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  • Nora Pencheva wins 2014 Weintraub Graduate Student Award | Newswire
    metastatic melanoma the most deadly type of skin cancer Looking for novel regulatory pathways involved in the cancer Pencheva has identified three microRNAs that promote metastasis in several types of melanoma by enhancing the invasive capacity of melanoma cells and the cells ability to recruit neighboring endothelial cells into the metastatic process Pencheva has found that the expression levels of these microRNAs could act as prognostic biomarkers in melanoma by determining if patients were at high risk for relapse Pencheva has also found that one of the microRNA targets apolipoprotein E ApoE is a potent suppressor of melanoma metastasis and that LXRβ a transcriptional activator of ApoE could be a viable target for treatment Pencheva earned her bachelor s degree in neuroscience from Kenyon College in Ohio and will graduate from Rockefeller with her Ph D in molecular biology in June She is also the recipient of an Anderson Center for Cancer Research Fellowship The Weintraub Award was established in 2000 and honors the late Harold M Weintraub a founding member of the Fred Hutchinson Cancer Research Center s basic sciences division who died from brain cancer in 1995 at the age of 49 Weintraub was an international leader in the field of molecular biology who among other contributions identified genes responsible for cell differentiation The award symposium will take place in May at the Hutchinson Center in Seattle where the recipients will participate in a scientific symposium and receive an honorarium from the Weintraub and Groudine Fund established to foster intellectual exchange through the promotion of programs for graduate students fellows and visiting scholars Pencheva is one of 13 recipients this year Pencheva is the ninth Rockefeller student to receive the Weintraub award Past recipients are Teresa Davoli Johannes Scheid Nadya Dimitrova Sung Hee Ahn Upton Vanessa Ruta Paul

    Original URL path: http://newswire.rockefeller.edu/2014/03/10/nora-pencheva-wins-2014-weintraub-graduate-student-award/ (2016-02-13)
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  • Nora Pencheva | Newswire
    Sohail Tavazoie s Laboratory of Systems Cancer Biology is one of 13 recipients of this prestigious award Her thesis project explores the molecular biology of metastatic melanoma the most deadly type of skin cancer More Tags Nora Pencheva Sohail Tavazoie Weintraub Graduate Student Award Search for Categories Science News Awards and Honors Campus News Grants Gifts Topics Video Archive 2015 2014 2013 2012 2011 more About Contact Follow rockefelleruniv Like

    Original URL path: http://newswire.rockefeller.edu/tag/nora-pencheva/ (2016-02-13)
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  • Weintraub Graduate Student Award | Newswire
    is one of 13 awardees all advanced graduate students at or near the completion of their studies in the biological sciences and chosen for the quality originality and significance of their thesis research More Tags HIV Weintraub Graduate Student Award March 2 2009 Awards and Honors Nadya Dimitrova wins 2009 Weintraub Graduate Student Award Nadya Dimitrova a graduate fellow in Titia de Lange s Laboratory of Cell Biology and Genetics

    Original URL path: http://newswire.rockefeller.edu/tag/weintraub-graduate-student-award/ (2016-02-13)
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  • New Rockefeller faculty member studies cancer metastasis | Newswire
    summer course on bacterial genetics at the University of Utah He considered a career in clinical medicine but found himself drawn to the lab even as he trained as a physician Following his internship and residency in internal medicine at Brigham and Women s Hospital he joined Memorial Sloan Kettering Cancer Center where he has been a postdoc since 2006 in the laboratory of Joan Massagué Tavazoie s research has led to the identification of three important microRNAs that regulate key genes that are active in cancer metastasis MicroRNAs are small molecules that regulate the expression of genes typically by interrupting the expression of proteins after the target gene s DNA has already been transcribed Tavazoie undertook a systematic analysis of more than 450 microRNAs in cells derived from human breast tumors and discovered two that suppress migration and invasion of metastatic cells and one that suppresses their proliferation and growth Further work led to the discovery of two target genes that one of these microRNAs acts on and that are required for metastasis in breast cancer the tumor type that Tavazoie has focused on thus far When you look at clinical tumors at time of initial diagnosis those patients whose tumors lose expression of these microRNAs are significantly more likely to develop future metastasis Tavazoie says They are prognostic At Rockefeller Tavazoie will pursue this line of inquiry using a systems biological approach that integrates molecular cellular animal and clinical observations with the goal of identifying and characterizing key molecular regulators as well as extending the work to other types of tumors particularly those of colon cancer Ultimately the research could lead to better tools for identifying patients at high risk for metastatic relapse as well better therapies for the prevention and treatment of metastasis Rockefeller is unique as

