By Lisa Brown

BUMC Students to Enjoy Newly Renovated Space on 11th Floor Alumni Medical Library

August 7th, 2014 in Uncategorized

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.

Testing Center interior

Testing center interior

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.

Hall outside of Testing Center

Hall outside of testing center

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.

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Battling Ebola: How Ebola Kills

August 5th, 2014 in Uncategorized

MED’s John Connor is devising diagnostics to spot Ebola and antivirals to treat the disease

On Saturday, Aug. 2, the first of two sickened American health care workers was flown from Africa to a special containment unit at Emory University. Despite the risk of infection, medical personnel continue to travel to West Africa to help bring under control the worst Ebola outbreak on record, which has killed more than 900 people to date. The World Health Organization plans to spend $100 million to fight the outbreak, and the Centers for Disease Control and Prevention will send 50 more aid workers.

In this Special Report, BU Today talks to Boston University researchers in several fields about why medical personnel confront the risks; the ethical and political dilemmas presented by the outbreak; how the virus kills; efforts to design effective therapies; and other aspects of this unprecedented outbreak of Ebola.

John Connor, a researcher at BU’s National Emerging Infectious Diseases Laboratories (NEIDL), says the immune system’s response to Ebola is “totally out of whack” compared with its responses to other viruses. Photo by Kalman Zabarsky

John Connor, a researcher at BU’s National Emerging Infectious Diseases Laboratories (NEIDL), says the immune system’s response to Ebola is “totally out of whack” compared with its responses to other viruses. Photo by Kalman Zabarsky

The Ebola outbreak in Guinea, Sierra Leone, and Liberia has now infected more than 1,600 people, according to the World Health Organization. To learn about how the virus kills and efforts being made at BU to devise diagnostics and therapies to treat it, BU Today spoke with John Connor, associate professor of microbiology at the School of Medicine and a researcher at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL). Connor, whose research is funded by the National Institute of Allergy and Infectious Diseases, studies the tricks that viruses use to dominate their cellular hosts. He has been working collaboratively with researchers at BU and at other research institutions, with a particular focus on the Ebola virus.

BU Today: What aspect of the Ebola virus is the focus of your work?

Connor: My lab is interested in several different approaches to try to understand and stop diseases caused by viruses like Ebola. This includes the development of antivirals, vaccines, and point-of-care diagnostics, in collaboration with the Photonics Center and the lab of Selim Unlu, College of Engineering associate dean for research and graduate programs in the department of computer and electrical engineering.

Another thing we are looking at is what goes wrong with the immune response during viral infection. Our bodies are so good at responding to so many diseases, and in most cases we get sick for a couple of days and then we get better. Our response to Ebola is totally out of whack. The immune system appears to deliver a much more aggressive response than is necessary, one that causes a lot of damage to the body. That overreaction is a significant part of what makes infection with this virus so deadly.

What kind of damage is done by the overreaction?

The response is so strong that it triggers other pathologies. This can include diffuse intravascular coagulopathy, which is why the virus is often called a hemorrhagic fever virus. Normally, coagulation is constantly serving your body, so if you get cut you get a nice blood clot that seals you up. It’s a great way to keep your blood from leaking out. In the case of Ebola, you get clotting in inappropriate places, such as organs like the liver. The problem is, you have a finite number of clotting factors in your body, and they get depleted from the inappropriate clotting. When that happens, you have a hole in your body that needs clotting but won’t stop bleeding. All the small things that happen on a daily basis that are normally taken care of by coagulation are not working.

Do other viruses cause the same coagulation problems?

Ebola is one of the viruses that are most associated with that type of response. The Marburg virus, a cousin of Ebola, can also cause that response, and Lassa fever viruses can as well. Dengue virus can also cause a hemorrhagic disease, in rare cases.

Does every victim of Ebola hemorrhage?

No, but it happens a lot of the time, whereas in other viral infection such as the common flu, it does not happen.

Why is it that some people infected by Ebola get much sicker than others?

That’s one of the things we are trying to learn, but it’s hard. One of the problems of studying a virus like this is that you don’t have large pools of people to work with. Outbreaks of Ebola are sporadic. If you are studying HIV/AIDS, the prevalence of the disease means that you can readily identify 10,000 people. Ebola outbreaks are not predictable and, thankfully, most previous outbreaks were small. This makes other approaches to understanding the course of disease important to try. We are now collaborating with people at other labs who are using animal models of the disease.

What are you learning about how the virus works?

One of the things we’ve been surprised by is how early the immune system response begins and how robust it is. When we compare this response to other viruses, it appears that the response to Ebola is much stronger than to other types of disease. Also, it appears that specific types of responses are associated with survival from the disease. We are investigating whether this early immune response can be used to develop a diagnostic for early disease. Can we look very early, even before symptoms show up, and identify an immune system response to an Ebola infection?

