Category Archives: Uncategorized

Tobias Walther chosen as HHMI Investigator

Tobias_WaltherCongratulations to Tobias Walter, who was chosen from a group of 894 eligible applicants to be one of 26 newly-minted Howard Hughes Medical Institute (HHMI) Investigators!  HHMI investigators will receive the flexible support necessary to move their research in creative new directions. The initiative represents an investment in basic biomedical research of $153 million over the next five years.

The scientists represent 19 institutions from across the United States. The new HHMI investigators – which include three current HHMI early career scientists — were selected for their individual scientific excellence.

HHMI will provide each investigator with his or her full salary, benefits, and a research budget over their initial five-year appointment. The Institute will also cover other expenses, including research space and the purchase of critical equipment. Their appointment may be renewed for additional five-year terms, each contingent on a successful scientific review.

HHMI encourages its investigators to push their research fields into new areas of inquiry. By employing scientists as HHMI investigators — rather than awarding them research grants — the Institute is guided by the principle of “people, not projects.” HHMI investigators have the freedom to explore and, if necessary, to change direction in their research. Moreover, they have support to follow their ideas through to fruition — even if that process takes many years.

Why Public Health? Selasi Dankwa

Selasi-DankwaIn our series “Why Public Health?” we ask Harvard T.H. Chan School of Public Health students and alumni to talk about what drew them to the field. Selasi Dankwa, PhD ’15, took an early interest in infectious diseases like malaria and cholera, a part of everyday life in her home country of Ghana. At Harvard Chan School, she studies the parasites that cause malaria infection. Now she envisions taking her skills and knowledge and returning to Ghana to “make a difference.”

See the video here: Why Public Health? Selasi Dankwa

Malaria parasite’s essential doorway into red blood cells illuminated

malaria Manoj

Malaria parasites infect red blood cells cultured from stem cells

Boston, MA – Researchers at Harvard T. H. Chan School of Public Health and the Broad Institute have identified a protein on the surface of human red blood cells that serves as an essential entry point for invasion by the malaria parasite. The presence of this protein, called CD55, was found to be critical to the Plasmodium falciparum parasite’s ability to attach itself to the red blood cell surface during invasion. This discovery opens up a promising new avenue for the development of therapies to treat and prevent malaria.

Plasmodium falciparum malaria parasites have evolved several key-like molecules to enter into human red blood cells through different door-like host receptors. Hence, if one red blood cell door is blocked, the parasite finds another way to enter,” said senior author Manoj Duraisingh, John LaPorte Given Professor of Immunology and Infectious Diseases at Harvard Chan. “We have now identified an essential host factor which when removed prevents all parasite strains from entering red blood cells.”

The five-year study was carried out in collaboration with labs at Harvard Medical School and the Broad Institute. It appears online May 7, 2015 in Science.

Severe malaria is one of the leading causes of mortality among children globally. During infection, parasites invade and replicate within red blood cells. With resistance to malaria drugs increasing, researchers are desperate to find new ways to prevent and treat the disease.

Lead author Elizabeth Egan, research fellow in the Department of Immunology and Infectious Diseases at Harvard Chan and instructor in pediatrics at Boston Children’s Hospital, and colleagues developed a new technique to tap into a relatively unexplored area — identifying characteristics of a host red blood cell that make it susceptible to the parasites. Red blood cells are difficult targets for such efforts as they lack a nucleus, which makes genetic manipulation impossible.

The researchers transformed stem cells into red blood cells, which allowed them to conduct a genetic screen for host determinants of P. falciparum infection. They found that malaria parasites failed to attach properly to the surface of red blood cells that lacked CD55. The protein was required for invasion in all tested strains of the parasite, including those developed in a laboratory as well as those isolated from patients, making it a primary candidate for intervention.

“The discovery of CD55 as an essential host factor for P. falciparum raises the intriguing possibility of host-directed therapeutics for malaria, as is used in HIV,” said Egan. “CD55 also gives us a hook with which to search for new parasite proteins important for invasion, which could serve as vaccine targets.”

