Newss RSS Feed

Camilli Research Featured on Schaecter Blog

Tue, 07 May 2013 00:00:00 -0400

MSTP Director Schwob Appointed to NIH Council of Councils

Tue, 07 May 2013 00:00:00 -0400

CTS Director Kent Authors NEJ Editorial

Fri, 03 May 2013 00:00:00 -0400

Sackler Faculty Receive Tufts Collaborates Awards

Thu, 02 May 2013 17:59:00 -0400

Sackler is well-represented in the group of talented Tufts faculty recognized with Tufts Collaborates Awards this year. The Sackler recipients are:

Li Zeng, CMDB and Eric Miller, TUSE for their project "Combining Near Infrared Fluorescence Imaging and MicroCT Technology for Real-Time Detection of Joint Damage in Osteoarthritis"
Pamela Yelick, CMDB, Genetics and Michael Levin (A&S) for their project "Establishing Transgenic Zebrafish to Model Voltage and Ion Level Changes during Craniofacial Development"
Xingmin Sun, TCSVM and Saul Tzipori, CMP, for their project "Novel Chimeric Vaccine against Clostridium Difficile Infection (CDI)"
Ana Soto, CMDB, Carlos Sonnenschein, CMDB, Irene Georgakoudi, TUSE, Mark Cronin-Golomb, TUSE, for their project "Biomechanics of Tissue Organization in Breast Development and Cancer"
Peter Juo, CMP, Neuroscience, Athar Chishti, CMP, Molecular Microbiology, and Larry Feig, Biochemistry, Neuroscience, for their project "Investigating the Role of Kinesin KIF13 Family Motors in Regulating Glutamate Receptor Trafficking and Function in the Mammalian Nervous System"
Dakshina Jandhyala, TUSM, David Kaplan, CMDB and Teresa DesRochers, CMDB Aluma and TUSE, for their project "Studying Shiga Toxin-Mediated Disease Using a Three-Dimensional Renal Tubule Organ Model"
Miaofen Hu, TUSM and Richard Van Etten, CMP, Genetics, Immunology, for their project "The Role of Cdk6 in Chronic Myeloid Leukemia"
Daniel Hannon, TUSE, Karina Meiri, CMDB, Neuroscience, PPET, Katherine Malanson, Neuroscience Alumna, Leslie Schneider, TUSE, Akash Gupta, TUSE, for their project "Investigations into a Collaboration and Assessment Environment for the Great Diseases Curriculum"
Bree Aldridge, Molecular Microbiology and Irene Georgakoudi, TUSE, for their project "Single-Cell Assays of Mycobacterial Metabolic State"

Sackler Researchers Reveal New Genetic Insights

Tue, 30 Apr 2013 00:00:00 -0400

Camilli Study Featured on YouTube

Tue, 23 Apr 2013 00:00:00 -0400

Sackler Faculty Member Receives NSF Career Award

Wed, 17 Apr 2013 00:00:00 -0400

Technology Transfer Internship Program

Wed, 03 Apr 2013 00:00:00 -0400

Beginning in September 2013, Tufts Tech Transfer will offer an internship opportunity to two Tufts University graduate or postdoctoral researchers. We are seeking applicants for a paid technology transfer internship that will require 4 to 6 hours per week from September 2013 through May 2014. Interested candidates should submit application materials to nina.green@tufts.edu. Application deadline is June 7, 2013. Please visit Tufts Tech Transfer website for more information.

Tufts Public Health Celebrates National Public Health Week

Sat, 30 Mar 2013 14:06:00 -0400

Tufts Public Health is sponsoring a series of lectures, information sessions and panels to celebrate National Public Health Week (April 1 - April 5).

Check the Sackler Calendar for these events and learn more about the program by visiting the Public Health Week 2013 Activities webpage.

Sackler Alums and Faculty Transform High School Science Ed

Tue, 26 Mar 2013 00:00:00 -0400

BOSTON (March 26, 2013) — A research paper published online this month in Academic Medicine highlights the successful development, implementation, and effects of an infectious disease curriculum that has now been piloted in five Boston Public Schools. Student engagement and interest in the infectious disease material increased after the curriculum was implemented. Based on pre-and post-tests, student understanding of the course content more than doubled regardless of gender or ethnicity, also attitudes and self-efficacy toward the material improved compared to other students.

The curriculum is part of the Great Diseases Project, a collaboration between researchers at Tufts University School of Medicine and teachers at Boston Public Schools, designed to teach teenagers about real scientific methods and health-related concepts, with the goal of increasing scientific and health literacy.

The study reports that the infectious disease curriculum increased student engagement, science literacy, and critical thinking in the 11th and 12th grade students who participated in the pilot program in Boston schools. Importantly, it also developed the teachers’ knowledge and self-confidence with the new course material and strengthened the researchers’ science communication skills. By the end of the 2013 academic year, the Great Disease modules will have enrolled close to 850 students from schools in Massachusetts, Virginia, and Ohio.

In its 2011 framework for science education, the National Academy of Sciences reported that science education standards must change so that students are exposed to authentic scientific ideas and practices. While the national effort to refine standards is ongoing, the success of the Great Diseases Project contributes to models for development and implementation of science classes to meet the improved standards.

“How science is taught in high school differs greatly from how it is carried out in a real-life laboratory. Our curriculum teaches critical thinking, based on scientific inquiry as it is actually practiced in laboratories around the world,” said Karina F. Meiri, PhD, professor at Tufts University School of Medicine, and member of the Cell, Molecular & Developmental Biology; Pharmacology & Experimental Therapeutics; and Neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts. “Not only that, but health science is usually taught as part of the physical education curriculum. It is not surprising therefore that high school students lack the up-to-date information that would help them make health-related decisions.”

“Our approach is effective because researchers and teachers partnered to develop life-relevant content that engaged students, and because it provides teachers with intensive support as they themselves learn to teach this very novel content,” she continued.

The infectious disease curriculum, which takes a full semester of class time, was designed by biology teachers from two Boston Public Schools teaching students at very different paces, along with Tufts faculty, postdoctoral researchers, and medical students. The group met regularly to identify the core concepts for the infectious disease curriculum, based on national and state science education standards.

After core concepts were determined, the Tufts team developed an intensive series of seminars to prepare the teachers to develop the infectious disease course. The teachers, with support from Tufts researchers, then worked together to create individual lesson plans and activities targeted to the 11th and 12th grade biology students at Boston Latin School and at Madison Park Technical and Vocational High School.

“A major issue in the high-stakes testing environment of high schools is the tension between covering a wide range of topics (breadth) and learning deeply about each topic (depth). Most high school biology textbooks don't teach infectious disease in a way that students can apply it to their lives. Our new curriculum helps students at all academic levels to understand what causes disease, what causes diseases to spread, and how our bodies fight these diseases,” said Gene Roundtree, MEd, a biology teacher at Madison Park Technical and Vocational High School, who used the curriculum in his remedial MCAS classroom. “I believe our curriculum is successful because every lesson is a unique challenge – students participate in labs, debates, competitive card games, and even an auction as part of the curriculum.”

“One of the goals of the Great Diseases curriculum is to create and maintain teenagers’ interest in science as it relates to medicine and disease,” said co-author Kathleen Bateman, MEd, director of mathematics and science at Boston Latin School. “We created interest by selecting subjects that are reflected in the students’ lives – colds, flu, MRSA, and other infectious diseases. The students stay engaged because they work in teams to formulate questions and critically evaluate data, much as they would in an actual laboratory. The new curriculum, organized around diseases, combines best practices in science education with the hands-on experience of medical school and laboratory researchers.”

