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  • Rockefeller Scientists Discover a Surprising New Cancer Gene | Newswire
    are used to turn normal cells into cancer cells These observations suggested at least a supplementary role for persistently activated Stat3 in tumor development The new research showing that activated Stat3 could by itself act as the transforming agent was performed in Darnell s laboratory which discovered the Stats and pioneered studies of the activation of these proteins The paper s first author Jacqueline F Bromberg M D Ph D is a postdoctoral fellow in Darnell s lab and an assistant professor at Memorial Sloan Kettering Cancer Center where she conducts studies of and treats breast cancer patients with Larry Norton M D Normally Stat proteins are inactive until cells receive an outside stimulus by such proteins as interferon erythropoietin Epo growth hormone or many other proteins that circulate in the body The active Stat then moves to the nucleus to turn quiescent genes on After a short period of activity the Stats become inactive again Therefore to study persistently active Stat3 the lab had to find a way to make a Stat3 molecule that would be constantly active Melissa Wrzeszczynska Ph D a co author and postdoctoral fellow in the Darnell lab suggested that a particular genetic change be made in the Stat3 gene that might cause cells with this altered gene to make Stat3 protein that would be active without any outside stimulus The suggestion worked and the researchers called this new persistently active molecule Stat3 C C because the new Stat3 proteins had two extra residues of the amino acid cysteine Cells with Stat3 C grew in a cancerous way in soft agar a jellylike substance in which cancer cells but not normal cells can grow and these cells also caused tumor development in nude mice animals that accept foreign cells and can therefore be used to

    Original URL path: http://newswire.rockefeller.edu/1999/08/06/rockefeller-scientists-discover-a-surprising-new-cancer-gene/ (2016-02-13)
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  • Discovery helps explain how B cells adapt to their targets | Newswire
    nodes and spleen Within germinal centers the B cells evolve The gene responsible for producing their antibodies mutates rapidly one million fold faster than the normal rate of mutation in the human body and the cells proliferate Then the B cells capable of producing antibodies with the highest affinity to the antigen are selected These cycles of mutation proliferation and selection happen over and over again Over time a few lines of high affinity B cells come to dominate the germinal centers Gitlin says Their current findings shed light on how the higher affinity B cells out compete lower affinity cells Ultimately the high affinity B cells survive and can protect the body should the same microbe be re encountered later on Vaccines take advantage of this process using weakened versions of pathogens to imitate an infection As a result a better understanding of how the immune system adapts its defenses will help with vaccine development including one against HIV In research described this week in Nature Gitlin and colleagues at Rockefeller looked at what happens to B cells during their time in the two zones of the germinal center In the dark zone B cells mutate and proliferate before traveling to the light zone where those with antibodies that bind best to the microbial antigens are selected The B cells then continue to divide returning to the dark zone While in the light zone the B cells pick up bits of antigen from the invader and display them on their surface The key finding is that specialized T cells in the light zone recognize higher affinity B cells based on the amount of antigen those B cells display In response the T cells provide a stronger signal to those higher affinity B cells instructing them to stay longer in

    Original URL path: http://newswire.rockefeller.edu/2014/05/06/discovery-helps-dxplain-how-b-cells-adapt-to-their-targets/ (2016-02-13)
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  • Potent antibodies neutralize HIV and could offer new therapy, study finds | Newswire
    antiretroviral drugs require daily intake These especially potent antibodies were only recently discovered some of them by several of Klein s colleagues in the Nussenzweig laboratory Called broadly neutralizing antibodies they were identified and cloned from HIV infected patients whose immune systems showed an unusually high ability to neutralize HIV In recent years the potent antibodies were found to prevent HIV from infecting non human primates demonstrating the possibility for a vaccine in humans But they were thought to have little or no effect on established infections Antibodies had been written off as a treatment for HIV AIDS because previous studies showed only a limited effect on controlling the virus says Klein But that was before these more potent antibodies were discovered We wanted to readdress this question using these new tools HIV 1 is notorious for evading the immune system s attacks by constantly mutating but the new antibodies are able to throw a wrench in that strategy The key is in the combination The antibodies target HIV 1 s surface protein gp160 a large molecule that forms a spike that seeks out host cells and attaches to them One antibody alone wasn t enough to quell the virus neither was a mix of three But five of them in unison proved too complicated for gp160 to mutate its way out of The researchers used humanized mice for the study provided by Alexander Ploss in the Laboratory of Virology and Infectious Disease because normal mice don t have the right receptors to be infected with HIV 1 Although HIV 1 infection in humanized mice differs in many important aspects from infection in humans the results are encouraging to investigate these antibodies in clinical trials says Klein It also may be that a combination of antibodies and the already established

    Original URL path: http://newswire.rockefeller.edu/2012/11/06/potent-antibodies-neutralize-hiv-and-could-offer-new-therapy-study-finds/ (2016-02-13)
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  • Florian Klein | Newswire
    class of especially potent antibodies is effective at neutralizing HIV infection in mice for a 60 day period longer than current antiretroviral drugs which require daily application The antibodies which suppressed the virus when used in combination could one day be given to humans to treat the disease More Tags antibodies Florian Klein HIV Michel C Nussenzweig Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics

    Original URL path: http://newswire.rockefeller.edu/tag/florian-klein/ (2016-02-13)
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  • Many Immune Cells Are Fine-tuned to Prevent “Friendly Fire” | Newswire
    by which they understand the system It is quite striking that what is being targeted so often is not the B cell per se but a specific part of the antibody the receptor that the cell produces Casellas says It is a much finer distinction one that the body makes more than most of us suspected B cells in humans and other vertebrates create antibodies with surface receptors that fit specific antigens When a foreign substance invades the body it is the antigen that selects the B cell with the proper antibody which causes the cell to multiply to launch an immune response Although there are many B cells each one produces only one specific antibody The body manages to create a huge number of unique antibody molecules with a relatively small number of genes by recombining several gene segments into a patchwork gene that encodes a Y shaped antibody with a highly specific receptor on its arms The antibodies are randomly made to fit any conceivable antigen they might encounter This random production inevitably creates antibodies that will attack the body s own proteins meaning that a significant number of immune cells are potentially harmful To address this threat the body employs various mechanisms to prevent this from happening of which four have been discovered so far Three of the four involve targeting the B cell before it develops enough to produce the harmful antibody In some cases the body simply destroys the B cell a process called central deletion This method was first proposed by Rockefeller University Nobel Prize winner Joshua Lederberg in 1959 but not proven until about 10 years ago More recent research has uncovered three other strategies Some cells undergo a process called anergy in which the cells are disabled and die a slow death In rare cases called ignorance the cells simply fail to respond to the antigen for which they were designed The fourth mechanism receptor editing is the only one that alters the antibody and allows the cell to move on The modification to the cell in receptor editing is not extensive But since antibodies are so highly specialized a minor change can still have a big impact much the way a slight imperfection on a key can render it useless Although changing the cells in such a manner benefits the body the editing itself is haphazard in that the alteration is not guided so that a specific sequence is inserted when the new gene is patched together Rather the body splices in a random sequence and sees if it works If the cell is still self reactive with its new receptor it once again is subject to one of the body s four protective mechanisms Casellas and his colleagues conducted their experiment with genetically modified mice that allowed them to determine whether a specific DNA stretch had been changed during immune system development They inserted a human DNA sequence into a precise spot in the mouse genome and waited to see

    Original URL path: http://newswire.rockefeller.edu/2001/02/22/many-immune-cells-are-fine-tuned-to-prevent-friendly-fire/ (2016-02-13)
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  • receptor editing | Newswire
    genetic code revised during a halt in their development scientists at Rockefeller University and three other institutions have found The study is the first to show that this phenomenon called receptor editing plays a major role in the creation of the body s huge antibody array More Tags antibodies B cells Michel C Nussenzweig receptor editing Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video

    Original URL path: http://newswire.rockefeller.edu/tag/receptor-editing/ (2016-02-13)
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  • 400 High School Students Attack Foreign Invaders!: RU Mirsky Lecture on the Body’s Immune Response | Newswire
    which allows lab members to analyze the function of specific genes in the context of the living organism Nussenzweig earned his Ph D at The Rockefeller University in 1981 A year later he received his M D from New York University School of Medicine Antibodies and Genes at 10 30 a m is the first of two lectures that will explore the immune system s ability to recognize almost any type of invading foreign material and the molecular mechanisms that generate antibody diversity B lymphocytes are designed to recognize this threatening world of potential invaders and are capable of producing antibody molecules with an almost limitless variety of specificities Once generated these antibodies may either seek out and directly destroy an antigen the molecular signature of microbial or viral invaders or label it so that a white blood cell or macrophage can engulf and remove the intruder from the body By the late 1960s it had become clear through scientific investigation that stem cells primitive cells that develop into specialized cells give rise to all blood cells including two broad groups of lymphocytes B cells and T cells The day s second lecture B Cell Development and the Antibody Response at 1 30 p m will focus on B lymphocyte development B cells which are derived from maturing bone marrow stem cells and produce antibodies that bind to extracellular pathogens such as bacteria and mark them for attack by other cells are distributed by the blood and make up 20 to 30 percent of the circulating lymphocytes Lymphocytes continuously circulate through the body s vascular and lymphatic systems stopping periodically in the lymphoid organs lymph nodes and spleen as they patrol for foreign invaders In contrast to B lymphocytes T cells which arise in the thymus and comprise 70 to 80 percent of the circulating lymphocytes can handle such intracellular pathogens as viruses in addition to such intracellular parasites as tuberculosis T cells also secrete molecules known as lymphokines which direct the activity of B cells other T cells and other parts of the immune system All lymphocytes are studded with sensitive cell surface receptors organs of touch so subtle and precise that they can detect changes at the level of a single atom The receptors on the surface of B lymphocytes are much like those on T cells each set of receptors is genetically programmed to recognize a different bit of bacteria or pathogens But B cells can also produce quantities of antibodies receptor like molecules that are free to move out of the cell since they lack an anchor in the cell membrane When a B cell grabs hold of an antigen and gets turned on it divides and differentiates into a plasma cell which churns out millions of these identical foe specific molecules and releases them into the bloodstream where they can latch onto viruses bacterial proteins and toxins The Mirsky Christmas Lectures were established in 1959 by the biochemist and RU librarian who modeled the series

    Original URL path: http://newswire.rockefeller.edu/1998/12/24/400-high-school-students-attack-foreign-invaders-ru-mirsky-lecture-on-the-bodys-immune-response/ (2016-02-13)
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  • Alfred E. Mirsky Christmas Lecture Series | Newswire
    of the leaders in the field of immunology will share his latest research with 400 area high school science students at the 39th Annual Alfred E Mirsky Christmas Lecture Series on Science The Rockefeller University Caspary Hall 1230 York Avenue at 66th Street Student attendance is by ticket only Press coverage is invited More Tags Alfred E Mirsky Christmas Lecture Series antibodies Michel C Nussenzweig Search for Categories Science News

    Original URL path: http://newswire.rockefeller.edu/tag/alfred-e-mirsky-christmas-lecture-series/ (2016-02-13)
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