This study was supported by a Gates Foundation Grand Challenges Exploration Award OPP1035276 (M.T.D.), National Institutes of Health (NIH) grant R01AI091787 (M.T.D.), a Pediatric Scientist Development Program Fellowship from the Eunice Kennedy Shriver National Institute of Child Health and Human Development K12-HD000850 (E.S.E), NIH grant K08 1K08AI103034-01A1 (E.S.E.), Boston Children’s Hospital Faculty Development Award (E.S.E.), NIH grant K01DK098285 (J.A.P.), and the Cambridge Biomedical Research Center, UK (M.P.W. and L.V.N.).

“A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion,” Elizabeth S. Egan, Rays H.Y. Jiang, Mischka A. Moechtar, Natasha S. Barteneva, Michael P. Weekes, Luis V. Nobre, Steven P. Gygi, Joao A. Paulo, Charles Frantzreb, Yoshihiko Tani, Junko Takahashi, Seishi Watanabe, Jonathan Goldberg, Aditya S. Paul, Carlo Brugnara, David E. Root, Roger C. Wiegand, John G. Doench, Manoj T. Duraisingh, Science, online May 7, 2015

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Todd Datz

World Malaria Day forum explores public-private partnerships

Malaria ForumThe global community has made gains in fighting malaria, but those advances are tenuous and multi-sector partnerships are needed to eradicate the disease. That was the consensus among experts in the field who gathered at a forum co-hosted by Harvard’s Defeating Malaria initiative  on April 24 to mark World Malaria Day. The event, Partnerships for Malaria Elimination: Lessons and Opportunities, focused on the need to build partnerships between governments, academic researchers, and the private sector.

According to the World Health Organization, there were an estimated 198 million malaria cases in 2013 and an estimated 584,000 deaths. In a video message to the audience at the Joseph B. Martin Conference Center, Ray Chambers, the United Nation’s Secretary-General’s Special Envoy for Malaria, said that progress has been made in fighting the disease: Since 2000, there has been a 58% decrease in child deaths from malaria in Africa. Chambers said more gains are on the horizon.

“Today 55 countries are on target to reduce malaria incidences by 75% by the end of this year, and 26 countries are on a clear path towards elimination,” he said, adding that cooperation at multiple levels will make that possible. “Partnerships have helped drive innovation, improve measurement, and provide the management expertise that strengthens our work. They hold the key to new solutions and new technology.”

Dyann Wirth, Richard Pearson Strong Professor of Infectious Diseases and Chair, Department of Immunology and Infectious Diseases at Harvard T.H. Chan School of Public Health, said that type of holistic approach has driven the work of the Defeating Malaria initiative since its inception in 2011.

“We brought together individuals from across the spectrum of the malaria world, and across Harvard, trying to understand the fundamental aspects of this disease from its biology and transmission, all the way through the social, behavioral, and policy [components] to develop tools to attack the problem.”

Wirth moderated a panel that focused on the unique challenges of providing those tools and interventions in faith-based communities, where there can be tension between traditional healers and technologically focused medical personnel. Panelists discussed the efforts of the NetsforLife project, a partnership with the Episcopal Relief & Development organization, which has provided more than 22 million insecticide-treated mosquito nets across Africa.

Wirth said that the project is an effective convergence of a faith-based approach with a more business-oriented method, bringing a different approach to malaria control than organizations with a medical or health delivery background.  Wirth pointed out that it is a strategy that relies on cooperation and takes into account the multiple factors beyond medical treatment that can affect malaria control efforts.  She believes this community-based approach can help reduce the resistance to those new initiatives.  “Education and knowledge backed up by evidence allows people to see and actually evaluate [interventions] for themselves.”

In addition to implementation of malaria control measures, forum attendees also heard about various technological advances that could allow for more rapid diagnosis of the disease.

The Corporate Alliance for Malaria in Africa and GBCHealth co-sponsored the event.

Curtis Huttenhower wins top junior faculty award in bioinformatics

curtis-huttenhower-nicola-segata-release-copy1Curtis Huttenhower, associate professor of computational biology and bioinformatics, has been named winner of the 2015 Overton Prize from the International Society for Computational Biology. The prize recognizes early or mid-career scientists who are emerging leaders in computational biology and bioinformatics for their accomplishments in research, education, and service.

