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  • richardmitnick 10:09 pm on December 25, 2016 Permalink | Reply
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    From Rockefeller: “Researchers develop automated melanoma detector for skin cancer screening” 

    Rockefeller U bloc

    Rockefeller University

    December 23, 2016
    No writer credit

    1
    Malignant or benign?: An image of a skin lesion is processed by a new technology to extract quantitative data, such as irregularities in the shape of pigmented skin, which could help doctors determine if the growth is cancerous.

    Even experts can be fooled by melanoma. People with this type of skin cancer often have mole-looking growths on their skin that tend to be irregular in shape and color, and can be hard to tell apart from benign ones, making the disease difficult to diagnose.

    Now, researchers at The Rockefeller University have developed an automated technology that combines imaging with digital analysis and machine learning to help physicians detect melanoma at its early stages.

    “There is a real need for standardization across the field of dermatology in how melanomas are evaluated,” says James Krueger, D. Martin Carter Professor in Clinical Investigation and head of the Laboratory of Investigative Dermatology. “Detection through screening saves lives but is very challenging visually, and even when a suspicious lesion is extracted and biopsied, it is confirmed to be melanoma in only about 10 percent of cases.”

    In the new approach, images of lesions are processed by a series of computer programs that extract information about the number of colors present in a growth, and other quantitative data. The analysis generates an overall risk score, called a Q-score, which indicates the likelihood that the growth is cancerous.

    Published in Experimental Dermatology, a recent study evaluating the tool’s usefulness indicates that the Q-score yields 98 percent sensitivity, meaning it is very likely to correctly identify early melanomas on the skin. The ability of the test to correctly diagnose normal moles was 36 percent, approaching the levels achieved by expert dermatologists performing visual examinations of suspect moles under the microscope.

    “The success of the Q-score in predicting melanoma is a marked improvement over competing technologies,” says Daniel Gareau, first author of the report and instructor in clinical investigation in the Krueger laboratory.

    The researchers developed this tool by feeding 60 photos of cancerous melanomas and an equivalent batch of pictures of benign growths into image processing programs. They developed imaging biomarkers to precisely quantify visual features of the growths. Using computational methods, they generated a set of quantitative metrics that differed between the two groups of images—essentially identifying what visual aspects of the lesion mattered most in terms of malignancy—and gave each biomarker a malignancy rating.

    By combining the data from each biomarker, they calculated the overall Q-score for each image, a value between zero and one in which a higher number indicates a higher probability of a lesion being a cancerous.

    As previous studies have shown, the number of colors in a lesion turned out to be the most significant biomarker for determining malignancy. And some biomarkers were significant only if looked at in specific color channels—a finding the researchers say could potentially be exploited to identify additional biomarkers and further improve accuracy.

    “I think this technology could help detect the disease earlier, which could save lives, and avoid unnecessary biopsies too,” says Gareau. “Our next steps are to evaluate this method in larger studies, and take a closer look at how we can use specific color wavelengths to reveal aspects of the lesions that may be invisible to the human eye, but could still be useful in diagnosis.”

    This work was supported in part by the National Institutes of Health and in part by the Paul and Irma Milstein Family Foundation and the American Skin Association.

    See the full article here .

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 12:01 pm on August 18, 2016 Permalink | Reply
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    From Rockefeller: “Zika infection may affect adult brain cells, suggesting risk may not be limited to pregnant women” 

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    Rockefeller University

    August 18, 2016
    No clear writer credit

    1
    Zika in the adult brain: Illumination of the fluorescent biomarker in green revealed that Zika can infect the adult mouse brain in a region full of neural progenitor cells, which play an important role in learning and memory.

    Concerns over the Zika virus have focused on pregnant women due to mounting evidence that it causes brain abnormalities in developing fetuses. However, new research in mice from scientists at The Rockefeller University and La Jolla Institute for Allergy and Immunology suggests that certain adult brain cells may be vulnerable to infection as well. Among these are populations of cells that serve to replace lost or damaged neurons throughout adulthood, and are also thought to be critical to learning and memory.

    “This is the first study looking at the effect of Zika infection on the adult brain,” says Joseph Gleeson, adjunct professor at Rockefeller, head of the Laboratory of Pediatric Brain Disease, and Howard Hughes Medical Institute investigator. “Based on our findings, getting infected with Zika as an adult may not be as innocuous as people think.”

    Although more research is needed to determine if this damage has long-term biological implications or the potential to affect behavior, the findings suggest the possibility that the Zika virus, which has become widespread in Central and South America over the past eight months, may be more harmful than previously believed. The new findings were published in Cell Stem Cell on August 18.

    “Zika can clearly enter the brain of adults and can wreak havoc,” says Sujan Shresta, a professor at the La Jolla Institute of Allergy and Immunology. “But it’s a complex disease—it’s catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle, and now we know what to look for.”

