Learn About the Impact of Digital Simulation Technology on Medical Education and Surgical Practice
Dean of the University of California, Irvine, School of Medicine Ralph Clayman,
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Researchers Identify Novel Approach To Create Red Blood Cells, Platelets In Vitro
Finding could reduce need for blood donations, speed up research on therapies to treat diseases
Red Blood Cells and Platelets. Image courtesy of S. Kaulitzki.
A study led by Boston University School of Medicine has identified a novel approach to create an unlimited number of human red blood cells and platelets in vitro. In collaboration with Boston University School of Public Health (BUSPH) and Boston Medical Center (BMC), the researchers differentiated induced pluripotent stem (iPS) cells into these cell types, which are typically obtained through blood donations. This finding could potentially reduce the need for blood donations to treat patients requiring blood transfusions and could help researchers examine novel therapeutic targets to treat a variety of diseases, including sickle cell disease.
Published online in the journal Blood, the study was led by George J. Murphy, PhD, assistant professor of medicine at BUSM and co-director of the Center for Regenerative Medicine (CReM) at Boston University and BMC and performed in collaboration with David Sherr, PhD, a professor in environmental health at BUSM and BUSPH.
iPS cells are derived by reprogramming adult cells into a primitive stem cell state that are capable of differentiating into different types of cells. iPS cells can be generated from mature somatic cells, such as skin or blood cells, allowing for the development of patient-specific cells and tissues that should not elicit inappropriate immune responses, making them a powerful tool for biological research and a resource for regenerative medicine.
In this study, the iPS cells were obtained from the CReM iPS Cell Bank. The cells were exposed to growth factors in order to coax them to differentiate into red blood cells and platelets using a patented technology. These stem cells were examined in depth to study how blood cells form in order to further the understanding of how this process is regulated in the body.
In their new approach, the team added compounds that modulate the aryl hydrocarbon receptor (AhR) pathway. Previous research has shown this pathway to be involved in the promotion of cancer cell development via its interactions with environmental toxins. In this study, however, the team noted an exponential increase in the production of functional red blood cells and platelets in a short period of time, suggesting that AhR plays an important role in normal blood cell development.
“This finding has enabled us to overcome a major hurdle in terms of being able to produce enough of these cells to have a potential therapeutic impact both in the lab and, down the line, in patients,” said Murphy. “Additionally, our work suggests that AhR has a very important biological function in how blood cells form in the body.”
Blood transfusion is an indispensable cell therapy and the safety and adequacy of the blood supply is an international concern. In 2009, the National Blood Data Resource Center reported that blood-banking institutions collected more than 17 million units of whole blood and red blood cells and US hospitals were transfusing more than 15 million patients annually. Given the variety of blood types, there are – even in developed countries – chronic shortages of blood for some groups of patients. Sporadic shortages of blood also can occur in association with natural or man-made disasters. The number of blood transfusions is expected to increase in people over the age of 60 and could lead to an insufficient blood supply by 2050.
“Patient-specific red blood cells and platelets derived from iPS cells, which would solve problems related to immunogenicity and contamination, could potentially be used therapeutically and decrease the anticipated shortage and the need for blood donations,” added Murphy.
iPS-derived cells have great potential to lead to a variety of novel treatments for diseases given that they can be used to construct disease models in a lab. The iPS-derived red blood cells could be used by researchers examining malaria and sickle cell anemia while the iPS-derived platelets could be used to explore cardiovascular disease and treatments for blood clotting disorders.
Funding for this study was provided in part by the National Institutes of Health’s (NIH) National Heart, Lung, and Blood Institute (NHLBI) under grant award number U01 HL107443-01; a Scholar Award from the American Society of Hematology; an Affinity Research Collaborative award from the Evans Center for Interdisciplinary Research at BU; a training grant from the NIH’s NLHBI under award number 5T32HL007501-30; the NIH’s National Institute of Environmental Health Sciences under grant award numbers P01-ES11624 and P42ES007381; and the Art beCAUSE Breast Cancer Foundation.
To view an abstract of the study, visit http://bloodjournal.hematologylibrary.org/content/early/2013/05/29/blood-2012-11-466722.abstract.
