classroom with 26 PCs will also serve as a public computing lab when classes and exams are not scheduled. A coffee/vending lounge includes additional club seating, group study tables, PCs, a scanner and print release station. The elevator lobby was renovated and a new LCD monitor and signage have been installed throughout the floor.