How is the immune response of survivors different from that of people who die?

We have learned that it’s not just the intensity of the response. It also appears to be the type of responses that develop. One of the things we see in animals that succumb to the disease is one type of immune cell—a type of neutrophil—accumulates, whereas in animals that survive, that immune cell is not as abundant.

Are there any therapies that are effective?

There are no Food and Drug Administration–approved therapies. People are beginning to develop some therapies, and information from those studies says that the earlier an individual is treated, the better their survival.

If we can find ways to diagnose infection early, that will directly help effective therapy. And with early diagnosis, if you identify one patient that is symptomatic, suggesting that their course of disease is far along, early tests like the one we are developing will allow rapid testing of contacts of that first patient and early treatment of those infected with the disease.

We are really trying to understand what this very overactive immune response is and how we can start damping it down. Our lab is also developing antivirals that work against Ebola, and we are working on diagnostics that will be at the point of care. We have been focusing on developing a diagnostic for Ebola, Marburg, and Lassa, where point of care is a high priority. We are doing this with the Unlu laboratory at BU, with collaboration from BD Technologies and a spin-out company, NeXGen Arrays, which was started by BU alums and is primarily interested in developing these assays. We are also developing second-generation vaccine viruses in collaboration with Tom Geisbert, former associate director of the NEIDL. The collaboration started when Tom was at BU and has continued since his move to the University of Texas Medical Branch.

This BU Today story was written by Art Jahnke. He can be reached at jahnke@bu.edu.

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Battling Ebola: Heading Into the Outbreak

August 4th, 2014 in Uncategorized

NEIDL’s Nahid Bhadelia to care for patients, share expertise

On Saturday, Aug. 2, the first of two sickened American health care workers was flown from Africa to a special containment unit at Emory University. Despite the risk of infection, medical personnel continue to travel to West Africa to help bring under control the worst Ebola outbreak on record, which has killed more than 900 people to date. The World Health Organization plans to spend $100 million to fight the outbreak, and the Centers for Disease Control and Prevention will send 50 more aid workers.

In a weeklong Special Report, BU Today talks to Boston University researchers in several fields about why medical personnel confront the risks; the ethical and political dilemmas presented by the outbreak; how the virus kills; efforts to design effective therapies; and other aspects of this unprecedented outbreak of Ebola.

Nahid Bhadelia (right) in protective gear with Dr. Guillermo Madico, at the National Emerging Infectious Diseases Laboratory in Boston, where she directs infection control. This equipment is slated to be donated to the Ebola-fighting efforts in Sierra Leone when she travels there in mid-August. Photos by Jackie Ricciardi

Nahid Bhadelia (right) in protective gear with Dr. Guillermo Madico, at the National Emerging Infectious Diseases Laboratory in Boston, where she directs infection control. This equipment is slated to be donated to the Ebola-fighting efforts in Sierra Leone when she travels there in mid-August. Photos by Jackie Ricciardi

If all goes as planned, Dr. Nahid Bhadelia will soon head straight into the heart of the Ebola outbreak that has already killed more than 800 people in western Africa, including at least 50 health care workers. Global and US health authorities announced Thursday that they would ramp up efforts to bring the epidemic under control, but that it would likely take at least three to six months.

Bhadelia is director of infection control at Boston University’s National Emerging Infectious Diseases Laboratory, an assistant professor of infectious disease at BU School of Medicine, and an associate hospital epidemiologist at Boston Medical Center. With funding provided by the World Health Organization (WHO), she’s slated to travel to Sierra Leone in mid-August, to share her expertise on infection control and also care directly for Ebola patients. We spoke about the growing crisis.

WBUR’s CommonHealth: This is the biggest Ebola outbreak ever, as far as we know. Is it notable in other ways?

This is the first time Ebola has been present in these three countries: Sierra Leone, Guinea, and Liberia. Because these countries haven’t seen the infection before, that impacted their ability to recognize and manage the infection early on.

Also, because of the recent travel of the American Patrick Sawyer to Lagos [where he died of Ebola], I think it has raised a lot more concern about transfer of Ebola abroad, which has not been much of an issue in the past.

A lot of the US media coverage has focused on, “Could it come here?” Part of that fear seems to stem from the sense that Ebola, with its hemorrhages and high death rate, is particularly horrible. Is it?

