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LUDWIG LINK | MARCH 2014 People on the Move the on People © Nobel Media 2013. Photo: Helena Paulin Strömbe Paulin 2013. Helena Photo: Media © Nobel QueenUppsala Silvia escorts of Sweden. Nobel Foundation Chairman of the Board Calle Heldin of Ludwig Royal the and of London Royal Society to the elected been has She science. to clinical forservices Empire British of the commander 2010,appointed was Karen January In cells. the even kill or growing from cells tumor stop could This cells. cancer in on back switch to help fordrugs searching are They cells. cancer in undermined is control this how and controlled how showing as such key several discoveries, made They’ve . fuels functions many of its loss the cancer, prevents how and gene the how investigating is team Her scientist. independent an as career her studying been has Karen ALL THE QUEEN’S MEN ALL THE QUEEN’S p53 since the early stages of stages early the since

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LUDWIG LINK | MARCH 2014 Awards and Distictions There, each recipient also will deliver an honorary lecture lecture honorary an deliver will also recipient each There, University. Rockefeller at Prize luncheon 2014, Wiley the at 11, April on year’s presented award of be This $35,000will inadequate oxygen delivery. by caused diseases on light shed and prevention, and treatment of cancer development and research guide aresure to field to this Peter’s contributions growth. runaway to support circuitry oxygen-sensing the co-opt frequently cells Cancer systems. of oxygen-sensing field to the contributions forhis Sciences Prize Biomedical in Wiley 13th of Annual the of winners four one also Peter is his research.”from directly benefit time in may who hospital the in patients after to look continues he but treatments, of cancer new development forthe potential have research outstanding his does director. only “Not honor,” Oxford’s Ludwig Lu, Xin said extraordinary by this recognized been has Peter’s work that delighted are “We diseases. these to treat manipulated be might they how and pathways these understand to how better on working is He role. important an plays cell the in of oxygen a lack where disease, cardiovascular or pulmonary and cancer as such of diseases development of the understanding to abetter led has This of oxygen. to alack respond they how especially and to them, available is oxygen much how detect body the in cells how on research pioneering forhis known best biologist molecular and acell Peteris scientist. and clinician outstanding this to awarded of honors aseries in latest the just is This to medicine. services forhis knighted Peterwas Sir list. 2014 the Year’s in II New Elizabeth Honours by Queen recognized been has PeterRatcliffe Oxford’s Ludwig A KNIGHT TO KNIGHT A REMEMBER

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LUDWIG LINK | MARCH 2014 Awards and Distictions DNA, and its connection to human cancer. to human connection its and DNA, of integrity the disrupt can that errors genetic repair of to cells ability repair, the mismatch concerns which DNA of field the in discoveries forhis recognized was He field. of the tools standard have become pioneered has he techniques of many the and , cancer has contributed enormously to our understanding of The recognition is Richard’s well deserved. research health. public and care health sciences, medical of the advancement to the contributions major have made who individuals recognizes that aprocess through members by active elected are members New medicine. and health of fields the in honors year.last highest of the one is This honored so of 70 one people of Medicine, Institute to the elected been has Diego San of Ludwig Kolodner Richard a directed has He of disease. drivers genetic the elucidate to DNA human map to of forefront efforts the at been has work His of disease. course the to change information that to how use and genome, human of the Bing’s research focuses on the growing understanding organization of eukaryotic genomes. transcriptional regulatory and sequences the large-scale of genome-wide distributions of regulatory factors, his original outstanding contributions to the analysis for lauded was Bing peers. by their members AAAS upon bestowed honor an afellow is as Election society. scientific general world’s largest the (AAAS), Science of Advancement forthe Association American of the afellow named been has Ren Bing scientist Ludwig MAKING AN IMPACT AN MAKING FELLOWSTELLAR