    Neuronal progenitors

    Early in gestation, before our brains have developed into a complex organ with specialized zones, they are comprised entirely of neural progenitor cells. With the capability to replenish the brain’s neurons throughout its lifetime, these are the stem cells of the brain. In healthy individuals, neural progenitor cells eventually become fully formed neurons, and it is thought that at some point along this progression they become resistant to Zika, explaining why adults appear less susceptible to the disease.

    But current evidence suggests that Zika targets neural progenitor cells, leading to loss of these cells and to reduced brain volume. This closely mirrors what is seen in microcephaly, a developmental condition linked to Zika infection in developing fetuses that results in a smaller-than-normal head and a wide variety of developmental disabilities.

    The mature brain retains niches of these neural progenitor cells that appear to be especially impacted by Zika. These niches—in mice they exist primarily in two regions, the subventricular zone of the anterior forebrain and the subgranular zone of the hippocampus—are vital for learning and memory.

    Gleeson and his colleagues suspected that if Zika can infect fetal neural progenitor cells, it wouldn’t be a far stretch for them to also be able to infect these cells in adults. In a mouse model engineered by Shresta and her team to mimic Zika infection in humans, fluorescent biomarkers illuminated to reveal that adult neural progenitor cells could indeed be hijacked by the virus.

    “Our results are pretty dramatic—in the parts of the brain that lit up, it was like a Christmas tree,” says Gleeson. “It was very clear that the virus wasn’t affecting the whole brain evenly, like people are seeing in the fetus. In the adult, it’s only these two populations that are very specific to the stem cells that are affected by virus. These cells are special, and somehow very susceptible to the infection.”

    Beyond fetal brain infection

    The researchers found that infection correlated with evidence of cell death and reduced generation of new neurons in these regions. Integration of new neurons into learning and memory circuits is crucial for neuroplasticity, which allows the brain to change over time. Deficits in this process are associated with cognitive decline and neuropathological conditions, such as depression and Alzheimer’s disease.

    Gleeson and colleagues recognize that healthy humans may be able to mount an effective immune response and prevent the virus from attacking. However, they suggest that some people, such as those with weakened immune systems, may be vulnerable to the virus in a way that has not yet been recognized.

    “In more subtle cases, the virus could theoretically impact long-term memory or risk of depression,” says Gleeson, “but tools do not exist to test the long-term effects of Zika on adult stem cell populations.”

    In addition to microcephaly, Zika has been linked to Guillain-Barré syndrome, a rare condition in which the immune system attacks parts of the nervous system, leading to muscle weakness or even paralysis. “The connection has been hard to trace since Guillain-Barré usually develops after the infection has cleared,” says Shresta. “We propose that infection of adult neural progenitor cells could be the mechanism behind this.”

    There are still many unanswered questions, including exactly how translatable findings in this mouse model are to humans. Gleeson’s findings in particular raise questions such as: Does the damage inflicted on progenitor cells by the virus have lasting biological consequences, and can this in turn affect learning and memory? Or, do these cells have the capability to recover? Nonetheless, these findings raise the possibility that Zika is not simply a transient infection in adult humans, and that exposure in the adult brain could have long-term effects.

    “The virus seems to be traveling quite a bit as people move around the world,” says Gleeson. “Given this study, I think the public health enterprise should consider monitoring for Zika infections in all groups, not just pregnant women.”

    Joseph Gleeson also holds appointments at the University of California San Diego School of Medicine and Rady Children’s Hospital-San Diego. This research was supported by NIH grants R01NS041537, R01NS048453, R01NS052455, P01HD070494, and P30NS047101; the Simons Foundation Autism Research Initiative (SFARI); the Howard Hughes Medical Institute; California Institute of Regenerative Medicine (to J.G. Gleeson); NIH grant R01 AI116813 (to S. Shresta); and a Druckenmiller Fellowship from New York Stem Cell Foundation (to H. Li).

    See the full article here .

    YOU CAN HELP FIND A CURE FOR THE ZIKA VIRUS.

    There is a new project at World Community Grid [WCG] called OpenZika.
    Zika
    Zika depiction. Image copyright John Liebler, http://www.ArtoftheCell.com
    Rutgers Open Zika

    WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the OpenZika project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

    This project is directed by Dr. Alexander Perryman a senior researcher in the Freundlich lab, with extensive training in developing and applying computational methods in drug discovery and in the biochemical mechanisms of multi-drug-resistance in infectious diseases. He is a member of the Center for Emerging & Re-emerging Pathogens, in the Department of Pharmacology, Physiology, and Neuroscience, at the Rutgers University, New Jersey Medical School. Previously, he was a Research Associate in Prof. Arthur J. Olson’s lab at The Scripps Research Institute (TSRI), where he ran the day-to-day operations of the FightAIDS@Home project, the largest computational drug discovery project devoted to HIV/AIDS, which also runs on WCG. While in the Olson lab, he also designed, led, and ran the largest computational drug discovery project ever performed against malaria, the GO Fight Against Malaria project, also on WCG.