“One of the challenges of making curricula effective is creating a system of teacher support that will ensure implementation. When content and lesson materials are novel and complex, teachers need to have confidence in their understanding of the new material. We created a comprehensive support system for the teachers and avoided embedding concepts and pedagogy into materials that we did not fully explain,” said first author Berri Jacque, PhD, a 2010 graduate in immunology of the Sackler School of Graduate Biomedical Sciences at Tufts and research assistant professor at Tufts University School of Medicine.

The comprehensive support system involved pairing teachers with Tufts specialists for mentoring. Tufts researchers provided models that enabled each teacher to visualize how classroom discussions could evolve and provided video of teachers implementing the curriculum in a classroom. The comprehensive support system increased teachers’ self-efficacy and their knowledge of the course content. The Tufts medical and Ph.D. students, and postdoctoral fellows, improved their understanding of how to transfer scientific knowledge through the process of developing the seminars and the related material for the teachers.

The infectious disease curriculum is the first of four health-related curricula in the Great Diseases Project that also include other “great diseases” relating to neurological disorders, metabolic disease, and cancer. Each module uses a range of teaching strategies, including labs, case-based studies, and multimedia presentations.

This research is supported by award numbers R25RR026012 from the National Center for Research Resources and R25OD010953 from the Office of the Director, both of the National Institutes of Health.

Additional authors include Katherine Malanson, PhD, a graduate of the neuroscience program at the Sackler School of Graduate Biomedical Sciences at Tufts and post-doctoral fellow with the Great Diseases Project, Tufts University School of Medicine; Bob Akeson, MEd, biology teacher at Boston Latin School; Amanda Cail, MEd, biology teacher at Madison Park Technical and Vocational High School; Chris Doss, MEd, former biology teacher at Boston Latin School now at Stanford; Matt Dugan, MEd, biology teacher at Madison Park Technical and Vocational High School; Brandon Finegold, MEd, formerly a biology teacher at Madison Park Technical and Vocational High School; Aimee Gauthier, MEd, and Mike Galego, MEd, both biology teachers at Boston Latin School; and Lawrence Spezzano, MSc, MEd, biology teacher at Boston Latin School.

Jacque B, Malanson K, Bateman K, Akeson B, Cail A, Doss C, Dugan M, Finegold B, Gauthier A, Galego M, Roundtree E, Spezzano L, Meiri KF. (May 2013). The Great diseases project: A partnership between Tufts medical school and the Boston public schools. Acad Med. 88: 620-625.

###

If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at Tufts University School of Medicine or another Tufts health sciences researcher, please contact please contact Jennifer Kritz at 617-636-3707 or Siobhan Gallagher at 617-636-6586.

Key Role for Glia in Stroke Uncovered

Wed, 13 Mar 2013 00:00:00 -0400

BOSTON (March 18, 2013) — New research published in the Journal of Neuroscience suggests that modifying signals sent by astrocytes, our star-shaped brain cells, may help to limit the spread of damage after an ischemic brain stroke. The study in mice, by neuroscientists at Tufts University School of Medicine, determined that astrocytes play a critical role in the spread of damage following stroke.

The National Heart Foundation reports that ischemic strokes account for 87% of strokes in the United States. Ischemic strokes are caused by a blood clot that forms and travels to the brain, preventing the flow of blood and oxygen.

Even when blood and oxygen flow is restored, however, neurotransmitter processes in the brain continue to overcompensate for the lack of oxygen, causing brain cells to be damaged. The damage to brain cells often leads to health complications including visual impairment, memory loss, clumsiness, moodiness, and partial or total paralysis.

Research and drug trials have focused primarily on therapies affecting neurons to limit brain cell damage. Phil Haydon’s group at Tufts University School of Medicine have focused on astrocytes, a lesser known type of brain cell, as an alternative path to understanding and treating diseases affecting brain cells.

In animal models, his research team has shown that astrocytes—which outnumber neurons by ten to one—send signals to neurons that can spread the damage caused by strokes. The current study determines that decreasing astrocyte signals limits damage caused by stroke by regulating the neurotransmitter pathways after an ischemic stroke.

The research team compared two sets of mice: a control group with normal astrocyte signaling levels and a group whose signaling was weakened enough to be made protective rather than destructive. To assess the effect of astrocyte protection after ischemic strokes, motor skills, involving tasks such as walking and picking up food, were tested. In addition, tissue samples were taken from both groups and compared.

“Mice with altered astrocyte signaling had limited damage after the stroke,” said first author Dustin Hines, PhD, a post-doctoral scholar in the department of neuroscience at Tufts University School of Medicine. “Manipulating the astrocyte signaling demonstrates that astrocytes are critical to understanding the spread of damage following stroke.”

“Looking into ways to utilize and enhance the astrocyte’s protective properties in order to limit damage is a promising avenue in stroke research,” said senior author Phillip Haydon, PhD Haydon is the Annetta and Gustav Grisard professor and chair of the department of neuroscience at Tufts University School of Medicine and a member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health, both of the National Institutes of Health under award numbers R01NS037585 and R01MH095385, respectively. Dustin Hines was partially funded by the Heart and Stroke Foundation of Canada. Haydon is the co-founder and president of GliaCure Inc., which has licensed a pending patent application filed by Tufts University related to work described in this paper.

Hines DJ, Haydon PG. 2013. Inhibition of a SNARE-sensitive pathway in astrocytes attenuates damage following stroke. J Neurosci. 33: 4234-4240.

###

you are a member of the media interested in learning more about this topic, or speaking with a faculty member at Tufts University School of Medicine or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586.

Sackler Shines at the New England Science Symposium

Thu, 07 Mar 2013 00:00:00 -0500

Sackler numbers were strong at the New England Science Symposium held Saturday March 2nd at Harvard Medical School.

Planning Committee:
Dennise de Jesus, Molecular Microbiology Program
Jennifer Nwankwo, Pharmacology & Experimental Therapeutics Program (moderator)
Eydith Comenencia Ortiz, PhD, Neuroscience Alum (moderator)

Judges:
Dan Jay, PhD
Naomi Rosenberg, PhD, Dean
Henry Wortis, MD

Presenters:
Seblewongel Asrat, Molecular Microbiology - MERGE-ID*
David Cantu, TEACRS postdoctoral fellow
Asanta Hatcher, PREP scholar
Ryan Salvador, Immunology Program
Vanessa Yanez, PREP scholar

*Congratulations to Seble Asrat, 3rd place winner for her poster in the Microbiology, Immunology, Genetics and Molecular Biology Category!

Other attendees from Tufts University:

Judge: Jordan Dimitrakoff, MD, PhD, School of Medicine
Presenters: Christopher Boyson, A&S, Rachel Rivero, A&S, Olena Tokareva, PhD, Engineering
Participants: Dawit Bezabih, School of Medicine, Jasmine Robinson, A&S

More information about the symposium

Groundbreaking cholera research featured

Wed, 27 Feb 2013 14:36:00 -0500

Sackler Team Discovers Phage Immune System

Wed, 27 Feb 2013 13:28:00 -0500

BOSTON (February 27, 2013, 1:00 pm ET) — A study published today in the journal Nature reports that a viral predator of the cholera bacteria has stolen the functional immune system of bacteria and is using it against its bacterial host. The study provides the first evidence that this type of virus, the bacteriophage (“phage” for short), can acquire a wholly functional and adaptive immune system.