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LUDWIG LINK | MARCH 2014 News Roundup common types of cancer. The results could change the the change of could cancer. results The types common system is critical for preventing the development of 5 issue trigger: cancer. The findings, published in the apossible found they’ve say Hopkins Johns at scientists Ludwig but unknown, is cause Its women. middle-aged to young afflicts commonly most and States, United the in people 300,000 estimated an affects It death. cases, some in and, damage organ internal to serious lead progressive thickening andtightening of It the skin. can Scleroderma is an autoimmune disease that causes radiotherapy. of of interferon- expression boosts that pathway downasignaling shuts to radiation, exposed cells tumor in accumulates gene, by interferon-stimulated an expressed is which protein, LGP2 that shows study The tumors. human some in killing of radiation-induced keyare components interferons, and the genes they activate. Interferons called proteins by anti-viral signaling by inducing part in cells tumor kills radiation that suggest data Recent therapy. radiation resist cells such by which mechanism another report Khodarev Nikolai and researchers led by Ludwig ’s Ralph Weichselbaum of Sciences Academy National of the Proceedings the In cells. by tumor repair DNA to stepped-up attributed been traditionally has that quickly develop resistance to the therapy–a phenomenon many because control fortumor inadequate often is it but cells, tumor kills therapy Radiation GUILTY PARTY POSSIBILITIES OF GLIMMER of of Science β and blocks the cytotoxic effects effects cytotoxic the blocks and , also suggest that a normal immune immune anormal that suggest , also January 13 online issue 13 online January December , a team of, ateam

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LUDWIG LINK | MARCH 2014 News Roundup a gene that can determine variations in the body such as as such body the in variations determine can that a gene of form alternative an is which allele, an as known is copies of those Each parents. of its each from gene copy of every one inherits mammal Every Rickard. said into adulthood,” described—one that throughout persists development and been before never has that expression oflevel gene the at randomness afundamental have captured “We cells. single in of genes expression global the foranalyzing by lab Rickard’s developed technique new by apowerful possible made was discovery The people. different in severity in vary can genes aberrant of set by ashared caused disorders inherited why some and appearance, and biology in different so sometimes Science why. reasons to the His added just has of Ludwig this? Why is Sandberg Rickard twins. alike, they’re even if identical exactly are people two No Hopkins. Johns of Ludwig Ken Kinzler, co-director naturally,” check in said cancers keeping be may system treat cancer, adding to support the notion that the immune the emerging picture of harnessing the to and system immune of power the to the speaks study “This response from the patient’s immune system. a triggering produced, was protein of form the a foreign encodes When RPC1. the was present, however, called agene in amutation had patients NO TWO ALIKENO TWO helps explain why genetically identical animals are are animals identical why genetically explain helps recent study recent POLR3A , which , which in in 8 tumors to form on nerve tissue. tissue. nerve on to form tumors causing system, nervous the in growth cell disturbs that disorder genetic a neurofibromatosis, as such diseases, genetic of some understanding forour implications has also finding The fordisease. propensity and appearance in differ can twins why identical measure some in explains hair expression color. of allelic randomness essential The Ken Kinzler, Nickolas Papadopoulos, Shibin Zhou Vogelstein, Bert Diaz, Luis right. to Left team. Hopkins Johns Ludwig Ludwig Stockholm Ludwig Ilgar Abdullayer and Rickard Sandberg

LUDWIG LINK | MARCH 2014 News Roundup expanded C9orf72 RNAs. Selective silencing of atoxic silencing Selective RNAs. C9orf72 expanded antisense oligonucleotides to appears reduce levels of “Treatment with globe. the across ofto 1of ALS 20 cases and ALS, familial with to 40% linked to of be people seem frontotemporal dementia. Repeat expansions in the gene and ALS both in implicated is C9orf72 encoding gene The C9orf72. called aprotein encoding RNA normal the affecting without toxicremove RNA the could they that demonstrated team The down. RNA the and frontotemporalALS and dementia, selectively break of form common most to the contributes that toxic RNA antisense oligonucleotides the couldbuildup of impede called material of genetic segments that determined of Sciences Academy National of the astudy In personality or language. patients primarily experience deterioration in behavior, frontotemporal dementia, a form of dementia in which and to paralysis leading degenerate, cord spinal and brain the in neurons motor which in disease a fatal is It disease. Gehrig’s Lou as known also (ALS), sclerosis of lateral amyotrophic cause genetic common most the treating for novelstrategy a identified has that Cleveland and Clotilde Lagier-Tourenne of are a part team diseases history. Ludwig researchers Diego San Don neurological lethal We’re two to making closer astep YOU’RE HISTORY published online on October 29 , the researchers researchers , the in in Proceedings Proceedings