Huttenhower was chosen for his groundbreaking research on microbial communities, with a focus on the human microbiome. He has worked on developing novel computational tools to analyze the large, complex datasets associated with microbial communities and on the National Institutes of Health Microbiome Project. His research has provided new insights into how microbial communities impact human health and disease.

Huttenhower’s research potential has previously been recognized through two other awards: the Presidential Early Career Award for Scientists and Engineers, and a National Science Foundation Career Award.

Sick with measles, again: Infectious disease expert discusses recent spread, vaccination issues, mor

A bold pathway in life—and biology

Covarrubias-470x313Anthony Covarrubias, PhD ’15, grew up in a working-class neighborhood in South Los Angeles. While celebrities in sports cars whizzed to the beach just a few miles away, Covarrubias’s neighbors waited in long lines at the local health clinic for low-quality care they couldn’t afford. Although his parents worked hard to make ends meet, access to health care and health benefits was not always available. Acutely aware of this disparity from a young age, Covarrubias decided to get an education and help correct the injustice.

For this Harvard T.H. Chan School of Public Health doctoral student, now in his final year in the Biological Sciences program, the quest to cure metabolic diseases is personal. He’s seen family members and neighbors suffer from diabetes and recently learned of a graduate from his high school who died young from atherosclerosis. Finding a cure for conditions that disproportionately shorten the lives of the poor and people of color won’t be easy, but Covarrubias is in it for the long haul.

“Science teaches you to be patient and persevere,” he says. “Sometimes experiments don’t work out. Sometimes we give it our best effort and it’s still not enough. But that’s what I have signed up for.”

Convinced of the power of science

Covarrubias brings a conviction in the power of science to explain the world and make it a better place, as well as an acute awareness of how the pathways in life—as well as in biology—can change.

On a typical day he pulls out a bottle of blue liquid and portions it into a plastic tray indented like an egg carton. In the tray are macrophages—crucial immune system cells. He slides it into a gene sequencing machine and leans in close to the monitor, brow furrowed. Maybe this time the bar graphs filling the screen will unlock the mysteries of his lab-grown samples—and point the way to a cure for diabetes.

Macrophages are frontline troops in the war against infections, surrounding and digesting bacteria and other cellular invaders and secreting chemicals that launch the process of inflammation. In many overweight and obese people, however, macrophages set off a state of chronic inflammation that can usher in a host of metabolic woes, such as diabetes and atherosclerosis.

Yet just as macrophages trigger inflammation, they also can shut it down. And locating the switch that determines whether the cells’ inflammatory or anti-inflammatory pathway is activated could have lifesaving consequences for millions of people.
That’s what Covarrubias hopes to find and learn how to control. “The best part of being a molecular biologist is that we can think of crazy ideas and actually try them,” he says. “Every now and then, one of them works—and that’s what drives me.” One of his most important findings, which linked a protein in a genetically engineered mouse to macrophage activation, was published this past November in Nature Communications.

Lessons from Skid Row

Covarrubias’s family wasn’t poor, but he grew up surrounded by poverty and saw clearly from a young age the ways it can stunt the health and potential of those it touches. Many of his friends dropped out of high school, got hooked on drugs, and joined gangs.

Visiting Los Angeles’s Skid Row as a high school volunteer, he was drawn to talk to the people who call the five-block district of makeshift shelters home. “A lot of them were just like you and me, at one time,” he says. “They had jobs and families who cared about them. But then something happened, like a divorce, a death, or onset of mental illness, which made them lose control of their lives. With some assistance, many of them could get back on track.”

His focus returned to Skid Row as an undergraduate researcher at the University of California, Los Angeles (UCLA), assisting in the data analysis of a health care intervention for drug addicts in the neighborhood. Though he had once considered becoming a doctor to help improve health in his community, the experience introduced him to public health as an avenue for using his passion for science to help improve people’s lives. Here was a way to delve into the causes of disease at their most fundamental level.

Support and healthy competition

UCLA was also an eye-opener in other ways. Even coming from a respected Catholic high school, Covarrubias was behind his more privileged college classmates—including his film-major roommate—in science classes. But he persevered, and eventually formed a study group with other students of color who helped each other succeed. “We realized that together, we had so much more brain power,” he says. The group became a source both of support and of healthy competition. “We always tried to outdo each other,” says Covarrubias. “You’d see your friend get a 97, so you wanted to get a 98.”