In some ways yes and in others no. Ebola Zaire, the strain we’re seeing right now, is one of the most deadly strains; it’s been shown in the past to have 90 percent mortality when no treatment is given. But in some ways, it’s much harder to transmit at a population level compared to respiratory viruses we’ve been hearing about such as SARS or MERS. It requires close contact with bodily fluids. So, for example, there’s been a lot of concern about travel of folks from the areas impacted to the developed world, and I think the reason it’s less likely to spread is because it’s limited to people who come into contact very closely with the person who’s impacted.

So many health care workers have been getting infected. Do you have a sense of why? Are there practices that might be easily correctable that you could have an impact on?

There are a lot of talented people there in the field already, not just from international organizations but people who’ve been working there a very long time. In Sierra Leone, for example, though they haven’t had Ebola before, they’ve dealt with Lassa fever, another viral disease that causes hemorrhagic fever, at Kenema—one of the places where Dr. Sheik Umar Khan, the leading physician who just died of Ebola, worked. That center has dealt with Lassa fever for over 25 years, and there are nurses there who have long experience. The issue is the amount of patients. You have nurses there who were taking care of maybe a dozen Lassa patients and now they have to see 70 Ebola patients. I think the major issue is the fact that the health care system is so overwhelmed.

One of the major ways to alleviate that would be the presence of more personal protective equipment and more sterile medical equipment in general. I know that the PPE—the personal protective equipment—is a major concern because there’s a dearth of it right now in the field.

Also, we understand that the virus can be transmitted from surfaces—so if someone comes into contact with bodily fluids with the virus in them on a surface, that’s another way to get it. The virus can live outside the host for a couple of days. So this contamination of the environment is another important component—and that’s very difficult if you can imagine 70 patients in a small space. Ebola is not hard to kill, so it’s easy to avoid contamination in general. It’s only because of the number of people and poor health infrastructure that it becomes difficult.

14-7999-BHADELIA-( Portrait = Full Name)

Still, it’s so baffling that these leading, incredibly knowledgeable doctors are getting infected. How can that happen?

The number of patients plays a major role, and the lack of resources is a major concern. Also, here, when we train people to take care of patients with highly communicable infections, specifically Ebola and other hemorrhagic fevers, we always say that you can’t be in that heavy protective equipment for more than a short amount of time, and you can’t be on shift for more than four hours. And that’s with one patient, maybe. Now you have docs who are taking care of 40 patients and they’re doing it in seven-hour shifts or even longer. That could definitely contribute to infection among health care workers.

What’s it like to wear that protective equipment? Can it be compared to space suits?

What’s currently being used in the field is a full-body gown, masks, face shields, head covers, double gloves, and then rubber boots with covering booties over them.

All this material is a barrier to any transmission of any fluids, but a lot of times it also, as you can imagine, blocks air exchange and it can get extremely hot, especially given the heat in the countries that we’re talking about. I’ve read accounts from some of the folks who are down there, and you can get very dehydrated; you can lose a lot of your body fluids from being in that protective equipment for a long time.

Is there any new technology that you could bring that could help?

It’s not so much the need for more advanced equipment as much as just needing the proper amount of the equipment they already have down there.

In the US, we have equipment—the space suit you mentioned—which is basically the powered air-purifying respirators—what we call PAPRs—and that’s the headgear you see with the air filter attached to it. The issue with that is, A, it’s expensive—though it would be ideal to get it down there—and B, it requires electricity, and in the field it can be difficult to have a reliable source of electricity.

Do you feel confident that when you go to Sierra Leone, you’ll be able to avoid getting infected?

I think you’re asking me if I’m afraid at all. Yes, I have fears for my safety, I think it would be cavalier not to have a healthy amount of fear, but it’s that fear that drives us to be careful and to follow the protocols. I have extensive training and I have a background in infectious disease and particularly with these pathogens.

I’m reminded of the Hillel quotation, “If not me, then who, and if not now, then when?” The need is great. The health care workers are overwhelmed, and more help can make it safer for everyone involved. I think we all face risks when we walk out in the morning…

14-7999-BHADELIA-( Portrait = Full Name)

Not from Ebola!

Right, but then there are those of us who regularly face risk at work: Firemen leave the station knowing they could get hurt. Police officers patrol the streets knowing there might be a violent altercation. Even regular doctors go to work knowing they’re at risk for exposure to blood-borne pathogens and multi-drug-resistant organisms. But I think it’s very rare that we’re asked to give something back based exactly on our skills and knowledge, and I think I can contribute, and that’s why I’m going.

I also feel strongly about going in order to bring clinical acumen home with me stateside. Although doctors in the US are taught about Ebola, not many of us have seen patients with viral hemorrhagic fevers. The National Emerging Infectious Diseases Laboratory (NEIDL) plans to conduct research with virulent pathogens, including Ebola, and my job is to run the medical response program in the very, very unlikely event of an exposure. My experience in Sierra Leone will allow me to pass along on-the-ground expertise to health care providers locally at Boston Medical Center.