The phage used the stolen immune system to disable – and thus overcome – the cholera bacteria’s defense system against phages. Therefore, the phage can kill the cholera bacteria and multiply to produce more phage offspring, which can then kill more cholera bacteria. The study has dramatic implications for phage therapy, which is the use of phages to treat bacterial diseases. Developing phage therapy is particularly important because some bacteria, called superbugs, are resistant to most or all current antibiotics.

Until now, scientists thought phages existed only as primitive particles of DNA or RNA and therefore lacked the sophistication of an adaptive immune system, which is a system that can respond rapidly to a nearly infinite variety of new challenges. Phages are viruses that prey exclusively on bacteria and each phage is parasitically mated to a specific type of bacteria. This study focused on a phage that attacks Vibrio cholerae, the bacterium responsible for cholera epidemics in humans.

Howard Hughes Medical Institute investigator Andrew Camilli, Ph.D., of Tufts University School of Medicine led the research team responsible for the surprising discovery.

First author Kimberley D. Seed, PhD, a postdoctoral fellow in Camilli’s lab, was analyzing DNA sequences of phages taken from stool samples from patients with cholera in Bangladesh when she identified genes for a functional immune system previously found only in some bacteria (and most Archaea, a separate domain of single-celled microorganisms).

To verify the findings, the researchers used phage lacking the adaptive immune system to infect a new strain of cholera bacteria that is naturally resistant to the phage. The phage were unable to adapt to and kill the cholera strain. They next infected the same strain of cholera bacteria with phage harboring the immune system, and observed that the phage rapidly adapted and thus gained the ability to kill the cholera bacteria. This work demonstrates that the immune system harbored by the phage is fully functional and adaptive.

“Virtually all bacteria can be infected by phages. About half of the world’s known bacteria have this adaptive immune system, called CRISPR/Cas, which is used primarily to provide immunity against phages. Although this immune system was commandeered by the phage, its origin remains unknown because the cholera bacterium itself currently lacks this system. What is really remarkable is that the immune system is being used by the phage to adapt to and overcome the defense systems of the cholera bacteria. Finding a CRISPR/Cas system in a phage shows that there is gene flow between the phage and bacteria even for something as large and complex as the genes for an adaptive immune system,” said Seed.

“The study lends credence to the controversial idea that viruses are living creatures, and bolsters the possibility of using phage therapy to treat bacterial infections, especially those that are resistant to antibiotic treatment,” said Camilli, professor of Molecular Biology & Microbiology at Tufts University School of Medicine and member of the Molecular Microbiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts University.

Camilli’s previous research established that phages are highly prevalent in stool samples from patients with cholera, implying that phage therapy is happening naturally and could be made more effective. In addition, a study published by Camilli in 2008 determined that phage therapy works in a mouse model of cholera intestinal infection.

The team is currently working on a study to understand precisely how the phage immune system disables the defense systems of the cholera bacteria. This new knowledge will be important for understanding whether the phage’s immune system could overcome newly acquired or evolved phage defense systems of the cholera bacteria, and thus has implications for designing an effective and stable phage therapy to combat cholera.

Additional authors are David W. Lazinski, PhD, senior research associate in the Camilli lab at Tufts University School of Medicine, and Stephen B. Calderwood, MD, Morton N. Swartz, MD academy professor of medicine at Harvard Medical School, and chief, division of infectious disease and vice-chair, department of medicine at Massachusetts General Hospital.

Research reported in this publication was supported by the National Institute of Allergies and Infectious Diseases of the National Institutes of Health under award numbers R01AI55058, R01AI045746, and R01AI058935.

Seed KD, Lazinski DW, Calderwood SB, Camilli A. 2013. A bacteriophage encodes its own CRISPR/Cas adaptive response to evade host innate immunity. Nature 494: 489-491.

Aldridge Featured in Tufts Daily

Wed, 27 Feb 2013 12:39:00 -0500

CTSI Announces Grant Writing Workshop

Tue, 26 Feb 2013 00:00:00 -0500

Tufts CTSI has announced a 5-part workshop to assist with the NIH grant writing process. Consider taking advantage of this series.

Session One: March 11
Session Two: March 18
Session Three March 25
Session Four: April 1
Session Five: April 8

Watch the Sackler Calendar for updates of topics and location.

You must register to attend but there is no fee.

Registration:

Aldridge Named Sloan Fellow

Thu, 14 Feb 2013 00:00:00 -0500

BOSTON (February 14, 2013) — Bree Aldridge, PhD, has been awarded a two-year, $50,000 research fellowship from the Alfred P. Sloan Foundation aimed at encouraging promising young scholars. Aldridge is an assistant professor in molecular biology and microbiology at Tufts University School of Medicine, a member of the Molecular Microbiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts, and adjunct assistant professor in biomedical engineering at Tufts University School of Engineering. Her research work is focused on tuberculosis.

The World Health Organization reports about one-third of the world’s population is infected with tuberculosis. Of that number, only a small number will become sick. In 2011, 8.7 million people became ill and 1.4 million died from tuberculosis. Despite efforts to simplify treatment strategies, tuberculosis still requires months of multi-drug therapy to cure.

Aldridge’s research combines microbiology and engineering approaches to understand the virulence and survival strategies of the bacterium that cause tuberculosis. By working with a multidisciplinary team of researchers to combine molecular approaches with mathematical modeling, she hopes to shorten and simplify treatments for tuberculosis.

Aldridge is one of 126 researchers from the United States and Canada selected to become a 2013 Alfred P. Sloan Research Fellow. Sloan Research Fellows are nominated by their peers and chosen by a distinguished panel of senior scholars.

The Sloan Research Fellowships stimulate fundamental research by early-career scientists and scholars of outstanding promise. Since their inception in 1955, 39 Fellows have been awarded the Nobel Prize in their respective fields and 63 have been awarded the National Medal of Science.

The Alfred P. Sloan Foundation is a philanthropic, not-for-profit institution based in New York City. It was established in 1934 by Alfred Pritchard Sloan, Jr, then president and chief executive officer of the General Motors Corporation.

Tufts CTSI Launches Profiles

Thu, 14 Feb 2013 00:00:00 -0500

Tufts CTSI is delighted to announce the launch of Profiles, a free, web-based research networking tool designed to promote collaboration among scientists and researchers.

Tufts CTSI Profiles is a publicly accessible library of web-based electronic curriculum vitae (CVs) and information about research at Tufts. In this first phase, nearly 1,400 people from 42 different institutions appear in Profiles, including Tufts CTSI and Tufts University faculty members. These initial profiles were created from data derived from the Tufts University Office of Faculty Affairs records and the PubMed database, and then fed directly into Profiles. Researchers can use Profiles to find potential collaborators, co-authors, and mentors.

”Collaboration is key to effective translational research – research that has impact – and Profiles is a fantastic tool to develop collaborations across people, research groups, and disciplines,” says Harry P. Selker, MD, MSPH, Dean of Tufts CTSI. “I hope researchers and students will use this online system to learn about the amazing span of Tufts faculty expertise and to develop new collaborations across Tufts, and beyond.”

Tufts CTSI Profiles will expand as more researchers are included during the coming months.

Profiles is available here

Maguire Video Featured in Tufts News

Wed, 13 Feb 2013 09:48:00 -0500

Sackler Group Identifies Possible Target for Depression Therapy

Tue, 22 Jan 2013 00:00:00 -0500

BOSTON (January 23, 2013) — Neuroscience researchers from Tufts University have found that our star-shaped brain cells, called astrocytes, may be responsible for the rapid improvement in mood in depressed patients after acute sleep deprivation. This in vivo study, published in the current issue of Translational Psychiatry, identified how astrocytes regulate a neurotransmitter involved in sleep. The researchers report that the findings may help lead to the development of effective and fast-acting drugs to treat depression, particularly in psychiatric emergencies.