“Relationship Is Everything” MED Grads Told
Doctors urged to use “privilege and power” in best possible way
Jessie Gaeta, medical director of the Boston Health Care for the Homeless Program’s Barbara McInnis House, addressed graduates at the School of Medicine’s Convocation Saturday morning. Photo by Frank Curran
A doctor’s relationship with a patient is the basis of all healing, physician Jessie Gaeta reminded a sea of newly minted doctors at the School of Medicine Convocation, held at Agganis Arena Saturday morning.
Currently medical director of the Boston Health Care for the Homeless Program’s Barbara McInnis House, Gaeta has spent her career working with patients who live in poverty, and as a result, are often chronically ill. She told the MED graduates that they are likely to work with patients with similar issues throughout their careers and urged them to passionately connect with them to build lasting relationships.
Doctors must first recognize the “structural inequities” that influence health, so they can diagnose appropriately, said Gaeta. “Then, ask yourself, how can I, with privilege and power, impact those underlying factors?…Never lose sight of the fact that what you are doing in the lab translates directly to a suffering person—let that guide you in the design and implementation of your research.”
Gaeta, currently a BU Advocacy Training Program core faculty member, was recently named a MED assistant professor of medicine. She earned a medical degree from the University of Maryland School of Medicine, and completed her internship and residency in internal medicine at Boston Medical Center, where she was appointed chief resident of internal medicine in 2001. She became a physician advocacy fellow at Columbia University’s Institute on Medicine as a Profession in 2005. There, she cofounded Home & Healthy for Good, a Massachusetts-based advocacy program that finds permanent housing for the chronically homeless and then treats their illnesses. In 2009, Gaeta was named medical director of the Barbara McInnis House, a 104-bed medical facility that provides respite care to homeless people who are too ill to stay in shelters, but not sick enough to remain hospitalized. She won the Quincy Interfaith Sheltering Coalition’s 2004 Community Hero award and was named BU Medical Center’s department of medicine Teacher of the Year in 2009.
“I am still in awe of the privilege and power we doctors are afforded, even though many years have passed since I sat where you are sitting today,” Gaeta told members of the Class of 2013. “And knowing you as I do, I know you’ll use that privilege and power in the best possible way.”
She cited her own work over the years with a homeless patient she pseudonymously called “Lisa” as an example of a doctor’s privilege in providing care to the homeless. She first met Lisa in a Boston homeless shelter and soon became her primary care physician, often helping her deal with her emphysema. But Lisa also faced extreme poverty, had no family, and was constantly anxious.
As the two women developed a trusting relationship, Gaeta realized that Lisa needed the safety and stability of a home if she was going to thrive.
“Housing was always her ‘self-management goal,’ and eventually I came to see it as the most important prescription I could write for her,” Gaeta told the graduates. “I started working with the shelter administration to prioritize her for housing, making the medical case for it, recounting her hospitals stays, and attesting that she would, indeed, be safe in housing.”
With Gaeta’s help, Lisa moved to a modest double-decker in Quincy. Her emphysema went into remission, her confidence increased, and doctors were able to give her routine checkups. When Lisa was later diagnosed with cancer, the fact that she was able to recover in her home made a huge difference, Gaeta recounted, adding that today, Lisa has a community of friends and occasionally testifies before lawmakers about the resources necessary for the homeless.
Gaeta chose to recount Lisa’s story, she said, because it proved to be a turning point in her career. Lisa taught her that a trusting relationship was the foundation for all the healing that followed.
“There are times when the ‘doing’ implied in providing care will leave you wanting at the bedside—because there is no cure, or because there is a cure but it is no match for the despair of the living conditions that the patient endures, or because no medicine will ease the suffering of the patient,” she said. “Yet you still have something healing to offer your patient: the fact that you are their doctor, all of the time, and the constancy of your relationship with them gives them a connection, a validation, and support that they might not have from anyone else.”
Gaeta urged the graduates to step outside the comfort zone of their individual clinical or scientific field of interest. “Bear witness to injustices that result in poor health, and work to remove those injustices and build health equity,” she said. “This is what healers owe society. And this is what our society desperately needs at this moment in time.”