You have those skills and that knowledge. What can other people do?

We can contribute to education and awareness about this infection and what’s real versus what’s irrational fear—in terms of how this virus is transmitted and why it’s a big issue there and less likely to be an issue here.

Two aid workers, Kent Brantley and Nancy Writebol, were infected down there, and usually health care workers are “extracted” and brought home for care, but their extraction was delayed because countries were not allowing the government to fly them through their air space. That’s irrational fear.

Another way would be personal protective equipment: it’s very much needed and I understand the issue is just getting it into the countries and getting it distributed. Those who have the ability to contribute that, that’s a powerful way to help.

And if you’re a health care worker who has experience in caring for patients such as these, or who has training in biosafety procedures, you can volunteer…

So is this Ebola outbreak the shape of the future, somehow?

What comes to my mind is the T. H. Huxley quote: “The question of questions for mankind, the problem that underlies all others, and is more deeply interesting than any other, is the ascertainment of the place which man occupies in Nature, and of his relation to the universe of things.” Huxley was a biologist—he spoke at the time when Darwin was presenting his theory of evolution—and now there are more than 7 billion of us seeing to find balance with our surroundings.

Since 1970, we’ve seen the discovery of over 40 infectious diseases that impact humans. As we become a larger population, we encroach into ecologies we haven’t previously explored; we come into contact with endemic animals and this allows the pathogens to make a cross-species exchange more easily. So if the past 20 or 30 years are any indication, I think this may become more of an issue in the future.

A version of this BU Today story was originally published on WBUR’s CommonHealth blog on Aug. 1, 2014.

Carey Goldberg is the cohost of WBUR’s CommonHealth.  She can be reached at careyg@comcast.net.

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HIV Non-disclosure, Stigma, Incarceration Are Possible Predictors of Poor Follow Up in Research Trials

July 22nd, 2014 in Uncategorized

A collaborative effort between American, Russian and Ukrainian researchers offers new insight into a well-known barrier to high quality, longitudinal HIV research: loss of participant follow up.  This study, led by researchers at the BU Schools of Medicine and Public Health, explored the factors that contributed to attrition in large HIV trial in Russia, a country in which increasing amounts of HIV-related research is being conducted. Their results were published in the June 2014 issue of HIV Clinical Trials.

Any research study that experiences significant loss of participants is at risk for bias: the possibility the missing individuals were not lost randomly.  For example, a medication trial of a 100 people, in which 30 people cannot follow up because they are hospitalized due to severe side effects, will look artificially positive if outcomes data are based on the remaining 70 individuals. Accordingly, the quality of a study will suffer and its findings may be called into question.

This is a particular problem in Russia, as injection drug use (IDU) represents a relatively higher cause of HIV transmission, which has in some studies been associated with factors that negatively impact follow-up: younger age, depression, mental illness, and concomitant alcohol use. However, this has not been a consistent finding, and other relevant factors like HIV non-disclosure status, perceived HIV stigma, and incarceration history have not been thoroughly explored until now.

Tetiana Kiriazova

Tetiana Kiriazova

The researchers analyzed the data from the HIV’s Evolution in Russia – Mitigating Infection Transmission and Alcoholism in a Growing Epidemic (HERMITAGE) study, in which patients were asked to return for six and 12 month assessments.  Of the 660 participants in the study surviving until follow-up, 168 (25.5 percent) did not return for their 12 month follow up visit, and 101 (15.3 percent) never attended any follow-up visit at all, despite extensive retention strategies. Their analysis revealed that participants with current IDU and HIV status non-disclosure missed their first study at approximately 40 percent higher rates than those who did not. They also observed binge drinking was more likely to affect loss to follow up in men than in women, that that a history of incarceration was a stronger predictor of the same in women than in men.

BUSM Postdoctoral Fellow Tetiana Kiriazova, a Ukranian National Institute on Drug Abuse (NIDA) Invest research fellow at the BMC Clinical Addiction Research and Education (CARE) Unit in the department of medicine, and lead author on this study, concluded that “understanding and addressing potential predictor of attrition may improve participant retention in longitudinal clinical research studies of HIV-infected persons, particularly in important but resource-limited research settings.”

Submitted by Ravi Pandit, MD, MPH

 

BUSM MD/PhD Candidate Tracks Osteoarthritis With Nanoparticles

July 11th, 2014 in Uncategorized

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The new osteoarthritis diagnostic method exploits tantalum oxide nanoparticles as contrast agents to image surface and interior regions of cartilage coating the joints.