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    Please help promote STEM in your local schools.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 10:04 am on August 14, 2016 Permalink | Reply
    Tags: , , , Potassium channels, Rockefeller University   

    From Rockefeller: “Structural images shed new light on a cancer-linked potassium channel” 

    Rockefeller U bloc

    Rockefeller University

    August 11, 2016

    1

    Most cells in the body carry on their surface tiny pores through which potassium ions travel. In controlling the flow of these positively charged ions, the channel helps the cell maintain its electrical balance.

    One particular type of potassium channel, called Eag1, has been found in a number of cell types: in the neurons of the brain, in embryonic cells that generate muscle fiber, and in some tumor cells, where it’s thought to have a cancer-promoting effect. But it’s not yet clear how Eag1 differs from other potassium channels, or exactly how it works.

    A duo of researchers at The Rockefeller University has taken an early step toward an answer. Using Rockefeller’s new facility for cryo-electron microscopy, an advanced imaging technique in which samples are frozen then bombarded with electrons, they determined the structure of Eag1. Their results, which appear August 11 in Science, have provided the first 3-D structure of a molecule to be published from Rockefeller’s facility.

    2
    New views: Samples of the channel were frozen, then bombarded with electrons to produce the raw images shown above. This work was done in Rockefeller’s new cryo-electron microscopy facility.

    Like some other potassium channels, Eag1 opens when it senses a change in electrical potential, as happens when neurons send signals. In the video above, the part of the channel that most interested the researchers—the section that spans the cell membrane—appears in yellow and green.

    It includes the sensors responsible for detecting electrical changes (yellow), and the segments that form the pore through which potassium passes (green). The rest of the channel is located inside the cell. The researchers also determined the structure of another molecule called calmodulin (purple), which binds to Eag1 and holds it in a closed position.

    “Within the structure, we see some important differences between Eag1 and other potassium channels in the section that spans the cellular membrane,” says first author Jonathan Whicher, a postdoc in Roderick MacKinnon’s lab. “This gives us a better idea of how the channel’s components work on a molecular level, and its role within a cell, either a normal one or a cancerous one.”

    This research is an early step toward finding molecules that could inhibit or control the channel. These, in turn, could provide valuable tools for further exploring the role of Eag1 in cancer, or for developing new therapeutics.

    The study also begins to fill an important gap in understanding the function of potassium channels, which are the primary focus of MacKinnon’s Laboratory of Molecular Neurobiology and Biophysics. In 2003, MacKinnon, who is also the John D. Rockefeller Jr. Professor and a Howard Hughes Medical Institute investigator, won the Nobel Prize for capturing the 3-D structure of a potassium channel for the first time.

    This work was supported by the National Institutes of Health (grant GM43949) and the Damon Runyon Cancer Research Foundation (DRG-2212-15).

    See the full article here .

    Please help promote STEM in your local schools.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 4:35 pm on July 25, 2016 Permalink | Reply
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    From Rockefeller: ” New antibody drug continues to show promise for treatment of HIV” 

    Rockefeller U bloc

    Rockefeller University

    July 25, 2016
    Katherine Fenz
    kfenz@rockefeller.edu
    212-327-7913

    1
    Halting HIV: Antibody treatment delayed the virus (above) from rebounding in patients taken off their anti-retroviral medications.

    Great strides have been made in recent years to develop treatment options for HIV, and the disease can now be controlled with anti-retroviral drugs. But a cure remains elusive and current medications have limitations: they must be taken daily, for life, and can cause long-term complications.

    Now, Rockefeller scientists report that they are one step closer to an alternative treatment that utilizes antibodies. This therapy has the potential for long-acting effects and would allow for less frequent dosing.

    Recently published in Nature, the findings suggest that an antibody called 3BNC117 can effectively delay the virus from rebounding in patients who temporarily suspended their anti-retroviral medications, currently the standard treatment for HIV.

    “These are very positive results,” says Marina Caskey, Assistant Professor of Clinical Investigation in the Laboratory of Molecular Immunology, headed by Michel Nussenzweig. “This is the longest any antibody has been able to delay virus rebound.”

    Keeping HIV at bay

    The 3BNC117 antibody was isolated in the Nussenzweig lab several years ago by guest investigator Johannes Scheid, co-first author of this most recent publication. It was cloned from cells of an HIV-infected patient whose immune system was able to fight HIV particularly well. The virus primarily infects CD4 T cells, part of the immune system that helps protect the body from infection. 3BNC117 stops multiple strains of HIV from hijacking these cells.

    Anti-retroviral drugs suppress HIV by preventing its replication, but the virus remains dormant in the body, mostly in reservoirs within CD4 cells. If a patient stops taking anti-retroviral drugs, the virus is released from these reservoirs, and quickly rebounds.

    This small study, called a Phase IIa clinical trial, builds on a previous study from the Nussenzweig lab, in which HIV-infected patients were given the antibody without receiving other treatment. This time, the researchers tested 13 HIV-infected patients who had been treated successfully with antiviral therapy. The goal of the study was to determine whether the antibody alone would be able to maintain virus suppression in patients that were taken off anti-retroviral drugs.

    Caskey and colleagues found that the antibody was able to delay when the virus came back to about 10 weeks, compared to about 3 weeks in controls.