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LUDWIG LINK | MARCH 2014 News Roundup , the most common type of brain tumors, tumors, of brain type common most the glioblastomas, by which anovel mechanism uncovered Furnari, Frank and Web Cavenee, Mischel, Paul including Diego, San Ludwig from of Ateam researchers re-emerge. can cells What’s more, once the therapy has stopped, the cancer body. the in they’re present while drugs cancer evade can cells cancer Brain seek. and of hide game adeadly It’s inherited together. to be tend that variations of aset DNA is A haplotype chromosome. same the on together, haplotype, asingle as totheir ability discern which are variants inherited in limited extremely are methods these variants, genetic catalog precisely can methods sequencing current Although material. of genetic copies two inherit Humans discovery,” and Siddarth. research said genetic on effects have profound also will and practice clinical in genomics of utility forthe implications direct has advance “This medicine. of personalized acornerstone fordisease, risk individual aperson’s assess to better clinicians father. or enable will mother This individual’s an from comes sequence genetic particular a whether determine can Dixon Jesse and Selvaraj Siddarth Ren, Bing researchers Diego San by Ludwig developed technique anew HaploSeq, of care. standard of the part become could $1,000, sequencing about and for sequenced be could agenome cheaper.and Soon, faster getting are technologies sequencing reality. DNA a to becoming closer step one is medicine Personalized PLAYING GAMES FAMILY TIES 10 human migration patterns. donors with organs and help scientists better understand of matching process improve the genomes, of fetal contribute to disease. It could enable prenatal sequencing genes how on handle abetter to get researchers allowing HaploSeq provides of haplotypes genetic content, and the tumor continues growth. its removed, is treatment the When it. targets specifically that EGFRvIII gene, growth-enhancing their discard cells cancer brain the in published study Anew therapies. targeted evade can December 5 online issue

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LUDWIG LINK | MARCH 2014 News Roundup cancer cell metabolism to destroy tumors. to destroy metabolism cell cancer disrupt might that drugs fornew targets possible several uncovered researchers The growth. runaway their sustain to required materials raw and energy the to generate glucose metabolize they how change cells cancer which by a mechanism key identified Matsui Kenta and Cavenee Web Mischel, Paul glucose. from forgrowth materials raw Cell Metabolism Another study, published in the forpatients. of treatment course abetter determine doctors help may It therapies. to targeted resistant becomes why explain better findings drug.” study’s by the The indirectly sent being are that signals the sensing is DNA the that is theory the “But said. Paul understood,” not really is drug the sensing is DNA the by which mechanism “The which more effectiveare therapies desperatelyneeded. for cancer of abrain treatment future forthe implications huge has study this researchers, to the According Ludwig San Diego Paul Mischel Ludwig San Diego Cavenee Web

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Ludwig San Diego Frank Furnari October 17 online issue 17 online October

of of 11 Company News Company approved for the treatment of . treatment forthe approved immunotherapy an to well ipilimumab, likely to respond weremore cells of these lowof levels with asubgroup cancer patients. The researchers discovered that patients in rates survival poor with associated are and immunity antitumor decrease which cells, suppressor derived test measures a patient’s level of circulating myeloid- The Lesokin. Alex and Wolchok by Jedd MSK Ludwig at developed patients, forcancer test blood new important Serametrix Corporation has announced the launch of an and Ludwig MSK. MSK. Ludwig and the highly productive interaction between the company characterizes It of assays. suite existing to this addition important an be will test new The owns Serametrix. partly which 2009 Ludwig, in from licensed and MSK Ludwig at established know-how and technology on based assays profiling immunological of variety a offers Serametrix Jedd. said patients,” cancer in therapy immune of development clinical the in tool avaluable become to potential the has novel assay “This patients. cancer in of recurrence likelihood the to monitor by clinicians used be also may test the future, the In immunotherapies. of experimental development clinical in engaged companies drug to offered be initially will test The EXPANDING TOOLBOX