At Harvard Chan, Covarrubias helped launch a similar support group for students in his program. The Biological Sciences data club meets regularly to talk about highs and lows of members’ individual research efforts in a social, pressure-free environment. “You could be working in the lab next door to another student and see them every day, but still have no clue what they are doing,” says Covarrubias.

Infectious enthusiasm

His recent findings on the link between metabolism and macrophage activation have opened a new research direction in the lab of Tiffany Horng, his adviser. “It would not have been possible without him,” says Horng, assistant professor of genetics and complex diseases, adding that her lab has also benefited from Covarrubias’ “infectious enthusiasm.”

In Horng, Covarrubias has a mentor who won’t settle for less than the best. He tries to be as encouraging with the students he’s mentored over the years, including those in the Biological Sciences in Public Health Summer Research Program for minority undergraduates.

Covarrubias hopes to someday lead an academic research lab. He’s undaunted by statistics on the glut of graduates competing for dwindling tenure-track positions. “I’m not scared by numbers that say only 30 percent of us will get academic jobs,” he says. “Compared to where I started out, those are really good odds.”

Watch Covarrubias’s Why Public Health? video

Amy Roeder is assistant editor of Harvard Public Health

Photo: Kent Dayton/ Harvard Chan

A Cross-disciplinary Approach to Eradicating Malaria

malariasymposium-55-300x200There is an arsenal of cost-effective tools available to combat malaria but getting people to adhere to treatment regimens can be challenging, said Jessica Cohen, assistant professor of global health, at a symposium focused on “The Last Mile to Malaria Eradication,” held December 4, 2014 in Kresge G3. It was sponsored by the Department of Immunology and Infectious Diseases and the Harvard Institute for Global Health and included a poster session and reception in the FXB Atrium.

This was the second such event sponsored by the cross-Harvard initiative Defeating Malaria: From the Genes to the Globe. This effort brings together experts from different disciplines within the University to address complex issues related to eradicating malaria. Dyann Wirth, who heads the Harvard Malaria Initiative and is also Richard Pearson Strong Professor and chair, Department of Immunology and Infectious Diseases, called the Defeating Malaria initiative “a transformational way to focus on major public health problems.”

Cohen discussed the challenges of increasing use of bed nets, which provide protection for people while they sleep against malaria-carrying mosquitos. Some people don’t use them properly; others don’t use them at all and subject themselves to hungry mosquitos looking for a blood meal.

She also noted the challenge of getting patients to finish all of their malaria medication. Often they stop taking it because they think that when they start feeling better that they are cured, or if they continue to feel sick during treatment, they blame the medicine and stop taking it. Others may decide to save pills for later for themselves or other family members.

When people don’t finish their medication, they can have lingering parasites. This can lead to reccurrence of the malaria infection and can accelerate the emergence of resistance (i.e. the parasite becoming resistant to the medication). “This is dangerous because we don’t have any other very effective malaria medications available if the current one fails,” she said.

In a test group in Africa, Cohen and her colleagues found when they experimented with adding simple stickers to bottles of medication that read “Malaria is not gone until all tablets are finished,” that compliance to the regimen increased about 7%. They also are experimenting to see if more attractive and simplified medication packaging will help.

Nick Baro of the Wirth Lab, with master’s student Francisco Cai.

Postdoctoral fellow Nick Baro discusses poster with student Francisco Cai.

According to the World Health Organization’s World Malaria Report for 2014 released on December 9, 2014, 3.2 billion people in 97 countries and territories are at risk of being infected with malaria. In 2013, there were an estimated 198 million malaria cases worldwide and an estimated 584,000 deaths. Ninety percent of the deaths occurred in Africa. The disease killed an estimated 453,000 children under five years of age.

“We’ve made tremendous progress over the last 50 years thanks to the global investment that has led to a remarkable scale up of key interventions, but we’re not anywhere close to the last mile in many countries,” said speaker Günther Fink, associate professor of international health economics. Over the last 150 years, about half the world’s countries have eliminated malaria, he said. “Fifty percent of the world lives malaria-free, but this means 50% of the world still has malaria. We need new tools and we need to move fast.”