Drugs are widely used to treat depression, but often take weeks to work effectively. Sleep deprivation, however, has been shown to be effective immediately in approximately 60% of patients with major depressive disorders. Although widely-recognized as helpful, it is not always ideal because it can be uncomfortable for patients, and the effects are not long-lasting.

During the 1970s, research verified the effectiveness of acute sleep deprivation for treating depression, particularly deprivation of rapid eye movement sleep, but the underlying brain mechanisms were not known.

Most of what we understand of the brain has come from research on neurons, but another type of largely-ignored cell, called glia, are their partners. Although historically thought of as a support cell for neurons, the Phil Haydon group at Tufts University School of Medicine has shown in animal models that a type of glia, called astrocytes, affect behavior.

Haydon’s team had established previously that astrocytes regulate responses to sleep deprivation by releasing neurotransmitters that regulate neurons. This regulation of neuronal activity affects the sleep-wake cycle. Specifically, astrocytes act on adenosine receptors on neurons. Adenosine is a chemical known to have sleep-inducing effects.

During our waking hours, adenosine accumulates and increases the urge to sleep, known as sleep pressure. Chemicals, such as caffeine, are adenosine receptor antagonists and promote wakefulness. In contrast, an adenosine receptor agonist creates sleepiness.

“In this study, we administered three doses of an adenosine receptor agonist to mice over the course of a night that caused the equivalent of sleep deprivation. The mice slept as normal, but the sleep did not reduce adenosine levels sufficiently, mimicking the effects of sleep deprivation. After only 12 hours, we observed that mice had decreased depressive-like symptoms and increased levels of adenosine in the brain, and these results were sustained for 48 hours,” said first author Dustin Hines, PhD, a post-doctoral fellow in the department of neuroscience at Tufts University School of Medicine (TUSM).

“By manipulating astrocytes we were able to mimic the effects of sleep deprivation on depressive-like symptoms, causing a rapid and sustained improvement in behavior,” continued Hines.

“Further understanding of astrocytic signaling and the role of adenosine is important for research and development of anti-depressant drugs. Potentially, new drugs that target this mechanism may provide rapid relief for psychiatric emergencies, as well as long-term alleviation of chronic depressive symptoms,” said Naomi Rosenberg, PhD, dean of the Sackler School of Graduate Biomedical Sciences and vice dean for research at Tufts University School of Medicine. “The team’s next step is to further understand the other receptors in this system and see if they, too, can be affected.”

Senior author, Phillip G. Haydon, PhD, is the Annetta and Gustav Grisard professor and chair of the department of neuroscience at Tufts University School of Medicine (TUSM). Haydon is also a member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

Additional authors are Luke I. Schmitt, BS, a PhD candidate in neuroscience at the Sackler School; Rochelle M. Hines, PhD, a post-doctoral fellow in the department of neuroscience at TUSM; and Stephen J. Moss, PhD, a professor of neuroscience at Tufts University School of Medicine and a member of the neuroscience program faculty at the Sackler School.

Hines DJ, Schmitt LI, Hines RM, Moss SJ, Haydon PG. 2013. Antidepressant effects of sleep deprivation require astrocyte-dependent adenosine mediated signaling. Transl Psychiatry Epub ahead of print.

This research was supported by award number R01MH095385 from the National Institute of Mental Health, part of the National Institutes of Health, as well as by award number R01NS037585 from the National Institute of Neurological Disorders and Stroke, both of the National Institutes of Health. Dustin Hines was partially funded by the Heart and Stroke Foundation of Canada. Haydon is co-founder and president of GliaCure Inc., which has licensed a pending patent application filed by Tufts University claiming compounds that modulate the signaling cascades, and related methods of use, described in this paper.

###

If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine or another Tufts health sciences researcher, please contact Siobhan Gallagher at 617-636-6586.

Tufts to Offer Tech Transfer Internships

Tue, 22 Jan 2013 00:00:00 -0500

Tufts University is offering two technology transfer internships beginning July 2013 that require four to six hours of time per week. Interested students should review this opportunity and discuss it with their thesis advisor.

Download the pdf to learn more.

Isberg Featured in PNAS QnA

Mon, 07 Jan 2013 00:00:00 -0500

Ralph Isberg, PhD, a member of the Sackler School programs in Molecular Microbiology and Genetics, and a Professor of Molecular Biology and Microbiology at TUSM was featured in the QnA section of the Proceedings of the National Academy of Sciences, USA.

In the piece, Dr. Isberg discusses his group's recent work on Legionella and newly defined strategies used by the organism that are important for pathogenesis.

Dr. Isberg is a member of the National Academy and an Investigator of the Howard Hughes Medical Institute.

Read the full interview.

Haydon Research Highlighted by NIDA

Mon, 17 Dec 2012 00:00:00 -0500

Key Role for Mitochondria in Inflammation Suggested

Mon, 17 Dec 2012 00:00:00 -0500

BOSTON (December 17, 2012) — Many illnesses, including psoriasis, include inflammatory responses that occur without an apparent infection and worsen with stress. In a study using cultured human mast cells in vitro and in rats, researchers from Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University identified mitochondrial particles — secreted from live, activated mast cells — as a possible trigger of the inflammation that is common in such illnesses.

Mast cells are a part of the immune system and can secrete inflammatory molecules, such as histamine, in response to allergens and other triggers. Generated in the bone marrow, mast cells play vital roles in acquired and innate immunity within tissues in the body. Little is known about their secretory process except that energy generated by mitochondria is required.

When a person contracts an infection or has an allergic reaction, mast cells normally secrete molecules that alert the immune system to the presence of a foreign invader. These molecules trigger the body’s responses in order to contain and eliminate the infection or alert the body to initiate an inflammatory response. After this process, the mast cell regenerates. The research team sought to understand how inflammation could be triggered without the presence of an infection or allergen.

In the study, mast cells were stimulated by triggers secreted from nerves, rather than by infection or allergen. As a result, the mast cells secreted their inflammation-causing molecules, as well as some mitochondrial components. The mitochondrial components were secreted outside the cell into the extracellular fluid, but the mast cells retained their viability, indicating that the secretion of mitochondrial particles was not due to cell damage or death. The extracellular mitochondrial components then stimulated other skin cells to mount an auto-inflammatory response.

Purified human mitochondrial components were also injected into peripheral tissue of rats. Within four hours, they were detected in the blood, which suggests that mitochondrial components secreted in tissues can reach the systemic circulation, the part of the cardiovascular system that carries blood from the heart to the rest of the body.

“The immune system misread the mitochondrial components as an infectious agent, and there was inflammation as a result,” said first author Bodi Zhang, MD, MPH, PhD, graduate of the biochemistry program at the Sacker School. “Our study findings are different from a report last year suggesting that mitochondrial particles are released from damaged cells in patients with severe trauma. Additional studies are needed to gain a better understanding of this process.”

“Our work provides a possible explanation for inflammation that arises without apparent disease or injury,” said senior author Theoharis C. Theoharides, MS, MD, PhD, professor of molecular physiology and pharmacology at Tufts University School of Medicine and member of the Biochemistry, and Pharmacology & Experimental Therapeutics graduate program faculties at the Sackler School. “Secretion of mitochondrial components by immune cells may constitute an ‘innate pathogen’ that may stimulate self-response by the immune system.”