    Virus under pressure

    One of the many challenges in treating HIV is that the virus quickly mutates. As a result, patients carry many different strains that cannot be eliminated with a single medication, and each person’s virus repertoire is different. An advantage of 3BNC117 is that is has the ability to fight a wide range of HIV strains, but not all; some studies suggest it can neutralize about 80 percent of viral isolates taken from patients.

    In this study, the researchers tried to select participants whose viral strains were likely to be a good target for 3BNC117. However, current testing methods are not very precise in predicting exactly which strains are present, and patients had varied responses.

    “In one-third of participants, rebound happened very late, when the antibody levels were low,” says co-first author and former graduate student in the Nussenzweig lab, Josh Horwitz. “This means that the antibody was effective at suppressing the viruses that are sensitive to it, but it’s also clear that for the remaining patients with different strains of HIV, this antibody is not sufficient.”

    The researchers also found that the antibody was able to reduce the assortment of viral strains that rebounded, which tends to be very diverse in patients taken off antiretroviral medications. “We were excited to see a significant delay in rebound,” says Sheid, “but the reduced diversity of viruses that we saw is also promising because it will take fewer additional antibodies to target them.”

    The next step will be to test 3BNC117 in combination with another HIV-specific antibody, such as 10-1074, which targets the virus from a different angle, and has also been shown to decrease virus levels when given to HIV patients not on treatment.

    “There are a lot of factors at play here, part of which is that we are working with a diverse reservoir of viruses with different sensitivities to different antibodies,” says Caskey. “However, we are hopeful that testing the antibodies in combination will be successful in bringing us closer to better strategies to prevent and treat HIV.”

    This study was supported by the Collaboration for AIDS Vaccine Discovery, the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program, NIH Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Bill and Melinda Gates Foundation, the Robertson Foundation, the Ruth L. Kirschstein National Research Service Award, and other sources.

    See the full article here .

    YOU CAN HELP IN THE FIGHT AGAINST HIV/AIDS FROM THE COMFORT OF YOUR EASY CHAIR.

    The Fight AIDS at home (FAAH@home) Phase II project is now running at World Community Grid (WCG)

    FAAH Phase II

    WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the FAAH@home Phase II project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 2:15 pm on July 14, 2016 Permalink | Reply
    Tags: , , New approach exposes 3D structure of Alzheimer’s proteins within the brain, Rockefeller University   

    From Rockefeller: “New approach exposes 3D structure of Alzheimer’s proteins within the brain” 

    Rockefeller U bloc

    Rockefeller University

    July 14, 2016
    Katherine Fenz
    kfenz@rockefeller.edu
    212-327-7913

    1
    Above, amyloid-beta plaques appear as speckles within half of a brain of a mouse used to study the disease. Brain regions are coded by color, with the cerebellum in yellow, hippocampus in blue, thalamus in purple, striatum in red, and cortex in green.

    Alzheimer’s disease clouds memory, dims the mind, and distorts behavior. Its ravages also show up within the physical structure of the brain, perhaps most prominently as sticky clumps of a naturally occurring but harmful protein called amyloid-β.

    A team at The Rockefeller University used a new approach, known as iDISCO, that makes brain tissue transparent to permit the capture of detailed three-dimensional views of amyloid-β plaques within mouse and human brains. Their results are described July 14 in Cell Reports.

    Thomas Liebmann, the lead author, and his colleagues also used iDISCO to examine small blocks of frozen tissue from deceased Alzheimer’s patients, and found that the human plaques were larger and more complex than those from the mice. This discovery could aid researchers in establishing different categories for the disease based on a patient’s symptoms and the plaques within his or her brain. The relationship between plaques and dementia is poorly understood currently; the two do not always occur together.

    “A better understanding of these plaques, as well as other key features of Alzheimer’s in the brain, might contribute to efforts to develop better targeted drugs, or allow us to rethink the drugs we have now—that’s what we hope for,” says corresponding author Marc Flajolet, a research assistant professor in Paul Greengard’s Laboratory of Molecular and Cellular Neuroscience.

    This work was done in collaboration with Marc Tessier-Lavigne’s Laboratory of Brain Development and Repair and with assistance from the university’s Bio-Imaging Resource Center.

    Funding statement: This work was supported by the Fisher Center for Alzheimer’s Research Foundation, the Cure Alzheimer’s Fund, the NIH (NIA grant AG09464), and the Empire State Stem Cell Fund (NYSDOH contract #C023046).

    See the full article here .

    Please help promote STEM in your local schools.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 10:54 am on July 8, 2016 Permalink | Reply
    Tags: , Lillian Cohn, Rockefeller University,   

    From Rockefeller: Women of Science – “2016 David Rockefeller Fellowship awarded to graduate student Lillian Cohn” 

    Rockefeller U bloc

    Rockefeller University

    July 8, 2016
    Alexandra MacWade

    1
    Agata Smogorzewska, associate professor and head of the Laboratory of Genome Maintenance, presents Lillian Cohn with the fellowship citation.