LUDWIG LINK | MARCH 2014 Company News Company Our collaboration will enable us to combine this novel this to us combine enable will collaboration Our cancer. lung non-small-cell in trials clinical early-stage in results promising shown has antigens, Ludwig several “CureVac’s immunotherapy platform, which is built upon of cancer. approaches holds great potential for the treatment Combining immunotherapy vaccines. RNActive immunotherapy treatment options involving CureVac’s of novel cancer testing clinical to enable Institute Research Cancer the and Ludwig with collaborating of immunotherapies The company based on RNA. is of class anew CureVac development the in apioneer is is trial The Trials CVC the Network. within sites at initiated been has tumors solid advanced with subjects in anti-PD-L1 (MEDI4736) (tremelimumab), and anti-CTLA-4 modulators, of of these two of acombination tolerability and safety the to evaluate designed trial first The prevent it from escaping the immune response. and fronts multiple on cancer aparticular to attack combinations of immunotherapies could enable scientists Developing system. immune treatments that use distinct yet potentially on effects complementary the Differentcancer immunotherapies aredesigned to have trials of optimal combinations of checkpoint inhibitors. forconducting aprogram have created MedImmune and Institute Research Cancer the therapy. Ludwig, of cancer acornerstone to become expected are immunotherapies, of cancer development forthe targets potential are that proteins modulators, checkpoint Immune THE RNA PEOPLE RNA THE MULTIPRONGED ATTACK

12 head of technology development. clinical investigators,” Skipper, Jonathan said Ludwig’s our and Ludwig and MedImmune at teams management interactive engagement among the clinical trials of ahighly aresult is and program forour milestone asignificant is agents investigational of two study complex of this implementation and approval successful Cancer Research Institute “The and MedImmune. by the provided is funding and by Ludwig sponsored or additional collaborative partnerships. collaborativeor additional partnerships. portfolios internal their via have access Institute Research Cancer and Ludwig to which agents other with combined CureVac’s CV9202, using drug, Network investigational immunotherapy combinations through their CVC Trials of cancer studies clinical conduct may Institute Research Cancer the and Ludwig collaboration, the Under Skipper. Jonathan said patients,” of cancer number to alarger agents these of impact clinical the extend can this whether to test modulators, checkpoint immune as such approaches, withtechnology different immunotherapeutic Ludwig Jonathan Skipper

LUDWIG LINK | MARCH 2014 Ask aScientistAsk Why do we die from cancer? Ludwig MIT Ludwig improve survival. patient will aggressive becoming from ones benign preventing aggressive cells over time. Targeting aggressive cells and cells to regenerate benign remaining enabling ones, targeting aggressive cancer cells may not target benign Treatments states. aggressive and benign between switch can cells cancer because treat to is difficult Cancer Stockholm Ludwig deaths. cancer prevent us to help will differences genes causing Identifying survival. these prognostic high and tumors early-stage with children in those from with specific chromosomal abnormalities different is associated neuroblastoma in prognosis poor example, For genetics. tumor with correlates cancer in Survival Ludwig this dies. machinery wonderful prevents the from body producing or consuming energy, However, life expectancy. cancer their once prolong or cure people can treatments Medical fail. alterations genetic repairing systems the when occurs cancer and interfere, can malfunctions genetic Tiny second. every cells are renewed 4million energy: produces and consumes of cells, of trillions body, composed human The CHRISTINE CHAFFER CHRISTINE WALLIS KARIN NATHALIE DEMOTTE 13

LUDWIG LINK | MARCH 2014 Q&A withQ&A Xing Chen, vice president and chief investment officer of the LICR Fund also the real preserving value of the Fund. while commitments operating Institute takecare annual of to inflation account into taking after return enough high a to generate we need this, to accomplish for future generations of scientists. In order Fund’s the power purchasing maintaining while Institute for the spending sustainable team’sview. is to Our provide goal along-term we invest with performance; we short-term line, don’t chase Bottom the Fund? managing in key are the objectives What comprise . together Institute Ludwig the and Centers Ludwig six The Centers. Ludwig US six at research cancer to support interests Mr. business gave his US-based Ludwig annual operating budget. Separately, Institute’s total 60% of the approximately supplies currently it and Institute, Ludwig the is to support Fund’sThe purpose sole of assets. spectrum diversified broadly and liquid amore in reinvested Fund to be the of control the under placed proceeds the and were sold over time businesses those of assets The Institute. Ludwig the support to businesses his international gifted He research. to cancer of worth his net all substantially donated Ludwig Daniel Fund? LICR the is What Ludwig’s secret weapon