“Although this study does not identify the inflammatory mechanism that is common among auto-inflammatory illnesses, the findings help to lay a foundation for further research and may lead to new biomarkers and novel treatment targets,” Theoharides added.

This research was supported in part by grants to Theoharides from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award number R01AR47652 and by Safe Minds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Tufts University has filed a patent application related to these findings.

Additional authors on the study are Shahrzad Asadi, PharmD, postdoctoral scholar in the Theoharides laboratory; Zuyi Weng, BS, graduate student in the Pharmacology & Experimental Therapeutics program at the Sackler School working in Dr. Theoharides’ laboratory; and Nikolaos Sismanopoulos, MD, formerly a postdoctoral fellow in the Theoharides’ laboratory and now at St. Elizabeth’s Medical Center. The authors have declared that no competing interests exist.

Zhang B, Asadi S, Weng Z, Sismanopoulos N, Theoharides TC. 2012. Stimulated human mast cells secrete mitochondrial components that have autocrine and paracrine inflammatory actions. PLoS ONE 7: e49767. Epub ahead of print.

Genetic Variant Linked to Decreased Heart Disease

Fri, 14 Dec 2012 00:00:00 -0500

BOSTON (December 14, 2012) – Scientists at the Jean Mayer USDA Human Nutrition Research Center on Aging (HNRCA) at Tufts University have discovered a new gene mechanism that appears to regulate triglyceride levels. This pathway may protect carriers of a gene variant against cardiovascular disease, especially among those with greater intakes of polyunsaturated fat (PUFA). The findings, published online this week in the American Journal of Human Genetics, contribute to research efforts to develop gene-specific diets that could potentially improve general health and complement chronic disease prevention and treatment.

The authors analyzed data from more than 27,000 men and women enrolled in ten epidemiological studies conducted in the United States and Europe that comprise the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Focusing on the Single Nucleotide Polymorphism (SNP) rs13702, they observed that a type of small RNA known as microRNA (miR), impacts production of lipoprotein lipase (LPL), an enzyme that mediates the metabolism of circulating triglycerides.

“We saw no miR activity in carriers of the gene variant,” said senior author José M. Ordovás, senior scientist and director of the Nutritional Genomics Laboratory at the HNRCA at Tufts University. “In the majority of the subjects the miR appeared to attach to the messenger RNA (mRNA), slowing down the manufacturing of LPL. Without that interference, people with the variant would presumably have more LPL available to breakdown excess triglycerides and prevent them from being deposited in the arteries, which could eventually lead to atherosclerosis and other cardiovascular diseases.”

The authors also noted lower triglyceride levels and higher concentrations of high-density lipoprotein (HDL) cholesterol, the so-called “healthy” cholesterol in association with the gene variant. Furthermore, carriers tended to have even lower triglyceride blood levels if they had higher PUFA intake.

“Based on the data, carriers of the gene variant may be able to further reduce their risk for cardiovascular disease by increasing their PUFA intake,” said Kris Richardson, Ph.D., a USDA Agricultural Research Service (ARS) post-doctoral associate in the Nutritional Genomics Laboratory and a recent graduate of Genetics PhD Program of the Sackler School of Graduate Biomedical Sciences at Tufts University. “To build on our observational data, future studies might investigate the effect of treating human cells in culture with PUFA to determine if it will mediate LPL levels through the identified miR.”

PUFA, found in foods such as salmon and vegetable oils, is considered a healthier fat. The current U.S. Dietary Guidelines for Americans recommend replacing saturated fats with the more beneficial PUFA and monounsaturated fats whenever possible.

José M. Ordovás is also a professor at the Friedman School of Nutrition Science and Policy at Tufts University and a member of the Genetics and Pharmacology & Experimental Therapeutics Graduate Faculty at the Sackler School.

This study is funded by grants from USDA and the National Heart, Lung and Blood Institute (NHLBI), award number P50 HL105185-01. A complete list of funding sources is available in the supplemental data portion of the paper.

Richardson, K, et al. 2013. Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site. Am J Hum Genet. Epub ahead of print.

New MS in Pharmacology and Drug Development - Applications Invited Until April 15, 2013

Wed, 21 Nov 2012 00:00:00 -0500

The Sackler School is pleased and excited to announce a new degree program leading to an MS degree in Pharmacology & Drug Development. Applications are now being accepted for September 2013 admission.

This new program responds to the growing need for trainees with advanced training in clinical pharmacology and drug development. Individuals already working in the pharmaceutical industry who wish to acquire new skills that will facilitate advancement or those interested in these careers will find that this program is ideally suited to their needs.

Some students who have completed their baccalaureate education abroad and seek to explore training opportunities in the United States may also find this program extremely attractive.

The two-year program combines strong course work and provides for laboratory research.

Learn more about this exciting new program

Garlick Featured in TLR Innovations

Tue, 20 Nov 2012 00:00:00 -0500

Soto and Sonenshein Honored with Gabbay Award

Mon, 22 Oct 2012 00:00:00 -0400

Sackler and Tufts to Say Goodbye to Peggy Newell

Wed, 26 Sep 2012 09:53:00 -0400

Peggy Newell, Vice Provost of Tufts University, has accepted the position of Deputy Provost at Harvard University and will leave Tufts on November 1.

Peggy started her career at Tufts as the Sackler School Registrar in 1982 and later was our Assistant and then Associate Dean before moving on to serve the university in several leadership positions.

Student Research Featured on Mechanisms of Development Cover

Thu, 20 Sep 2012 00:00:00 -0400

Many journals select cover art from papers that appear in each issue. Recently, cover art illustrating work conducted by Steven DelSignore, a CMDB student in Victor Hatini's lab was chosen for this honor by Mechanisms of Development. A figure from DelSignore, et al (Del Signore SJ, Hayashi T, Hatini V.2012. odd-skipped genes and lines organize the notum anterior-posterior axis using autonomous and non-autonomous mechanisms. Mech Dev. 129: 147-161) was selected as the cover illustration for the issue of the journal.

Learn more about Steven's work

See the cover art

Soto Quoted in Boston Herald

Wed, 19 Sep 2012 00:00:00 -0400

Dean Rosenberg Selected as Chair Elect of GREAT Group

Fri, 14 Sep 2012 00:00:00 -0400

Dean Naomi Rosenberg has been selected as the Chair Elect of the AAMC Graduate Research Education and Training group, the AAMC organization supports development and fosters innovation in PhD, MD-PhD and postdoctoral training.

Weinstock Comments on Whipworms to Battle Crohn's Disease

Wed, 05 Sep 2012 00:00:00 -0400

CTS Faculty Member Johanna Seddon Recognized by National Foundation Against Blindness

Thu, 30 Aug 2012 19:30:00 -0400

Jaffe Study in Nature Medicine Highlighted

Mon, 27 Aug 2012 00:00:00 -0400

Weinstock comments on parasites and autoimmunity

Mon, 27 Aug 2012 00:00:00 -0400

Feig Research Highlighted

Fri, 24 Aug 2012 11:29:00 -0400

Sackler Investigators Shed Light on Origins of Anxiety

Wed, 22 Aug 2012 15:11:00 -0400

BOSTON (August 22, 2012) — A study in mice conducted by researchers at Tufts University School of Medicine suggests that a woman’s risk of anxiety and dysfunctional social behavior may depend on the experiences of her parents, particularly fathers, when they were young. The study, published online in Biological Psychiatry, suggests that stress caused by chronic social instability during youth contributes to epigenetic changes in sperm cells that can lead to psychiatric disorders in female offspring across multiple generations.