    Lillian Cohn, a graduate fellow in Michel Nussenzweig’s Laboratory of Molecular Immunology, has been awarded the 2016 David Rockefeller Fellowship, given annually to an outstanding third-year student for demonstrating exceptional promise as a scientist and a leader.

    The fellowship was established by alumni in 1995 as an expression of gratitude for Mr. Rockefeller’s role in founding the university’s graduate program and for his commitment to its success. Mr. Rockefeller, who has served for more than 75 years on the university’s board of trustees, and celebrated his 100th birthday last summer, has said that few honors have meant so much to him as the creation of this award.

    Ms. Cohn, who grew up in Seattle, initially planned to go to medical school. She majored in biology and was a pre-med student at Brown University, but as time went on, she found herself drawn more to bench science. “Patient care was still a priority to me, but instead of approaching it as one doctor to one patient, I wanted to do science that could reach many people at once,” she says.

    After graduating from Brown, Ms. Cohn worked at the biotechnology firm Genentech for two years. She knew Rockefeller well—her grandfather Zanvil A. Cohn had a lab here until his death in 1993—and joined the graduate program in 2013.

    “Rockefeller is an incredible place,” she says. As an undergraduate, Ms. Cohn enjoyed the open curriculum at Brown, which allows students to create their own programs of study. That same kind of flexibility attracted her to Rockefeller. “There are no departments or bureaucracy here. You find your own way, and the student is driving the program,” she says.

    Much of the research in the Nussenzweig lab focuses on the biology of HIV or the development of new therapies against the virus, including broadly neutralizing antibodies and vaccines. Ms. Cohn’s work is focused on figuring out why there isn’t yet an effective cure for the disease.

    Although HIV can be controlled with drugs, HIV-positive individuals will develop AIDS if therapy is discontinued. That’s because there’s a number of cells in their bodies that harbor HIV and remain undetected by the immune system. “These cells don’t get killed; they just hang out,” Ms. Cohn says. “If the therapy is stopped, they’re lying in wait, like sleeper cells.” Ms. Cohn is studying and characterizing these cells as a way to understand how to cure HIV.

    Outside the lab, she is an enthusiastic volleyball player—she’s captain of a team that plays through a league in Manhattan—and an active volunteer. In addition to her work through New York Cares, she has spent time volunteering in prisons. While in California, she was involved with the Prison University Project at San Quentin State Prison, teaching English literature and biology to inmates. “It was a transformative experience, and it helped me understand the power of education in the lives of people who had limited access before,” she says. Here in New York, she has taught incarcerated high school students.

    Looking ahead, Ms. Cohn hopes to have her own lab. It’s a goal that not only reflects her love of science but also the obligation she feels to help other aspiring scientists, especially women. “It’s hard to be a woman in science,” she says. “I’ve had amazing women mentors who have inspired me every step of the way, and I want to pay it forward.”

    See the full article here .

    Please help promote STEM in your local schools.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 4:39 pm on May 23, 2016 Permalink | Reply
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    From Rockefeller: “New method gives scientists a better look at how HIV infects and takes over its host cells” 

    Rockefeller U bloc

    Rockefeller University

    May 23, 2016
    No writer credit found

    1
    Cell to cell: When HIV infects a cell, it programs the cell to express the viral protein Env, which the virus uses to spread to neighboring cells. Above, Env (red) produced by one infected cell has recruited other, uninfected cells, causing them to fuse, and their nuclei (blue) to cluster.

    Viruses attack cells and commandeer their machinery in a complex and carefully orchestrated invasion. Scientists have longed probed this process for insights into biology and disease, but essential details still remain out of reach.

    A new approach, developed by a team of researchers led by the Rockefeller University and the Aaron Diamond AIDS Research Center (ADARC), offers an unprecedented view of how a virus infects and appropriates a host cell, step by step. In research published* May 23 in Nature Microbiology, they applied their method to HIV, a virus whose genome is less than 100,000 the size of ours.

    “HIV is truly an expert at living large on a small budget,” says first author Yang Luo, a postdoc at ADARC and a former graduate student at Rockefeller University. “We asked the question, how does such a compact virus manipulate the host cell to gain entry and replicate itself, all while escaping the immune system?”

    Mapping HIV’s ‘interactome’

    The study focused on two viral proteins known to bring about HIV’s infection of human white blood cells. The first one, called envelope or Env, sits on the surface of the virus and, by binding to receptors on the host cell, helps the membrane that encapsulates the virus fuse with the cell’s outer membrane. A second protein, Vif, destroys an enzyme that host cells produce to defend themselves against the virus.

    In an effort to better understand how these two proteins function, the team wanted to map their interactome—meaning all the proteins with which they associate within a host cell. To accomplish this, the researchers needed to devise a way to isolate clusters of interacting proteins from cells during different stages of infection. Such experiments can be done by introducing a genetic sequence into the viral genome—a “tag” that acts like a piece of molecular Velcro, allowing one viral protein to be yanked out along with all the other proteins associated with it.

    2

    It sounds simple, but making it work took a decade.