As degrees were conferred on the Class of 2013’s 222 graduates, cheers filled the arena as some of the new doctors brought their young children on stage when they received their diplomas. The three-hour ceremony concluded with the Oath of the Scientist, read by Linda Hyman, associate provost for MED’s Division of Graduate Medical Sciences, and the Oath of Hippocrates, delivered by Karen Antman, provost of the Medical Campus and dean of the School of Medicine.
Read more about Commencement here.
This BU Today story was written by Amy Laskowski.
BUSM Commencement Photos on Facebook!
The BU School of Medicine held commencement ceremonies last week for the class of 2013. Take a peek at the Facebook albums!
GMS Commencement at Metcalf Hall
On Friday, May 17, in Metcalf Hall the Division of Graduate Medical Sciences awarded 53 students Master of Science degrees in biomedical forensic sciences, forensic anthropology, genetic counseling, and health care emergency management. One hundred twenty students received Master of Arts degrees in anatomy and neurobiology, bioimaging, clinical investigation, medical anthropology and cross-cultural practice, mental health counseling and behavioral medicine nutrition and metabolism, pathology laboratory medicine, medical sciences and clinical investigation, medical sciences and public health medical sciences oral health track, and medical sciences. View the Facebook album.
BUSM Commencement at Agannis
On Saturday, May 18, at Agganis arena, a total of 222 degrees were awarded. One hundred thirty-two students received Doctor of Medicine degrees. In addition, dual degrees in Doctor of Medicine-Doctor of Philosophy were awarded to 10 students, Doctor of Medicine-Master of Public Health to seven students, and Doctor of Medicine-Master of Business Administration to two students. Forty-five students received doctor of philosophy degrees. Check the Facebook album for more photos.
New BUSM Study Explores Providers’ Perceptions of Parental Concerns about HPV Vaccination
Human Papillomavirus (HPV) Vaccine
A new Boston University School of Medicine (BUSM) study has found that low-income and minority parents may be more receptive to vaccinating their daughters against Human Papillomavirus (HPV), while white, middle-class parents are more likely to defer the vaccination. The findings appear online in the May issue of the Journal of Health Care for the Poor and Underserved.
Cervical cancer incidence and mortality are markedly higher for low-income and minority women due to higher rates of HPV and limited access to screening and treatment. Vaccination for HPV has the potential to reduce health care disparities in cervical cancer rates if girls are vaccinated prior to sexual experimentation. Although providers felt that parents wanted to prevent cervical cancer in their daughters, some had concerns about safety of the vaccine and promoting early or unsafe sexual activity.
“Approximately 33,000 Americans will get an HPV-related cancer each year, many of which can be prevented by vaccination,” said the lead author Rebecca Perkins, MD, professor of obstetrics and gynecology at BUSM. “Solid communication between parents and providers is the key to improving HPV vaccination rates, which is what this study seeks to measure.”
Researchers interviewed 34 pediatric and family medicine physicians and nurse practitioners in four community health centers serving Boston’s low-income, minority populations. The providers answered open-ended interview questions about how they thought parents felt about vaccinating their daughters against HPV. They also were asked to role-play their HPV vaccination script using language they typically use to introduce the HPV vaccine to parents.
Immigrants, especially those from Latin America, viewed the vaccination more positively because they had experience with vaccine-preventable diseases and cervical cancer in their home countries. While providers did not note any difference in the sexual behaviors of adolescents from families of different ethnic backgrounds or incomes, they found that immigrant parents had more realistic impressions of their daughters’ sexual activity than White middle-class parents.
The findings of this study may be applicable to larger disparities seen nationwide in HPV vaccination rates. Funding for this study was provided by an American Cancer Society Mentored Research Scholar Grant MRSG- 09-151-01.
Metcalf Cup and Prize Winner: MED’s Deborah Vaughan
Her teaching formula: technology + professionalism = great doctors
Metcalf Cup and Prize winner Deborah Vaughan (GRS’72) enthusiastically road-tests new teaching technologies.
Most people return from summer vacation sporting a tan and with memories of relaxation. Deborah Vaughan came back from hers last year with hundreds of exam questions on computer software for School of Medicine students.
As passionate about work as about downtime, Vaughan (GRS’72) pioneered computer-based exams at MED and early on adopted other technology to quiz students in lectures and discussion groups. Now, conveying old-fashioned medical professionalism while seizing new-fashioned technology has won the professor of anatomy and neurobiology the 2013 Metcalf Cup and Prize, the University’s highest teaching honor.