“The long-term effects of stress can be pernicious. We first found that adolescent mice exposed to chronic social instability, where the cage composition of mice is constantly changing, exhibited anxious behavior and poor social interactions through adulthood. These changes were especially prominent in female mice,” said first author Lorena Saavedra-Rodríguez, PhD, postdoctoral fellow in the Larry Feig laboratory at Tufts University School of Medicine.

The researchers then studied the offspring of these previously-stressed mice and observed that again female, but not male, offspring exhibited elevated anxiety and poor social interactions. Notably, even though the stressed males did not express any of these altered behaviors, they passed on these behaviors to their female offspring after being mated to non-stressed females. Moreover, the male offspring passed on these behaviors to yet another generation of female offspring.

“We are presently searching for biochemical changes in the sperm of stressed fathers that could account for this newly appreciated form of inheritance” said senior author Larry A. Feig, PhD, professor of biochemistry at Tufts University School of Medicine and member of the biochemistry and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts University. “Hopefully, this work will stimulate efforts to determine whether similar phenomena occur in humans.”

This research was supported by award numbers AA019317 from the National Institute on Alcohol Abuse and Alcoholism, and MH083324 from the National Institute of Mental Health, both part of the National Institutes of Health (NIH). The research was also supported by award number NS047243 from National Institute of Neurological Disorders and Stroke (NIH) to the Tufts Center for Neuroscience Research.

Saavedra-Rodríguez L, Feig LA. 2012. Chronic social instability induces anxiety and defective social interactions across generations. Biol Psych. Epub ahead of print.

###

Killer Bacteria Licked at NIH

Wed, 22 Aug 2012 00:00:00 -0400

Sackler Family Cancer Award Recipients Announced

Thu, 09 Aug 2012 07:35:00 -0400

The recipients of the 2012-2013 Sackler Families Collaborative Cancer Biology Awards have been selected.These awards support a student stipend and provide monies to supplement research costs for one year. These awards are designed to provide support for innovative studies in cancer biology that will advance our knowledge of this disease and have the potential for translation and an eventual impact on patient care.

This year's recipients are Adam Skibinski, CMDB and MD-PhD student and Charlotte Kuperwasser, for their project ““The Role of the Transcriptional Co-activator TAZ in Mammary Gland Lineage Commitment and Breast Cancer” PhD, Advisor and Andrew Reeves, CMDB student and David Kaplan, PhD, Advisor for their project ““Regulation of Sox9 in Human Hair Follicle Stem Cells and the Implications for Sox9 Regulation in Basal Cell Carcinoma”.

Kaplan and Reeves

David Kaplan, PhD and his Cell, Molecular and Developmental Biology student Andrew Reeves received a Sackler Family Collaborative Cancer Biology Research Award this year for their application “Regulation of Sox9 in Human Hair Follicle Stem Cells and the Implications for Sox9 Regulation in Basal Cell Carcinoma”. Basal cell carcinoma and other non-melanoma skin cancers are the most common forms of cancer world-wide. Although these diseases have a low mortality, the cost of treatment places them among the top five cancers in terms of health care expenditures. These tumors arise in the stem cell compartment of the hair follicle but the ways in which growth signaling is altered in these cells and leads to tumor development is poorly understood. Kaplan and Reeves are testing the idea that regulation of Sox9, a transcription factor expressed in the stem cells plays a key role in the process. They are particularly focused on the ways Wnt and Notch pathway components influence Sox9 function. Unraveling the circuits by which Sox9 and Wnt and Notch regulate these stem cells will contribute to a better understanding of how these tumors arise and may, in the long run, suggest more effective therapeutic targets.

Kuperwasser and Skibinski

Charlotte Kuperwasser, PhD and her Cell, Molecular and Developmental Biology and MD-PhD student Adam Skibinski received a Sackler Family Collaborative Cancer Biology Research Award this year for their application “The Role of the Transcriptional Co-activator TAZ in Mammary Gland Lineage Commitment and Breast Cancer”. Breast cancer is the most common cancer affecting women and women who develop basal-like or triple-negative breast cancers fail to respond to hormone-based therapies and usually have a poor prognosis. To understand the molecular events that are important in this type of breast cancer, Skibinski used a functional transcription factor screen and identified TAZ as a potential regulator of the basal lineage compartment in the breast and has developed data supporting this idea. Kuperwasser and Skibinski now plan to probe the role of TAZ more fully using a loss-of-function mouse model and also determine how TAZ maintains basal cell differentiation state. Their findings could lead to a clearer understanding of the molecular mechanisms that control development of basal-like breast cancer, an advance that could eventually lead to better approaches to treatment for a type of breast cancer for which no targeted therapies are currently available.

Leon Reijmers Honored as 2012 Sackler Faculty Mentor

Wed, 08 Aug 2012 07:39:00 -0400

Leon Reijmers, PhD, a member of the graduate program in Neuroscience and Assistant Professor of Neuroscience at TUSM has been selected as this year's recipient of the Sackler Faculty Outstanding Mentor Award. Dr. Reijmers was nominated by students from the Neuroscience PhD program who cited his strong commitment to students, his ability to be supportive while setting high standards for scientific achievement.

Learn more about the Sackler Faculty Mentor Award

Sackler Faculty Contribute to TUSM High School Students and Teachers Program

Tue, 07 Aug 2012 19:54:00 -0400

BOSTON (August 3, 2012) - Tufts University School of Medicine today celebrated the achievements of the 33 Massachusetts high school students who participated in the School’s 2012 Teachers and High School Student Program. The program is one of Tufts’ signature initiatives to encourage high school students with diverse backgrounds to explore their interest in medicine and biomedical sciences. Established in 1989, the Tufts program supports the careers of aspiring young doctors and scientists by engaging them in a range of clinical and research opportunities across the Tufts Health Sciences campus in Boston.

“Tufts University is committed to nurturing scientific curiosity among young people of diverse backgrounds, particularly those from communities that are underrepresented in medicine and the health sciences,” said Harris Berman, M.D., dean of Tufts University School of Medicine. “The extraordinary students who participated in our high school program this summer have contributed immeasurably to the Tufts community, and we are proud to offer high school students the opportunity to launch promising careers as health professionals.”

“Our summer program for high school students offers invaluable experience to young people who might not otherwise have opportunities to explore their budding interests in medicine and the biomedical sciences,” said Joyce Sackey, M.D., dean for multicultural affairs and global health and associate professor at Tufts University School of Medicine. “Tufts’ Teachers and High School Students Program is one of our key initiatives to support the educational development of youth in our community.”

Selected high school students participated in a seven-week program and spent up to 25 hours each week in various positions at Tufts University School of Medicine, Tufts University School of Dental Medicine, Sackler Graduate School of Biomedical Sciences at Tufts or Tufts Medical Center. Students also took a gross anatomy course taught by Tufts medical students and gained knowledge of laboratory-based science; in the process, students developed relationships with medical and graduate student mentors that Tufts expects will continue beyond the summer program.