    “Inserting a tag sequence into small viruses is a challenge to begin with,” says corresponding author Mark Muesing, a principal investigator at ADARC. “If you disrupt their nucleic acid and protein sequences, you can easily compromise the virus’s ability to replicate. And HIV represents a particular challenge because it can quickly revert back to its original sequence.”

    “We developed a technique to find places in the HIV genome where we can insert stable tags without affecting the virus’s capacity to proliferate. In effect, this allowed us to expand cultures of the infected cells along with the tagged viral protein,” he added.

    The host’s contribution

    Next, the researchers infected human cells with viruses carrying the tagged protein sequences, and were able to pull out and identify a large number of host proteins directly during the infectious process. This provided the first evidence that many previously underappreciated host proteins interact with the viral machinery during replication.

    “Imagine you have a factory assembly line where only one component of, say, the stamping machine, actually touches the product,” says co-author Michael Rout, professor and head of Rockefeller’s Laboratory of Cellular and Structural Biology. “Other parts support and power the stamp. Likewise, within an infected cell, we can identify the components of a particular cellular machine, not just the piece that comes in contact with the viral protein.”

    “Every host protein we pull out generates new questions,” adds co-first author Erica Jacobs, a research associate in Brian Chait’s lab. “Does it help the virus invade and coopt the host to replicate itself? Or does it harm it? The answers will not only help us understand the virus, but also shed light on our cells’ ability to defend themselves.”

    One important discovery has already emerged from the lists of proteins. Viruses, including HIV, often attack as so-called virions, which are individual packets of protein and genetic code. But they can also pass directly from an infected to an uninfected cell, a more effective mode of transmission. To do so, the virus appears to use host proteins to construct a platform, a close junctional surface, between cells.

    From the list of proteins that interact with Env, the researchers have identified cellular proteins predicted to contribute to this platform between cells. Because this route of transmission protects the virus in a sequestered environment, away from host defenses, the new findings may aid in the development of future anti-HIV therapies.

    A live infection, step by step

    According to co-author Brian Chait, Camille and Henry Dreyfus Professor and head of the Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, the new approach offers a rare glimpse into the process by which HIV invades and resurrects itself within a cell.

    “Often, studies of this sort are done with viral proteins in the absence of a true viral infection “However, because viral infections are exquisitely orchestrated events, you are likely to miss all kinds of important details if you study the action of these proteins out of their proper context.”

    “Deciphering the intricacies of virus-host protein interactions in space and time during the progression of an infection is remarkably powerful” says co-author Ileana Cristea, an associate professor of molecular biology at Princeton University. “The challenge is to discover which precise interactions are the critical ones.”

    Todd Greco, a co-first author, and an associate research scholar and lecturer in molecular biology in Cristea’s lab, says that “even for host proteins within the same family, their relative stability within HIV-1 protein complexes can be very different. More broadly, by understanding these mechanisms we will better understand the coordinated responses of cells.”

    *Science paper:
    HIV–host interactome revealed directly from infected cells

    See the full article here .

    Please help promote STEM in your local schools.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
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    From Rockefeller U: “Scientists find evidence that cancer can arise from changes in the proteins that package DNA” 

    Rockefeller U bloc

    Rockefeller University

    May 12, 2016
    No writer credit found

    newswire@rockefeller.edu
    Contact: Eva Kiesler |
    212-327-7963

    1
    Stuck dividing: In some cancers, including chondroblastoma and a rare form of childhood sarcoma, a mutation in histone H3 reduces global levels of methylation (dark areas) in tumor cells but not in normal cells (arrowhead). Rockefeller scientists found that the mutation arrests the cells in a proliferative state to promote tumor development.

    A mutation that affects the proteins that package DNA—without changing the DNA itself—can cause a rare form of cancer, according to new findings* in this week’s Science from researchers at Rockefeller University.

    The mutation is present in histones, the protein scaffolding around which DNA wraps. Researchers have known for some time that histones play a role in switching genes on or off in cells by exposing or covering up various parts of the genome, for instance. But they are just beginning to learn about how changes to these non-DNA structures can affect development and health—a field known as epigenetics—and how they are regulated. Now, for the first time, they’ve shown that a change to the structure of a histone can trigger a tumor on its own.

    “This is the first study to show that a genetic change to non-DNA structures in the cell—histones—is enough to cause cancer, with no other cooperating DNA mutations,” says co-author Chao Lu, a postdoctoral fellow in the lab of C. David Allis, Tri-Institutional Professor and Joy and Jack Fishman Professor in the Laboratory of Chromatin Biology and Epigenetics at Rockefeller University.

    A surprising source

    In earlier work, other researchers had found that in approximately 95 percent of samples of chondroblastoma, a benign tumor that arises in cartilage typically during adolescence, carry a mutation in a histone protein called H3.

    To explore whether and how the mutation causes the tumor, the researchers inserted the H3 histone mutation into mouse mesenchymal progenitor cells (MPCs), which generate cartilage, bone and fat. They then watched these mutant cells lose the ability to differentiate in the lab. Next, they injected the mutant cells into living mice, and the animals developed the tumors rich in MPCs, known as an undifferentiated sarcoma.