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result of the word’s growing growing word’s the of result a was month last “selfie” of Oxford’s buzz-worthy choice “science”! at Merriam-Webster picked but thepublishers American year, the of word their as pickedDictionaries “selfie” publishers of the Oxford The Britishdictionaries. the of battle the was It 2013… of word top for “selfie” rivals “Science” of the year –SCIENTIST… year the of word 2014 for prediction Our education and technology. thetherapies, brain, vaccines, including climate change, new in science-related issues, interest of asurge to due be online dictionary. This could its in word the of lookups in 176% increase whopping a on based “science” picked Oxford’s US counterpart But fame. digital and usage DID YOU KNOW…

LUDWIG LINK | MARCH 2014 Required Reading Vogelstein B, Rosen A. KW, Kinzler N, Papadopoulos Y, Jiao I, C, Kinde Thoburn A, F, Boin FM, Fava Wigley LA, Casciola-Rosen AD, Skora AA, Joseph CG, Darrah E, Shah to cancer immunologic response disease scleroderma with an Association of the autoimmune print) of ahead (Epub 5 2013 December Science Ludwig Johns Hopkins Fu YX. RR, T, Weichselbaum Darga M, Beckett B, Burnette H, Liang L, Deng in mice promote antitumor immunity treatment synergistically Irradiation and anti-PD-L1 print) of ahead (Epub 2 2014 January Investigation Clinical of Journal Ludwig Chicago RS. Lo A, Ribas GV, Long N, Baren van JA, Sosman B, Chmielowski JA, Glaspy RF, Kefford MC, Kelley KB, Dahlman DB, Johnson T, R, Guo Chodon G, Moriceau RC, Koya A, Hong X, W, Kong Hugo H, Shi inhibitorBRAF therapy evolution in melanoma during Acquired resistance and clonal print) of ahead (Epub 212013 November Cancer Discovery Brussels Ludwig

Mischel PS. FB, Furnari WK, Cavenee JR, Heath HI, Kornblum PN, Rao CD, TF, James SF, Cloughesy Nelson R, J,Reed Wykosky S, Zhu M, Ohashi Yang H, A, Paucar K, J,Masui Wang K, Hwang A, Eskin G, T, Koga Gomez K, J, Visnyei Mottahedeh B, Gini DA, Nathanson EGFR DNA of extrachromosomal mutant mediated by dynamic regulation resistance therapy Targeted print) of ahead (Epub 5 2013 December Science SanLudwig Diego Filippakopoulos P. S, Knapp PE, Brennan S, Müller O, Fedorov H, C, Lingard Bountra M, Philpott B, P, Diez-Dacal Savitsky S, D, Martin Brotherton I, C, Felletar Wells S, Picaud bromodomain forwith selectivity the second transcriptional regulators BET of inhibitor an RVX-208, 3 2013 December USA Sciences of Academy National the of Proceedings Oxford Ludwig J. Cebon N, Tebbutt A, Dobrovic H, Do LJ, J,Vella F, Mariadason MC,Andrews Behren Chionh A, overcome by MEK1/2 inhibition not is carcinoma colon mutated proliferation in a KRAS- inhibitor−drivenBRAF tumor 10 2013 December Oncology Clinical of Journal Ludwig Melbourne

18 frontotemporal degeneration and ALS for therapy as foci RNA C9orf72 antisense and Targeted degradation of sense 192013 November USA Sciences of Academy National the of Proceedings B. Ren V, J,Bansal RDixon S, Selvaraj ligation and shotgun sequencing reconstruction using proximity- haplotype Whole-genome 3) 2013(Epub November 2013 December Nature Biotechnology Cook B, Oegema K, Desai A. Desai K, Oegema B, Cook R, Gassmann DK, Cheerambathur segregation ensures accurate chromosome complexesattachment betweenCrosstalk microtubule 6 2013 December Science J. DW, Ravits CF, Cleveland Bennett Yeo GW, Fu SR, XD, Vandenberg RH, Baloh MB, J,Harms Cady DP, Pizzo KR, Hutt S, Markmiller M, McAlonis-Downes JW, Artates K, Drenner M, Polymenidou Q, Zhu Y,SC, J,Sun Ling Qiu M, AT, Katz S, J,Watt Chun Jiang P, F, Liu S, HR, Rigo M, Li Sun Lagier-Tourenne C, Baughn

Sandberg R. B, D, Reinius Ramsköld Q, Deng cells gene expression in mammalian dynamic, random monoallelic reveals RNA-seq Single-cell 10 2014 January Science Stockholm Ludwig

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