A chronic disease afflicting more than 27 million Americans and 630 million worldwide, osteoarthritis occurs as the protective cartilage coating on joints in the knees, hips and other parts of the body degrades. No cure for osteoarthritis exists, but treatments can slow its progression, reduce pain and restore joint functioning. Now a team of researchers led by Professor Mark Grinstaff (BME, Chemistry, MSE) has developed a sensitive imaging method that promises to enhance diagnosis of osteoarthritis and enable improved care through earlier detection and more targeted treatments.

The method combines nanotechnology, engineering and medicine, and exploits new, biocompatible nanoparticles as contrast agents to image surface and interior regions of articular cartilage (the smooth, water-rich tissue that lines the ends of bones in load-bearing joints) — regions that traditional X-ray illumination cannot detect. The research, which was funded by the National Institutes of Health, is described in the June 30 issue of Angewandte Chemie.

“In the short term, these contrast agents could be used to image cartilage over time to monitor the efficacy of proposed osteoarthritis drugs,” said Grinstaff. “With continued development, they may enable clinicians to diagnose and stage the disease so that the most appropriate course of treatment could be followed.”

Two members of Grinstaff’s lab, MD/PhD student Jonathan Freedman (Pharmacology) and Postdoctoral Fellow Hrvoje Lusic (BME and Chemistry), synthesized a new nanoparticle contrast agent made of tantalum oxide that diffuses into the cartilage, thus enabling clinicians to use CT-scans to assess cartilage thickness and pinpoint lesions and injuries in osteoarthritic tissue. Guided by their clinical collaborator, Beth Israel Deaconess Medical Center/Harvard Medical School physician Brian Snyder, Freedman and Lusic used the nanoparticles to successfully image rat articular cartilage in in vivo and ex vivo experiments, as well as in a cadaverous finger joint.

They chose tantalum as a contrast agent material because it absorbs a greater fraction of X-rays produced at clinical scanning voltages than traditional materials. In addition, the tantalum nanoparticles’ positive charge automatically directs the particles to the cartilage, which carries a negative charge. Building on their initial success, the researchers plan to conduct additional in vivo experiments in animal models.

The impetus for exploring new and better contrast agents came from Snyder, who sought better ways to diagnose and assess treatment of osteoarthritis. Grinstaff sees the new method as especially promising for early detection of the disease.

“Today we have very poor capability to detect early stage osteoarthritis,” said Grinstaff. “Most patients come into the clinic at stage three when the pain becomes significant, but if diagnostics based on our method is done proactively, many patients could get the treatment they need much earlier and avoid a lot of discomfort.”

Submitted by Mark Dwortzan

BU Researchers and Collaborators Receive $12.6 Million NIH Grant to Study Genetics of Alzheimer’s Disease

July 7th, 2014 in Uncategorized

Researchers from the Biomedical Genetics division of the Boston University School of Medicine (BUSM) are part of a five-university collaboration receiving a $12.6 million, four-year grant from the National Institute on Aging (NIA), part of the National Institutes of Health (NIH), to identify rare genetic variants that may either protect against, or contribute to Alzheimer’s disease risk.

Lindsey Farrer

Lindsey Farrer

At BUSM, the Consortium for Alzheimer’s Sequence Analysis (CASA) is led by Lindsay A. Farrer, PhD, Chief of Biomedical Genetics and professor of medicine, neurology, ophthalmology, epidemiology, and biostatistics, who is the principal investigator. Other Boston University investigators include Kathryn Lunetta, PhD, professor of biostatistics; Gyungah Jun, PhD, assistant professor of medicine, ophthalmology and biostatistics; and Richard Sherva, PhD, research assistant professor of medicine.

CASA investigators will analyze whole exome and whole genome sequence data generated during the first phase of the NIH Alzheimer’s Disease Sequencing Program, an innovative collaboration that began in 2012 between NIA and the National Human Genome Research Institute (NHGRI), also part of NIH. They will analyze data from 6,000 volunteers with Alzheimer’s disease and 5,000 older individuals who do not have the disease. In addition, they will study genomic data from 111 large families with multiple members who have Alzheimer’s disease, mostly of Caucasian and Caribbean Hispanic descent to identify rare genetic variants.

“This is an exciting opportunity to apply new genomic technologies and computational methods to improve our understanding of the biological pathways underlying this disease,” said Farrer. “The genes and pathways we identify as integral to the Alzheimer process may become novel therapeutic targets,” he added.

Alzheimer’s disease, a progressive neurodegenerative disorder, has become an epidemic that currently affects as many as five million people age 65 and older in the United States, with economic costs that are comparable to, if not greater than, caring for those of heart disease or cancer. Available drugs only marginally affect disease severity and progression. While there is no way to prevent this disease, the discovery of genetic risk factors for Alzheimer’s is bringing researchers closer to learning how the genes work together and may help identify the most effective interventions.