    “Although researchers knew that a certain type of tumor—chondroblastoma—carried a mutation in the H3 histone and no other mutation, this is the first study to show that the mutation indeed causes tumors, even without any other DNA mutation present,” says Lu.

    Next, the researchers tried to understand how the mutation causes the tumors to develop. They found that, when the mutation occurs, the cell becomes locked in a proliferative state—meaning it divides constantly, leading to tumors. Specifically, the mutation inhibits enzymes that normally tag the histone with chemical groups known as methyls, allowing genes to be expressed normally.

    In response to this lack of modification, another part of the histone becomes over-modified, or tagged with too many methyl groups. “This leads to an overall resetting of the landscape of chromatin, the complex of DNA and its associated factors, including histones,” says co-author Peter Lewis, a former postdoctoral fellow in the Allis lab and currently an assistant professor at the University of Wisconsin-Madison. This “resetting” is what locks the cell into its proliferative state.

    A new target

    The findings suggest that researchers should be on the hunt for more mutations in histones that might be driving tumors, says Lu. Meanwhile, he and his colleagues are trying to learn more about how this specific mutation in histone H3 causes tumors to develop. “For instance, we want to know which pathways cause the mesenchymal progenitor cells that carry the mutation to continue to divide, and not differentiate into the bone, fat, and cartilage cells they are destined to become,” he says.

    Once researchers understand more about these pathways, says Lewis, they can consider ways of blocking them with drugs, particularly in tumors such as MPC-rich sarcomas—which, unlike chondroblastoma, can be deadly. In fact, drugs that block the pathways may already exist and may even be in use for other types of cancers.

    “One long-term goal of our collaborative team is to better understand fundamental mechanisms that drive these processes, with the hope of providing new therapeutic approaches,” says Allis.

    This research was supported by The Rockefeller University, a startup provided by the Wisconsin Institute for Discovery, The Greater Milwaukee Foundation, the Starr Cancer Consortium, the Sidney Kimmel Foundation, and the National Institutes of Health (grants P01CA196539, DP2OD007447, R01GM110174, DP2CA174499, K08CA151660, K08CA181475, and P30CA008748).

    *Science paper:
    Histone H3K36 mutations promote sarcomagenesis through altered histone methylation landscape

    See the full article here .

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    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 6:35 am on February 6, 2016 Permalink | Reply
    Tags: , CRISPR-Cas, Rockefeller University   

    From Rockefeller: “A newly discovered form of immunity helps explain how bacteria fight off viruses” 

    Rockefeller U bloc

    Rockefeller University

    A newly discovered form of immunity helps explain how bacteria fight off viruses

    February 4, 2016
    Eva Kiesler | 212-327-7963

    When seeking to protect themselves from viruses, some bacteria use a seemingly risky strategy: They wait until the invading virus has already begun to replicate. Research at The Rockefeller University shows how the microbes use two newly identified enzymes to fight off an infection even after delaying action.

    “A viral infection can kill a bacterial cell—or in some cases, the viral genetic material can provide benefits, such as protection against other viruses. Harmful viruses immediately begin replicating, but beneficial ones implant themselves into the bacterial genome,” says Luciano Marraffini, assistant professor and head of the Laboratory of Bacteriology. “By using a wait-and-see approach, and tolerating the initial phase of the infection, the bacteria are able to make an intelligent choice.”

    The research, published this week in Cell, helps explain how bacteria manage to clear a harmful infection in spite of their slow response. In the future, it might inform the development of new ways to combat infectious disease, among other potential applications.

    A last-minute defense

    The study zeroes-in on two enzymes, Csm3 and Csm6, which are part of a bacterial immune system known as CRISPR-Cas. When these enzymes swing into action during the late phase of infection, they cut up viral RNA.

    The CRISPR (clustered regularly interspersed short palindromic repeats) system is a type of adaptive bacterial immune response that relies on sections of DNA containing sequences matching those in viral genetic code. CRISPR-associated genes use these sequences as guides to target invaders for destruction.

    Typically, CRISPR defense systems attack and destroy the viral DNA within minutes after it has been injected into the bacterial cell, so the invading virus doesn’t get a chance to replicate. However, the specific type of CRISPR investigated in the study—called type III CRISPR-Cas system—waits for the virus to replicate and mounts its attack during a later phase of the infection, after the viral DNA has been copied and is being transcribed into RNA.

    “It appears that type III CRISPR-Cas actually needs the virus to produce RNA before it can target and destroy the viral DNA,” says Wenyan Jiang, a graduate student who is the paper’s first author. “As a result, the system has to deal with hundreds of viral DNA strands instead of one, and can take up to nine hours instead of minutes to clear the infection.”

    An extra safeguard

    There is an inherent peril in waiting until this point, and because of the large number of viral genomes present, the typical DNA-cutting enzymes employed by CRISPR-Cas systems can’t stop the infection alone. So, type III CRISPR-Cas also uses the enzymes Csm3 and Csm6 to target the viral RNA, the researchers found.