Perrine Marcenac, PhD student, with Kristine Werling, and Douglas Paton, research fellow from the University of Perugia.

From left to right: Doctoral student Perrine Marcenac, student Kristine Werling, and Douglas Paton, research fellow from the University of Perugia, at the poster session.

While global incidence of malaria is down, in parts of Africa it’s up, said Barry Bloom, Harvard University Distinguished Service Professor and Joan L. and Julius H. Jacobson Professor of Public Health. Fifty-nine countries are expected to meet the United Nations’ malaria reduction targets by 2015 and more than 50 will exceed the targets. “Only 18 countries are responsible for 80% of the cases,” he said. Most deaths from malaria occur in the Democratic Republic of the Congo and Nigeria.

Matthias Marti, associate professor of immunology and infectious diseases, co-hosted the symposium and Michael Reich, Taro Takemi Professor of International Health Policy, was a moderator. Other speakers included Caroline Buckee, assistant professor of epidemiology; Marcia Castro, associate professor of demography; Flaminia Catteruccia, associate professor of immunology and infectious diseases; Manoj Duraisingh, professor of immunology and infectious diseases, and Sarah Volkman, principal research scientist.

Support for the symposium included ExxonMobil, Bill & Melinda Gates Foundation, Sumitomo Chemical, MCJ/Amelior Foundation, and Malaria No More.

– Marge Dwyer

photos: Craig LaPlante

Symposium Gathers Experts on Homeostatic Regulation

JBL-Hotamisligil-Little-Boice-470x313-470x313November 3, 2014 — Cutting-edge work on homeostatic regulation—the process through which the human body maintains stability in response to changes in external conditions—was the focus at the 17th annual John B. Little Symposium, held October 24-25, 2014 at Harvard School of Public Health (HSPH).

About 180 attendees heard from numerous experts in the field, who discussed topics ranging from radiation epidemiology to fat synthesis and storage to how certain genes and small molecules extend lifespan. HSPH faculty presenters at the symposium included Robert Farese, professor of genetics and complex diseases, and Gökhan Hotamisligil, chair of the Department of Genetics and Complex Diseases.

Robert Farese

HSPH’s Robert Farese discusses fat synthesis and storage in lipid droplets.

The John B. Little Symposium is hosted each year by the John B. Little (JBL) Center for Radiation Sciences and Environmental Health. Both the symposium and the center are named for John B. Little, James Steven Simmons Professor of Radiobiology Emeritus, one of the first scholars to characterize problems in public health as interactions between environmental stressors and humans’ response to those stressors.

In his introduction to the symposium, Hotamisligil praised Little as the “inspirational leader in our department, and father of this field, and father of the symposium.” Little was on hand to welcome attendees.

Both Hotamisligil and Dean for Academic Affairs David Hunter, who gave opening remarks, also acknowledged the support of alumnus Gerald Chan, SM ’75, SD ’79, a former student of Little’s and a director of the Morningside Foundation. The Foundation and Dr. Chan have provided crucial support for the JBL center and the symposium. They also supported the establishment in 2012 of the Morningside Professorship in Radiobiology, in honor of Little. In September of this year, the Morningside Foundation and the Chan family gave HSPH a transformational gift of $350 million in unrestricted endowment—the largest single donation in Harvard’s history and, according to Hunter, the 6th largest to any university in the world. In acknowledgement of the gift, the School will be renamed the Harvard T.H. Chan School of Public Health, in honor of Gerald Chan’s father.

Hunter also announced that the JBL Center will become a school-wide collaboration among the Department of Genetics and Complex Diseases (its current home), the Department of Environmental Health, and the Department of Epidemiology. Hunter said the move is being made possible by a generous gift from an international donor.

This year’s symposium was organized by Zhi-Min Yuan, professor of radiobiology and director of the JBL Center; James Mitchell, associate professor of genetics and complex diseases; and Brendan Manning, professor of genetics and complex diseases.

Karen Feldscher

photos: Tony Rinaldo