“I was astonished” to learn of the award, says Vaughan, director of MED’s course in medical histology, the microscopic study of tissues. In addition to recognizing her innovations, she says, the award reflects “the strong support of MED for teaching, and especially the support of our talented educational technology personnel.”
For Vaughan, the human touch is every bit as important as machines are. Also MED’s assistant dean for admissions, she tries to meet personally with students, many of whom “have not previously experienced a faculty member who reaches out to them,” she says. And although she holds a PhD rather than an MD, she believes she can still “model the professionalism we attempt to develop in our students. I am available to them, I communicate readily and in a timely manner, and the respect I have for all my students is apparent to them.…I invite struggling students to meet with me, a request they appreciate and to which they respond favorably.”
Vaughan “is one of the select few who embrace change, especially when it is for the betterment of curriculum and/or for students’ learning,” according to a letter from colleagues nominating her for the Metcalf Cup and Prize. “It is more than common to receive enthusiastic emails from her before the sun rises as she beams about the latest tool she’s using to augment her course for the better.”
She has used technology to modernize histology, a course formerly involving lectures and laboratory sessions in which students examined glass microscope slides with a high-resolution light microscope. “In the late 1990s, I reversed the traditional order of a lecture followed by a laboratory session,” she says. “Thereafter, our students completed the laboratory exercises, guided by a faculty instructor,” before going to a lecture.
“This unconventional arrangement assured that the students would be familiar with the relevant histological structures and vocabulary before attending a lecture,” boosting learning efficiency, Vaughan says. In 2007, the histology course entered the digital age, losing the microscopes and slides for digitized images, leading to “a major pedagogical redesign of my course.”
Students now learn topics in three steps—self-study of tissue images; an interactive, small group discussion led by faculty; and a large lecture. “The three steps incorporate different learning approaches in different social contexts,” says Vaughan. “This design keeps the curious student engaged, while building on previously acquired knowledge.”
In 2002, she published an interactive online histology atlas as a lab guide for BU students; today, she says, it’s “an internationally popular” learning tool.
Vaughan earned a BA in biology from the University of Vermont before coming to BU for her doctorate. She did postdoctoral work in neuroanatomy here. She wrote a histology textbook and has twice won the Medical Campus Educator of the Year Award. She sits on the board of the International Association of Medical Science Educators.
The Metcalf awards, presented at Commencement, date to 1973 and are funded by a gift from the late Arthur G. B. Metcalf (SED’35, Hon.’74), a former BU professor and Board of Trustees chairman emeritus. The Metcalf Cup and Prize winner receives $10,000, the Metcalf Award winners $5,000 each. A University committee selects winners based on nominees’ statements of teaching philosophy, supporting letters from colleagues and students, and classroom observations of the teachers. John Finnerty, a College of Arts & Sciences associate professor of biology, and Carol Brennan Jenkins, a School of Education associate professor of curriculum and teaching, won this year’s Metcalf Awards.
More information about Commencement can be found on the Commencement website.
This BU Today story was written by Rich Barlow.
New NHLBI Director Speaking on BU Medical Campus, May 14
Gary H. Gibbons
Join Gary H. Gibbons, MD, the newly named director of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) during his inaugural visit to the BU Medical Campus. Dr. Gibbons will be speaking on “Setting a New Agenda for the NHLBI: Imagining Our Future” on Tuesday, May 14, 1-2 p.m. in Keefer Auditorium.
Prior to being named director of the NHLBI, which is the third largest institute of the NIH, he served as a member of the National Heart, Lung, and Blood Advisory Council (NHLBAC) from 2009-2012. He was also a member of the NHLBI Board of Extramural Experts (BEE), a working group of the NHLBAC.
Before joining the NHLBI, Dr. Gibbons served as chair of the Department of Physiology, and professor of physiology and medicine at the Morehouse School of Medicine in Atlanta. He also served as founding director of Morehouse’s Cardiovascular Research Institute, which during his tenure emerged as a center of excellence, leading the way in discoveries related to the cardiovascular health of minority populations. Dr. Gibbons received patents for innovations derived from his research in the fields of vascular biology and the pathogenesis of vascular diseases.