    To observe this RNA-focused defense in action, Marraffini, Jiang, and Poulami Samai, a research associate in the lab, generated a mutated form of Staphylococcus epidermidis bacteria that lacked the Csm3 and Csm6 enzymes. When they infected both the mutant and the normal bacteria with a virus, the mutant population succumbed to it.

    The research clarifies how this CRISPR-Cas strategy functions, and also has potential implications for biotechnology and medicine. Because it can make precisely targeted cuts on genomes, CRISPR’s DNA-cleaving abilities have proved useful in developing genetic engineering techniques. Understanding how CRISPR RNA-cutting enzymes work may be useful to manipulate the RNA content of human cells, Marraffini says.

    “The study also advances our knowledge about how bacteria interact with their viruses, which is essential for understanding bacterial pathogenesis,” says Marraffini. “The viral genetic material can increase the virulence of pathogens, and at the same time viruses can be used to kill pathogenic bacteria in the clinic. Understanding the molecular mechanisms at play in the bacteria–virus interactions can help us combat infectious disease.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

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    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 1:25 pm on December 17, 2015 Permalink | Reply
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    From Rockefeller: “Experiments explain the events behind molecular ‘bomb’ seen in cancer cells” 

    Rockefeller U bloc

    Rockefeller University

    December 17, 2015
    Katherine Fenz | 212-327-7913

    1
    Tug of war: A chromatin bridge is formed as cells whose chromosomes are fused attempt to divide. The resulting daughter cells contain damaged DNA, which may serve as a precursor to cancer.

    Since scientists have begun sequencing the genome of cancer cells, they have noticed a curious pattern. In many different types of cancers, there are cells in which a part of a chromosome looks like it has been pulverized, then put back together incorrectly, leading to multiple mutations. For years, this phenomenon puzzled scientists. But new research from The Rockefeller University suggests an explanation for this strange molecular explosion that serves as a precursor to cancer.

    “The ‘old’ idea in cancer is that it arose from a first bad mutation, and then a second mutation, and a third, and so on, until the cells divide uncontrollably, leading to cancer,” says Titia de Lange, Leon Hess Professor and head of the Laboratory of Cell Biology and Genetics, who led the study. “This is a whole new view of how cancer can arise—a bomb goes off in part of a chromosome, and you get multiple mutations at the same time. These latest findings reveal the molecular details behind that bomb.”

    The study, published December 17 in Cell, describes the cellular events leading up to the phenomenon dubbed chromothripsis. However, these insights into the origins of chromothripsis came from an investigation into another molecular event that can lead to cancer, known as telomere crisis.

    Telomere crisis results when the protective caps at the end of chromosomes, known as telomeres, become shortened as a result of cell divisions. With less DNA present in telomeres, it becomes harder to prevent separate chromosomes from attaching to each other. If those abnormal cells survive and continue to divide, they can give rise to cancer.

    The researchers recreated telomere crisis in human cells by blocking the protein complex that prevents telomeres from fusing and disabling some of the molecular pathways that protect cells from turning cancerous. First author John Maciejowski, a postdoc in de Lange’s lab, filmed the events that followed.

    For a long time, researchers believed that once two chromosomes fused together at their telomeres, they would eventually break apart during cell division. But the researchers found that’s not what happened at all. Instead, cells with fused chromosomes continue to divide with their chromosomes attached. Once division is complete and the new daughter cells try to move away from each other, the piece of chromosome they share becomes stretched, forming what’s known as a chromatin bridge. “I think of it as a balloon that’s been pinched in the middle, and the two outer circles are pulling away from each other,” says de Lange. “Or like a tug of war, and each cell represents the opposing team, and the rope gets stretched and stretched and stretched.” The chromatin bridge can reach 0.2 millimeters—an unheard of size at the cellular level.

    Eventually, that bridge is broken down by one of the enzymes designed to target unfriendly DNA, such as that from viruses. And here, the researchers got a surprise—they discovered the enzyme that degrades the bridge DNA, TREX1, is normally present outside the nucleus that contains chromosomes. But as the two attached cells march away from each other, stretching the bridge DNA, that tension creates tiny tears in the membrane surrounding the nucleus, through which TREX1 enters and breaks down the chromatin bridge.

    Once TREX1 causes the chromatin bridge to disintegrate, the two daughter cells spring away from each other. Each carries some of the bridge’s DNA fragments, which the cells then try to put back together. Some cells die from the trauma of this event, but others survive and divide, spreading the damaged DNA, which may contain shuffled portions, or have lost some of the genes that suppress cancer. In other words, this chain of events creates chromothripsis.

    “The findings will hopefully help inform scientists’ understanding of the early molecular events that can lead to cancer, which may one day inform new methods to diagnose early stages of the disease,” says de Lange.

    De Lange and Maciejowski collaborated on this project with Peter Campbell and Yilong Li from the Wellcome Trust Sanger Institute in Cambridge, UK, as well as Nazario Bosco at Rockefeller.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
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