This effort is critical to accomplishing the genetic research goals outlined in the National Plan to Address Alzheimer’s Disease, first announced by the U.S. Department of Health and Human Services in May 2012 and updated annually. Developed under the National Alzheimer’s Project Act, the plan provides a framework for a coordinated and concentrated effort in research, care, and services for Alzheimer’s and related dementias. Its primary research goal is to prevent and effectively treat Alzheimer’s disease by 2025.

With the current award, CASA joins the NHGRI Large-Scale Sequencing and Analysis Centers program, an NIH-supported consortium that provides large-scale sequence datasets and analysis to the biomedical community. CASA researchers will facilitate the analyses of all Alzheimer’s Disease Sequencing Project (ADSP) and additional non-ADSP sequence data to detect protective and risk variants for Alzheimer’s disease.

“We are delighted to support the important research being accomplished under this broad-based, collaborative effort. A team effort is vital to advancing a deeper understanding of the genetic variants involved in this complex and devastating disease and to the shared goal of finding targets for effective interventions,” said NIH Director Francis Collins, MD, PhD.

“Alzheimer’s disease research is appropriately one of our highest priorities,” said BUSM Dean Karen Antman, MD “We need more to better understand the genetic and environmental mechanisms that will come in part from CASA to develop more effective treatments or even better, to prevent the disease,” she added.

CASA is a collaboration of Boston University School of Medicine and four other American universities. Jonathan Haines, PhD, will lead the project at Case Western Reserve University; Richard Mayeux, MD, at Columbia University; Margaret Pericak-Vance, PhD, at the University of Miami; Gerard D. Schellenberg, PhD, at the University of Pennsylvania; and Lindsay Farrar, PhD, at Boston University.

This research is supported by the NIA grant UF1-AG047133.

Dental and Medical Students Team Up to Improve Health in East Boston

July 3rd, 2014 in Uncategorized

David Garazi DMD 15 gives an oral health screening to a child as Rifat Malhotra AS 15 records the results

David Garazi DMD 15 gives an oral health screening to a child as Rifat Malhotra AS 15 records the results

Fifteen volunteers from the BU Henry M. Goldman School of Dental Medicine (GSDM) joined together with twelve volunteers from BU School of Medicine (BUSM) to provide health care services to children and their families at the second annual Interprofessional Spring Wellness Fair at the East Boston YMCA for Healthy Kids Day last April 26.

Oral Health Promotion Kathy Lituri and Farhan Khan AS 15 organized GSDM participation in the wellness fair. The GSDM faculty sponsors were Drs. Ana Keohane and Gladys Carrasco. The GSDM student volunteers were: William Alvarez (pre-dental), Michelle DaRocha DMD 15, David Garazi DMD 15, Siavash Golaby Sanajany DMD 15, Farhan Khan AS 15, Jeongyun Kim AS 15, Andrea Lugo (pre-dental), Reefat Malhotra AS 15, Ashish Papneja DMD 15, Abdul Rahman Addas AS 14, Richa Rashmi AS 15, Neeha Sood AS 15, and Bernadette Therriault AS 15. Dr. Suzanne Sarfaty served as the BUSM faculty liaison and Samih Nassif MED 17 was team leader for the medical students.

Despite a rainy day, volunteers were in high spirits and worked efficiently. The GSDM students promoted oral health by offering oral screenings as well as information on oral health topics, such as good oral hygiene practices, healthy eating, prevention of cavities and gum disease, dry mouth, denture care, smoking cessation, and the prevention of oral cancer. GSDM had five tables set up. They provided 26 screenings to children and adults.

The BUSM students offered screenings for blood glucose levels, blood pressure, and cholesterol and measured body mass index. They also provided individualized nutrition information.

Co-organizer Farhan Khan said, “In exchange for a Saturday morning, we believe that we were able to raise awareness and help those individuals make positive health and wellness choices.” Khan continued, “Moreover, we had an excellent opportunity to be active and responsible members in our neighboring community.”

Khan noted that, in addition to giving back to the community, a secondary focus of the wellness fair was to strengthen inter-professional communication between medical and dental students. Their aim is to build a foundation of collaboration, which will be essential in a future of team-based and patient-centered health care.

Dean Jeffrey W. Hutter said, “I am very pleased to see members of the Henry M. Goldman School of Dental Medicine and School of Medicine community joining together for a common cause.” He continued, “Thank you to the volunteers who contributed to the success of this community outreach event.”

Photos are available on Facebook and Flickr.