He earned his undergraduate degree from Princeton University, graduated magna cum laude from Harvard Medical School and completed his residency and cardiology fellowship at Brigham and Women’s Hospital in Boston. Dr. Gibbons is the recipient of numerous honors, including election to the Institute of Medicine of the National Academies of Sciences and selection as a Pew Foundation Biomedical Scholar.
Setting a New Agenda for the NHLBI: Imagining Our Future
- Gary H. Gibbons, MD, New Director National Heart, Lung, and Blood Institute (NHLBI)
- Tuesday, May 14, 1-2 p.m.
- Keefer Auditorium
Researchers Find Increased Bleeding Among Patients Taking Warfarin Who Abuse Alcohol, Drugs
Researchers at the Bedford VA and Boston University School of Medicine (BUSM) have found that substance abusers who take warfarin had more bleeding events than non-abusers. Additionally, they found that commonly obtained blood lab values might predict which patients with alcohol abuse are at a greater risk for bleeds. These findings were recently reported in the Journal of General Internal Medicine.
Drug and alcohol abuse is extremely common and some patients with substance abuse may have conditions requiring anticoagulation with blood thinning agents such as warfarin. However, the safety of prescribing warfarin among these patients is unknown. The researchers examined various labs and characteristics that might predict poor anticoagulation control and hemorrhagic events.
Among their findings:
- Patients with drug or alcohol abuse taking warfarin had poorer anticoagulation control and more major bleeds;
- Two common laboratory values of liver function, AST and ALT, specifically a ratio of theses values >1.5, predicted which patients with alcohol abuse were most likely to have poor outcomes.
Lydia Efird
“The results of this study may help doctors individualize the risks of treatment with each patient and direct future interventions,” said lead author Lydia Efird,MD, resident physician in Internal Medicine at BUSM. “Prescribing anticoagulation therapy to patients who abuse alcohol and drugs is challenging. Hopefully these findings will help clinicians stratify which of these patients may safely receive warfarin and in which patients it is best avoided,” she added.
This study was supported by the Center for Health Quality, Outcomes, and Economic Research, Bedford VA Medical Center and a grant from VA Health Services Research and Development (IIR-10-374).
BUSM Medicine Fellow Receives Annals of Internal Medicine and American College of Physicians Junior Investigator Recognition Award
Matthew Spitzer
The Annals of Internal Medicine and the American College of Physicians (ACP) recognized Matthew Spitzer, MD, BUSM Endocrine fellow in the department of Medicine with a Junior Investigator Recognition Award. He received the award in April at Internal Medicine 2013, the annual scientific meeting of the American College of Physicians, where he presented his research.
Spitzer is one of two junior physicians to receive the award, which is in its third year. Annals and ACP award the most outstanding article by a first author who is in an internal medicine residency program or a general medicine or internal medicine subspecialty fellowship program. An award also is given for the most outstanding article with a first author who is within three years of completing his or her training in internal medicine or one of its subspecialties.
Spitzer was recognized for an article he authored within three years of completing his training. “Effects of Testosterone Replacement on Response to Sildenafil Citrate in Men with Erectile Dysfunction: A Randomized Controlled Trial” was published in the November 20, 2012 issue of Annals of Internal Medicine. The research showed that men with erectile dysfunction and low testosterone levels who received a replacement dose of testosterone with sildenafil did not have greater improvement in erectile function than men who received sildenafil plus placebo.
Winners were selected based on the article’s novelty, methodological rigor, clarity of presentation, and potential to influence practice, policy, or future research. Judges include Annals’ editors and representatives from Annals’ Editorial Board and the American College of Physicians’ Education and Publication Committee.
BUSM Researchers Discover Possible Mechanism for Anxiety and Depression
Valentina Sabino
Researchers at Boston University School of Medicine (BUSM) have discovered what they believe to be a major brain mechanism responsible for a heightened state of anxiety and possibly depression. The study, published in the journal Neuropsychopharmacology, involves a protein called pituitary adenylate cyclase-activating peptide (PACAP), a hormone and molecule in the brain, and its relationship with anxiety and depression.