    Original URL path: http://newswire.rockefeller.edu/2008/09/16/new-rockefeller-faculty-member-studies-cancer-metastasis/ (2016-02-13)
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  • Rendering of ion channel suggests how neurons fire | Newswire
    the channels to open and close Changed channel Lipid molecules yellow and red are an integral part of the voltage dependent ion channel and confer stability to it MacKinnon s structural renderings show that lipid molecules are most dense in the concave semicircles between the voltage sensors In a November issue of Nature he and lab members Steve Long Xiao Tao and Ernest Campbell released new renderings of these channels that describe a possible mechanism for how the paddle carries its charged cargo through the channel as well as how the charged paddles are stabilized within the cell s membrane Along with his colleagues MacKinnon a Nobel laureate and an investigator at the Howard Hughes Medical Institute as well as the university s John D Rockefeller Jr Professor took advantage of the paddle s unique transplantability to create a hybrid ion channel one of only a handful of eukaryotic membrane proteins whose structures have been determined through recombinant expression In the presence of lipid molecules the hybrid ion channel formed a crystalline lattice that enabled MacKinnon and his team to describe the structure with unprecedented atomic detail Within the crystals the lipid molecules organized themselves around the several ion channel proteins forming a lipid bilayer that mimicked the channel s natural environment Knowing how the lipids organized themselves around the ion channel the researchers were then able to demonstrate how positively charged amino acids within the voltage sensor s paddle remained stable despite the potentially destabilizing forces surrounding them The structure also shows how movement of the gating charge across the membrane directly influences the opening and closing of the pore s gate Voltage dependent ion channels are important therapeutic targets for future treatment of pathological conditions such as epilepsy and cardiac arrhythmia The new methods being developed for eukaryotic

    Original URL path: http://newswire.rockefeller.edu/2007/11/30/rendering-of-ion-channel-suggests-how-neurons-fire/ (2016-02-13)
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  • Ion channels are key to estrogen’s effect on neurons | Newswire
    neurotransmitters How each neuron responds to the signals depends on a variety of factors but experiments showed that when neurons in the hypothalamic ventromedial nucleus VMN of the brain involved in the female sex drive were exposed to estrogens they became more responsive to neurotransmitters Donald Pfaff head of Rockefeller s Laboratory of Neurobiology and Behavior was interested in why this occurred In research in mice reported this fall in Brain Research lead author and senior research associate Lee Ming Kow found that the key was the sodium and potassium ion channels They generate the electric currents that propagate the neurotransmitter signals along the cell s membrane By modulating the ion channels ability to let electrical signals in and out of the cell estrogen caused the neurons to become highly excitable and that translated into increased sexual behavior in the mice Kow found that within five minutes of applying estrogens to the VMN neurons that the inward currents were enhanced and the outward currents were attenuated says Pfaff This makes the neurons more excitable and more responsive to neurotransmitters Looking closely at the sodium channels which control the inward current and the potassium channels which control the outward current they found that estrogens modulate the kinetics of each channel affecting how easily they open and shut While estrogens have been shown in other cells to affect sodium channels this was the first study to show that they can affect them in neurons It has long been understood that the action of estrogens in the VMN facilitates sexually receptive lordosis behavior in female mice through its activation of specific genes involved in reproduction But the new results suggest thatï ½s just half the story By increasing the excitability of those neurons in addition to their actions on gene transcription estrogens could