Adults with Psychiatric Disabilities Benefit from GSDM Outreach

June 30th, 2014 in Uncategorized

Adults with Psychiatric Disabilities Benefit from GSDM Outreach

(l-r) Olga Spival (pre-dental), Marium Qureshi AS 15, and Sai Ramani Krishna Kumar AS 15

Earlier this year, volunteers from BU’s Henry M. Goldman School of Dental Medicine (GSDM) provided services to adults with psychiatric disabilities at the Center Club Boston, a program of Bay Cove Human Services. Led by Oral Health Promotion Director Kathy Lituri and in collaboration with the GSDM student chapter of the American Association of Public Health Dentistry (AAPHD), Sai Ramani Krishna Kumar AS 15, Marium Qureshi AS 15, and Olga Spival (pre-dental) participated in a wellness fair held at the club.

Center Club is a five-day-a-week program for people with psychiatric disabilities. The program combines employment, housing, and education services with social activities, wellness initiatives, and advocacy using a holistic approach and principles of self-help, peer support and empowerment.

The aim of the wellness fair was to increase health awareness through education and prevention. Approximately 250 clients and staff of Bay Cove Human Services attended. Attendees were offered basic health screenings, blood pressure and glucose checks, as well as a variety of informational activities designed to raise awareness of the many health-related programs, services, and providers located in the surrounding community. The GSDM volunteers offered oral health screenings, referrals, and education.

Said Kathy Lituri, “This was an excellent opportunity for students to participate in a community-based event, share their expertise as oral health professionals, and to learn more about the oral health issues that affect adults and their families who live with mental illness, addiction disorders, or developmental disabilities.”

Submitted by GSDM Communications.

Reproduction Later in Life is a Marker for Longevity in Women

June 26th, 2014 in Uncategorized

Women who are able to naturally have children later in life tend to live longer and the genetic variants that allow them to do so might also facilitate exceptionally long life spans.

A Boston University School of Medicine (BUSM) study published in Menopause: The Journal of the North American Menopause Society, says women who are able to have children after the age of 33 have a greater chance of living longer than women who had their last child before the age of 30.

“Of course this does not mean women should wait to have children at older ages in order to improve their own chances of living longer,” explained corresponding author Thomas Perls, MD, MPH. “The age at last childbirth can be a rate of aging indicator. The natural ability to have a child at an older age likely indicates that a woman’s reproductive system is aging slowly, and therefore so is the rest of her body.”

The study was based on analysis of data from the Long Life Family Study (LLFS)—a biopsychosocial and genetic study of 551 families with many members living to exceptionally old ages. Boston Medical Center, the teaching hospital affiliate of BUSM, is one of four study centers that make up the LLFS. The study investigators determined the ages at which 462 women had their last child and how old those women lived to be. The research found that women who had their last child after the age of 33 years had twice the odds of living to 95 years or older compared with women who had their last child by age 29.

The findings also indicate that women may be the driving force behind the evolution of genetic variants that slow aging and decrease risk for age-related genes, which help people live to extreme old age.

“If a woman has those variants, she is able to reproduce and bear children for a longer period of time, increasing her chances of passing down those genes to the next generation,” said Perls, the director of the New England Centenarian Study (NECS), a principal investigator of the LLFS and a professor of medicine at BUSM. “This possibility may be a clue as to why 85 percent of women live to 100 or more years while only 15 percent of men do.”

The results of this study are consistent with other findings on the relationship between maternal age at birth of last child and exceptional longevity. Previously, the NECS found that women who gave birth to a child after the age of 40 were four times more likely to live to 100 than women who had their last child at a younger age.

The results of Perls’ study show the importance of future research on the genetic influences of reproductive fitness because they may also impact a person’s rate of aging and susceptibility to age-related diseases, according to the researchers.

Also contributing to this study were researchers from Boston University School of Public Health, Mailman School of Public Health, Washington University and the University of Pennsylvania.

The Long Life Family Study is funded by the U.S. National Institute on Aging/National Institutes of Health.

The Brown Fat Death Spiral

June 26th, 2014 in Uncategorized

BU-led study explores how a good fat becomes impaired

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Kenneth Walsh, director of the Whitaker Cardiovascular Institute, is the lead author on a study that sheds light on the life and death of brown fat cells and illustrates the important role of brown fat in metabolism. Photo courtesy of Kenneth Walsh

White and brown fat are the yin and yang of metabolism. We’re all familiar with white fat, the squishy stuff that bulges around our waists after a few too many doughnuts. But brown fat is more mysterious. It’s the good twin—it burns energy, produces heat, and may hold clues to combating obesity.

A new study led by Kenneth Walsh, director of the BU School of Medicine’sWhitaker Cardiovascular Institute and a MED professor of medicine, sheds light on the life—and death—of brown fat cells and illustrates the important role that brown fat plays in metabolism.