The Tufts program also includes an independent study, the findings of which the students presented to the Tufts community, family and friends today. Participating students and their projects were:

Edward Akubude (Mattapan), 16, Concord-Carlisle Regional High School “Reduction of OCD Symptoms in Mice”
Carlos Angeles (Norton), 19, Xaverian Brothers High School “The Relationship Between Diabetes and Diet”
Christina Augustin (Medford), 16, Prospect Hill Academy Charter School “The Effects of Marijuana on Pregnancy”
Janika Beatty (Malden), 17, Community Charter School of Cambridge “The Effects of Marijuana on Pregnancy”
Carrington Cazeau (Boston), 16, Natick High School “Zebrafish Fin Mutations”
Walter Chacon (Lynn), 16, Phillips Academy Andover “The Relationship Between Obesity and Depression”
Malka Forman (Brighton), 17, Maimonides School “Lower Limb Ischemic Threshold with Near Infrared Spectrometry Device”
John Frazer (Quincy), 16, Boston College High School “Evidence Based Review of Domestic Violence” (The reporting and recognition by healthcare providers of child abuse and neglect in the Latino population)”
Ericka Garcia (Brookline) 15, Brookline High School “Leukemia in Children”
Bryant Gill (Foxboro), 17, Xaverian Brothers High School “Correlation of Neuronal Signal to Astrocyte Morphology”
Nathan Gill (Foxboro), 16, Xaverian Brothers High School “Reduction of OCD symptoms in Mice”
Yvonne Hamisi (Springfield), 18, Baystate-Springfield Educational Partnership “Cardiac Differences Between Athletes and Non-Athletes”
Elyane James (Dorchester), 18, Marblehead High School “Evidence Based Review of Domestic Violence” (The reporting and recognition by healthcare providers of child abuse and neglect in the Latino population)”
Hyunji Koo (North Andover), 16, Phillips Academy Andover “Cross-cultural Communication and the Doctor-Patient Relationship”
Fatima Khan (Somerville), 16, Prospect Hill Academy Charter School “Abdominal Aortic Aneurysms”
Ryan Kuehl (Springfield), 18, Baystate-Springfield Educational Partnership “Too Much Exercise?”
Anthony “Nino” Lambert (Hanover), 16, Boston College High School “Factors That Affect the Concentration of Serine”
Jessica Mar (Brighton), 16, Boston Latin School “Physician Wellness”
Abby Mendez (Roxbury), 17, City on a Hill “Evidence Based Review of Domestic Violence (The reporting and recognition by healthcare providers of child abuse and neglect in the Latino population)”
Jasmine Ngan (Somerville), 16, Prospect Hill Academy Charter School “The Effects of Storage Conditions on Bloodspot Amino Acids”
Blessing Ojini (Roxbury), 16, Needham High School “The Benefits of Play in Child Development”
Emanuel Parrilla (Springfield), 18, Baystate-Springfield Educational Partnership “The Effects of a Torn ACL in Later Life”
Klarissa Ramkissoon (Milton), 17, Milton High School “Behavioral Testing in Mice”
Krystina San Soucie (Upton), 16, Nipmuc Regional High School “Methods to Maximize Serine Levels”
Abdullahi Tahlil (Roxbury), 17, Match High School “Child Health Assessment Mapping Project”
Lisa Tam (Boston), 18, John D. O'Bryant High School of Math and Science “Effectiveness of Home Visits Compared with Standard Care”
Dorothy Tran (Boston), 17, The Winsor School “Child Health Assessment Mapping Project”
Arianna Unger (Newton), 17, Maimonides School “A Comparative Study of Two Orthotic Systems Used for the Assisted Ambulation of a Child with Spina Bifida”
Camille Van Allen (Milton), 17, Milton High School “Benefits of Breast Feeding”
Winnie Wang (Boston), 18, Boston Latin School “Relationship Between Toxic/Nutritional and Leber's Hereditary Optic Neuropathy”
Natalie Wolanski (Springfield), 17, Baystate-Springfield Educational Partnership “Concussions in Sports and Society”
Davonte Willis (Quincy), 18, Quincy High School “Factors That Affect the Concentration of Amine Acids”
Kavin Zhu (Boston), 17, Boston Latin School “Genetic Disease as Exemplified by Hunter Syndrome”

The Teachers and High School Students Program is one of a number of “pipeline” programs at Tufts University School of Medicine designed to engage diverse students interested in the fields of medicine and biomedical sciences. Tufts offers programs for diverse students in middle school, high school, and college, as well as college graduates.

# # #

If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at Tufts University, please contact Jennifer Kritz at 617-636-3707 or Siobhan Gallagher at (617) 636-6586.

Sackler Faculty Honored with Zucker Research Prizes

Tue, 07 Aug 2012 00:00:00 -0400

Two Sackler School faculty members are the 2012 recipients of the Zucker Research prizes. These awards recognize outstanding achievement in research. The recipient of the Zucker Family Prize is Harry Selker, MD, Professor of Medicine and member of the Clinical & Translational Science Program. The recipient of the Milton O and Natalie V Zucker Prize is Thereza Imanishi-Kari, PhD, Associate Professor of Pathology and member of the Genetics and Immunology Programs.

Dr. Selker was recognized for his outstanding contributions in the development of treatment strategies, decision aids, methods and systems that improve emergency and cardiac care. His development and testing of electrocardiograph-based predictive instruments have had a lasting world-wide impact. His leadership of the IMMEDIATE trial is particularly noteworthy. The results of this study have changed the way paramedics provide emergency treatment to cardiac patients and should reduce mortality. Indeed, this work demonstrates the need for well-conceived and controlled clinical trials that allow assessment of particular interventions and treatments.

Dr. Imanishi-Kari was recognized for her research on basic mechanisms of auto-immunity and the development of antibody-producing B lymphocytes. Her research, which has always focused on understanding the pathogenesis of systemic lupus erythematosus, has changed our understanding of the mechanisms by which this disease arises. Among the seminal findings are the identification of a novel and unanticipated mechanism of antibody gene diversification in developing B cells that can lead to the development of auto-immunity. Dr. Imanishi-Kari's group also was among the first to appreciate the role of the innate immune response in auto-immune disorders.

Neuroscience Triumphs at the Sackler Relays

Fri, 03 Aug 2012 00:00:00 -0400

Team Neuroscience won the Sackler Relays this year with strong showings in multiple events. Team CMDB and Team Immunology battled to a second place tie.

Despite one of the hottest days in relay history, everyone had a great time. Congratulations to the GSC for organizing a wonderful event.

Check out the slide show

See the new T-shirts

Kaplan Group Develops Silk based Vaccine Stabilizer

Thu, 02 Aug 2012 12:38:00 -0400

Possible Intervention for Breast Cancer Developed by Sackler Faculty

Wed, 01 Aug 2012 00:00:00 -0400

Globe Article Highlights Tesco Research

Mon, 30 Jul 2012 19:21:00 -0400

Congratulations to the 2012-2013 Dean's Fellows

Fri, 27 Jul 2012 12:14:00 -0400

Congratulations to the students selected as 2012-2013 Dean’s Fellows. Dean’s Fellows are selected from the rising third year PhD students and are awarded a school-supported stipend for the year based on high achievement in scholarship and research at Sackler. They also receive a monetary prize at the end of their year as Dean’s Fellows.

This year’s recipients are:

Seblewongel Asrat, Molecular Microbiology
Neeru Bhardwaj, Molecular Microbiology
Benjamin Dake, CMDB
Benjamin Umiker, Immunology

Learn more about this year's award recipients.