Anxiety disorders are a serious public health problem because they represent the most common mental disturbances in the United States and are responsible for almost one third of the total health care costs. In addition, depression often occurs together with anxiety disorder in patients.
In their study, the researchers were found to be able to induce feelings of anxiousness and depression in a preclinical model after administering PACAP. According to the researchers it was both surprising and very interesting to find that the same molecule could induce both anxious and depressive feelings.
Importantly, the scientists also found that the mechanism of the anxiety and depression-inducing effects of PACAP involves another important and well known molecule and hormone, called corticotropin-releasing factor (CRF). Indeed, when the authors provided PACAP to the model, they observed an increase in the production of CRF in two important regions of the brain, the hypothalamus and the amygdala. More importantly, when the authors introduced a substance that blocked the receptors of CRF, PACAP could no longer induce anxiety and depression.
“In humans, a dysfunction of the amygdala PACAP system may therefore be responsible for the development of conditions involving atypical responses to stressors, including generalized anxiety, PTSD and depression,” said senior study author Valentina Sabino, PhD, assistant professor of pharmacology and psychiatry in the Department of Pharmacology at BUSM as well as co-director of the Laboratory of Addictive Disorders
Also contributing to this study were Riccardo Dore, PhD; Attilio Lemolo, PhD, Karen L. Smith, PhD, Xiaofan Wang PhD and Pietro Cottone, PhD. The Laboratory of Addictive Disorders at Boston University School of Medicine is continuing this line of research to better understand the neurobiology of the PACAP system, with the hope of ultimately developing new therapeutic agents for the treatment of these debilitating psychiatric diseases.
Funding for this study was provided by the National Institute of Mental Health, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. In addition, funding was made available by the Peter Paul Career Development Professorship and by Boston University’s Undergraduate Research Opportunities Program.
May 13 Kirshenbaum Lecture: Constitutional Dimensions of the Doctor-Patient Relationship Presented by George Annas
George Annas. Photo by Vernon Doucette
George Annas, JD, MPH, recognized expert on health law, bioethics and human rights, scholar and teacher, will present the annual Howard D. Kirshenbaum, MD, Lecture to the medical campus community including members of Dr. Kirshenbaum’s family on Monday, May 13. He will speak on “Constitutional Dimensions of the Doctor-Patient Relationship”
Annas is the William Fairfield Warren Distinguished Professor, the Edward R. Utley Professor, and Chair of the Department of Health Law, Bioethics and Human Rights at BU School of Public Health and a professor in both the School of Medicine and the School of Law. He earned a JD from Harvard Law School and an MPH from Harvard School of Public Health, where he was a Joseph P. Kennedy Fellow in Medical Ethics. Annas clerked for Justice John V. Spalding of the Massachusetts Supreme Judicial Court before coming to BU in 1972 as the director of the Center for Law and Health Sciences at the Law School.
Author or editor of 16 books on health law and bioethics, Annas has been characterized as “the father of patient rights.” He is a member of the Institute of Medicine of the National Academies, a fellow of the American Association for the Advancement of Science, co-chair of the American Bar Association’s Committee on Health Rights and Bioethics, and a member of the Committee on Human Rights of the National Academies. Annas is the cofounder of Global Lawyers and Physicians, a transnational professional association of lawyers and physicians collaborating to promote human rights and health. He has also held a variety of government regulatory posts.
His presentation, “Constitutional Dimensions of the Doctor-Patient Relationship” will be given in memory of Dr. Kirshenbaum, a highly regarded cardiologist, who died May of 2010. The Kirshenbaum Lecture was established by Elaine Kirshenbaum, wife of Dr. Kirshenbaum. A graduate of BU College of Liberal Arts, BU School of Education and BUSPH, Mrs. Kirshenbaum is a member of the Boston University Board of Trustees and a member of the School of Medicine Dean’s Advisory Board. Son, Daniel, graduated from BUSM in 2011 and daughter, Jennifer, graduated from BU School of Law.
Howard D. Kirshenbaum, MD Lecture
- Constitutional Dimensions of the Doctor-Patient Relationship
- George J. Annas, JD, MPH
- Monday, May 13, 5 p.m.
- 670 Albany St., First Floor Auditorium
- Reception to follow