    Original URL path: http://newswire.rockefeller.edu/2006/12/06/ion-channels-are-key-to-estrogens-effect-on-neurons/ (2016-02-13)
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  • MacKinnon lab’s newest picture tells action potential story | Newswire
    charged sodium to flow into the negatively charged interior of the cell Almost instantaneously neighboring voltage dependent sodium channels Nav open in response allowing more sodium to enter creating an upset in the normal negative inside positive outside voltage common to all living cells As soon as the explosive cascade of sodium channeling begins hyper sensitive voltage dependent potassium channels Kv along the same cell s surface sense the catastrophic switching of the charge value inside the cell and in their own domino effect open up to allow positively charged potassium ions to quickly flow out of the cell This movement restores a cell s normal negative inside positive outside charge value The cell returns to its former calm The entire sequence of events takes only a few milliseconds and occurs tens of thousands of times every day in human beings and organisms of all varieties Without this hair trigger electrical system life would be more than calm There would be scant possibility of thinking breathing or movement A picture is worth a thousand differential equations The MacKinnon lab group responsible for the the voltage dependent potassium channel discoveries includes back row from left Roderick MacKinnon Vanessa Ruta Youxing Jiang and front from left Alice Lee and Jiayun Chen The burst associated with the paired activities of sodium and potassium voltage dependent ion channels underlies the theory of the action potential In 1952 scientists Hodgkin Huxley and Bernard Katz using the visible nervous system of squid explained the action potential as the basis for the generation and propagation of the nerve impulse Their landmark series of papers described the action potential in terms of mathematical equations Hodgkin and Huxley won the Nobel prize in 1963 Their theory became a cornerstone of cellular biophysics and set an entire field of scientists to work studying excitable membranes or the outer coats of cells associated with all nerve and muscle activities including the brain and the heart The three prescient scientists originally identified a feedback loop relating cell membrane permeability ability of a cell s coat to open up via a tiny device called an ion channel and voltage positive or negative charges one condition determines the next which in turn creates the first condition all over again After decades of studying the action potential scientists have shown that the permeability sets the membrane voltage In other words ion channels opened or closed positions have an impact on the charge value of the cell membrane Scientists understand how membrane permeability to ions sets the voltage Until now however no group of researchers had ever solved the riddle of how the membrane voltage determines the permeability completing the feedback loop The combination of a picture of the voltage dependent potassium channel at an atomic level and the functional and biochemical analysis by MacKinnon and his colleagues answers this question We can now see how membrane voltage will change the shape of this kind of potassium channel says MacKinnon causing it to open and close

    Original URL path: http://newswire.rockefeller.edu/2003/04/30/mackinnon-labs-newest-picture-tells-action-potential-story/ (2016-02-13)
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  • Hardworking sodium/ potassium pump fundamentally similar to free-flowing ion channel | Newswire
    normal conformational changes the coral toxin essentially turns them into channels The researchers specifically studied the sodium potassium pump the most common and arguably most important of the human ion pumps Its impaired activity is believed to underlie high blood pressure and it is the target of digoxin one of the most widely prescribed drugs for heart disease A closely related ion pump the hydrogen potassium pump controls the production of stomach acid and is targeted by new antacid drugs such as Prilosec A better understanding of the molecular workings of ion pumps may ultimately pave the way for better treatments for hypertension and heart failure and possibly other disorders We hope that palytoxin will give us a more detailed picture of the molecular mechanisms underlying the function of one of our body s most essential and remarkable microscopic machines the sodium potassium pump says Gadsby Gated community of the cell Unlike ion channels which permit the flow of just one specific type of ion most ion pumps transport different kinds of ions in opposite directions across cell membranes The sodium potassium pump for example passes three sodium ions out of the cell for every two potassium ions pumped into the cell Just how this uphill ion exchange is accomplished without downhill leakage was first proposed in the late 1950s in the alternating access model which hypothesized that ion pumps might allow the entrance and exit of ions at only one side of the membrane at a time rather like a revolving door In this model a pump acts like an ion channel with two gates one at either end that are constrained to open alternately but never at the same time one gate must close before the other can open But no concrete evidence in favor of this four decade old model existed until now David Gadsby left and Pablo Artigas Presto you re an ion channel To trick the sodium potassium pump into revealing its true ion channel nature Artigas and Gadsby applied palytoxin to cells and used electrophysiology specifically the patch clamp technique to detect its effects The patch clamp technique has enabled scientists to detect electrical currents produced by the flow of ions through a single channel yet it hasn t been able to detect a single working pump molecule This is because while a channel easily passes ions across the cell membrane at a rate of up to hundreds of millions of ions per second making a current that is readily detectable a pump has to work hard to move only hundreds of ions per second too few to produce a measurable signal So when the researchers added palytoxin to a single pump and observed its electrical signal immediately go from zero to almost a trillionth of an ampere they knew that what had been a hardworking pump had indeed been transformed into a free flowing channel What the toxin does is to allow the pump s two gates to be open at the same

    Original URL path: http://newswire.rockefeller.edu/2003/01/21/hardworking-sodium-potassium-pump-fundamentally-similar-to-free-flowing-ion-channel/ (2016-02-13)
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