Sackler Team Probes Effect of Traumatic Brain Injury

Tue, 24 Jul 2012 17:40:00 -0400

BOSTON (July 24, 2012, 5:00PM EST) — A study, performed in mice and utilizing post-mortem samples of brains from patients with Alzheimer’s disease, found that a single event of a moderate-to-severe traumatic brain injury (TBI) can disrupt proteins that regulate an enzyme associated with Alzheimer’s. The paper, published in The Journal of Neuroscience, identifies the complex mechanisms that result in a rapid and robust post-injury elevation of the enzyme, BACE1, in the brain. These results may lead to the development of a drug treatment that targets this mechanism to slow the progression of Alzheimer’s disease.

“A moderate-to-severe TBI, or head trauma, is one of the strongest environmental risk factors for Alzheimer’s disease. A serious TBI can lead to a dysfunction in the regulation of the enzyme BACE1. Elevations of this enzyme cause elevated levels of amyloid-beta, the key component of brain plaques associated with senility and Alzheimer’s disease,” said first author Kendall Walker, PhD, postdoctoral associate in the department of neuroscience at Tufts University School of Medicine (TUSM).

Building on her previous work, neuroscientist Giuseppina Tesco, MD, PhD, of Tufts University School of Medicine (TUSM), led a research team that first used an in vivo model to determine how a single episode of TBI could alter the brain. In the acute phase (first two days) following injury, levels of two intracellular trafficking proteins (GGA1 and GGA3) were reduced, and an elevation of BACE1 enzyme level was observed.

Next, in an analysis of post-mortem brain samples from patients with Alzheimer’s disease, the researchers found that GGA1 and GGA3 levels were reduced while BACE1 levels were elevated in the brains of Alzheimer’s disease patients compared to the brains of people without Alzheimer’s disease, suggesting a possible inverse association.

In an additional experiment using a mouse strain genetically modified to express the reduced level of GGA3 that was observed in the brains of Alzheimer’s disease patients, the team found that one week following traumatic brain injury, BACE1 and amyloid-beta levels remained elevated even when GGA1 levels had returned to normal. The research suggests that reduced levels of GGA3 were solely responsible for the increase in BACE 1 levels and therefore the sustained amyloid-beta production observed in the sub-acute phase, or seven days, after injury.

“When the proteins are at normal levels, they work as a clean-up crew for the brain by regulating the removal of BACE1 enzymes and facilitating their transport to lysosomes within brain cells, an area of the cell that breaks down and removes excess cellular material. BACE1 enzyme levels may be stabilized when levels of the two proteins are low, likely caused by an interruption in the natural disposal process of the enzyme,” said Tesco, assistant professor of neuroscience at Tufts School of Medicine and member of the neuroscience program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

“We found that GGA1 and GGA3 act synergistically to regulate BACE1 post-injury. The identification of this interaction may provide a drug target to therapeutically regulate the BACE1 enzyme and reduce the deposition of amyloid-beta in Alzheimer’s patients,” she continued. “Our next steps are to confirm these findings in post-mortem brain samples from patients with moderate-to-severe traumatic brain injuries.”

Moderate-to-severe TBIs are caused most often by traumas, such as severe falls or motor vehicle accidents, that result in a loss of consciousness. Not all traumas to the head result in a TBI. According to the Centers for Disease Control and Prevention, each year 1.7 million people sustain a TBI. Concussions, the mildest form of a TBI, account for about 75% of all TBIs. Studies have linked repeated head trauma to brain disease and some previous studies have linked single events of brain trauma to brain disease, such as Alzheimer’s. Alzheimer’s disease currently affects as many as 5.1 million Americans and is the most common cause of dementia in adults age 65 and over.

Additional authors on the study are Eugene Kang, MPH, research assistant in the department of neuroscience at TUSM; Michael Whalen, MD, PhD, Neuroscience Center and department of pediatrics at Massachusetts General Hospital and associate professor at Harvard Medical School; and Yong Shen, MD, PhD, of the Center for Advanced Therapeutic Strategies for Brain Disorders at Roskamp Institute.

This study was supported by grants from the National Institute on Aging (R01AG033016 and R01AG025952), part of the National Institutes of Health; and a grant from the Cure Alzheimer’s Fund.

Walker KR, Kang EL, Whalen MJ, Shen Y, Tesco G. 2012. Depletion of GGA1 and GGA3 mediates post-injury elevation of BACE1. J Neurosci. Epub ahead of print.

###

If you are a member of the media interested in learning more about this topic or speaking with a faculty member at the Tufts University School of Medicine or another Tufts health sciences researcher, please contact Jennifer Kritz at 617-636-3707.

Sackler Team Gains Insight on Candida Pathogenesis

Tue, 24 Jul 2012 00:00:00 -0400

BOSTON (July 24, 2012) - The opportunistic fungal pathogen Candida albicans inconspicuously lives in our bodies until it senses that we are weak, when it quickly adapts to go on the offensive. The fungus, known for causing yeast and other minor infections, also causes a sometimes-fatal infection known as candidemia in immunocompromised patients. An in vivo study, published in mBio, demonstrates how C. albicans can distinguish between a healthy and an unhealthy host and alter its physiology to attack.

“The ability of the fungus to sense the immune status of its host may be key to its ability to colonize harmlessly in some people but become a deadly pathogen in others,” said Jessica V. Pierce, BA, PhD student in the molecular microbiology program at the Sackler School of Graduate Biomedical Sciences at Tufts.

“Effective detection and treatment of disease in immunocompromised patients could potentially work by targeting the levels of a protein, Efg1p, that we found influenced the growth of Candida albicans inside the host,” she continued.

The researchers knew from previous research that Efg1p influences the expression of genes that regulate how harmful a fungal cell can become. Surprisingly, the investigators found that lower Efg1p levels allow the fungal cells to grow to high levels inside a host. Higher levels of the protein result in less growth.

To examine how the immune status could affect the growth of C. albicans within a host, the researchers fed both healthy and immunocompromised mice equal amounts of two fungal strains containing two different levels of the Efg1p protein.

Fecal pellets from the mice were tested to determine which strain of fungi thrived. In a healthy host, the fungal cells with higher levels of the protein predominated.

In immunocompromised mice, the fungal cells with lower levels of the protein flourished. The researchers noted that lack of interactions with immune cells in the intestinal tract most likely caused the necessary environmental conditions favoring fungal cells that express lower levels of the protein, resulting in fungal overgrowth and setting the stage for systemic infection.

“By having a mixed population with some high Efg1p cells and some low Efg1p cells, the fungus can adjust its physiology to remain benign or become harmful when it colonizes hosts with varying immune statuses. These findings are important because they provide the first steps toward developing more effective methods for detecting and treating serious and stubborn infections caused by Candida albicans, such as candidemia,” said Carol A. Kumamoto, PhD, professor of molecular biology and microbiology at Tufts University School of Medicine and member of the molecular microbiology and genetics program faculties at the Sackler School of Graduate Biomedical Sciences.

The immune system and “good bacteria” within the body act to regulate the size of C. albicans fungal populations in healthy individuals. When the immune system is compromised, the fungus can spread throughout the body. Candidemia, i.e. blood-borne Candida, is the fourth most common blood infection among hospitalized patients in the United States and is found in immunocompromised patients such as babies, those with catheters, and the critically ill.

mBio is an online-only, open access journal published in association with the American Society for Microbiology.

This research was supported in part by grants AI076156, AI08179, and AI07422 from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Pierce JV, Kumamoto CA. 2012. Variation in Candida albicans EFG1 expression enables host-dependent changes in colonizing fungal populations mBio 3: e00117-12.

###

If you are a member of the media interested in learning more about this topic, or speaking with a faculty member at the Tufts University School of Medicine, the Sackler School or another Tufts health sciences researcher, please contact Jennifer Kritz at 617-636-3707.