The study, published in the May Journal of Clinical Investigation, shows that feeding mice a high-fat, high-sugar diet causes their brown fat cells to malfunction, a process that Walsh likens to a “death spiral.” While it’s long been known that humans lose brown fat as they age, the study is the first to describe exactly how brown fat cells “whiten,” effectively becoming more similar to white fat.

“The biggest driver today for cardiovascular disease is obesity and metabolic dysfunction. That’s what’s bringing people into the clinic,” says Walsh. “This study further demonstrates the complex interplay between the cardiovascular and metabolic systems.”

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Normal brown fat (left) loses mitochondria and “whitens” when obesity sets in. Slides courtesy of Kenneth Walsh

White fat looks white because it’s full of molecules called lipids, which the body uses for long-term energy storage. Brown fat has lipids, too, but it is constantly using them like fuel to stoke a fire. Brown fat looks brown because is packed with mitochondria, the tiny cellular powerhouses that burn energy to keep us warm and move our muscles. (White fat, conversely, is not very metabolically active and has fewer mitochondria.) For many years, scientists thought that brown fat existed only in small mammals like mice and in newborn human babies, who need help staying warm.

Then in 2009 scientists found that adults have brown fat, too—a few pockets in their necks and chests. Since lean people have more brown fat than obese people, the scientists suspected that brown fat might somehow play a role in gaining weight or in keeping it off.

“For years brown fat was a scientific backwater, because we thought it was only in fuzzy little animals and babies,” Walsh says. “Suddenly it became part of the adult metabolic equation. Now it’s one of the hottest topics in metabolism.”

But big questions remain: does brown fat play a significant role in adult human metabolism? Can white fat become brown? Why do we lose brown fat as we age? How exactly does brown fat whiten, and is there a way to stop it?

In the study, Walsh and his colleagues tried to tackle the last question: what is happening, on a molecular level, when brown fat turns white? To answer the question, they fed normal mice high-fat, high-sugar mouse chow—much like the average American diet—and let them eat as much as they wanted. After eight weeks, remarkable changes were apparent: the mice had gained weight (white fat, unfortunately) and become insulin-resistant—a precursor to diabetes. And their brown fat, no longer able to burn energy efficiently, had become engorged with lipids. In effect, the brown fat had begun to turn white.

“You take a normal lab mouse, give it a fast-food diet full of fat and sugar, and it throws them out of whack,” says Walsh. “It totally confuses their metabolism.”

Normal brown fat (left) is fed by many blood vessels, seen here in green. In obese mice, blood vessels feeding the brown fat shriveled and disappeared. Slides courtesy of Kenneth Walsh

Normal brown fat (left) is fed by many blood vessels, seen here in green. In obese mice, blood vessels feeding the brown fat shriveled and disappeared. Slides courtesy of Kenneth Walsh

What happened? By studying tissue and blood samples from the mice at different times after starting the fast-food diet, Walsh and his colleagues teased apart the chain of events that led to the demise of brown fat. First, they discovered, the unhealthy diet led to high level of toxic fatty acids in the brown fat. This led to the malfunction of a gene called VEGFA (vascular endothelial growth factor A), which helps control the growth of blood vessels in adult tissues. Without a well-functioning VEGFA gene, blood vessels feeding the brown fat shriveled and disappeared, sharply reducing its blood supply. Deprived of blood, and thus oxygen, the mitochondria in the brown fat cells couldn’t burn lipids efficiently, so the fuel began to pile up. The result: brown fat turned white. “It was a pathological cascade, a death spiral,” Walsh says. “Metabolic dysfunction led to the loss of blood vessels, and blood vessel loss impaired brown fat, leading to more metabolic dysfunction. What was really surprising is that the white fat was minimally affected by blood vessel loss, but the brown fat disintegrated.”

Then came the rescue attempt. Walsh and his colleagues used a virus to insert the gene for VEGFA into the brown fat of obese mice. The infusion of VEGFA didn’t bring the mice back to normal, but it had a restorative effect: the mice’s blood vessels stopped withering, the brown fat perked up and improved its function, and the insulin resistance improved.

It’s too early to say whether this work may eventually lead to new treatments for obesity in humans. But it does shed light on the critical role that the growth and atrophy of blood vessels may play in the maintenance of brown fat, and it demonstrates the rapid tumble toward metabolic dysfunction and obesity once brown fat starts to fail. The new knowledge gives clues for potential targets and treatments. By some predictions, half of the American population will be obese by 2050. To reverse the obesity epidemic, we may need all the clues that science can offer.

This BU Today story was written by Barbara Moran (COM’96) is a science writer in Brookline, Mass. She can be reached through her website WrittenByBarbaraMoran.com.