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LUDWIG LINK | APRIL 2021 Photo courtesy the Roberts family His professional life was spent primarily primarily spent was life professional His to satellites. PCs from devices electronic in ubiquitous now technology, circuit integrated silicon-based of pioneer early an was He Health. Child of Institute the with merger its including tenure, his during expansion university’s the and projects successful several oversaw Derek Sir London, College University of provost twice was who engineer An 2012. in down stepping before years 14 nearly for Board the on served He COVID-19. from to complications due birthday, 89th his of shy month one 17th, February on away passed Roberts Derek Sir Member Board Institute Ludwig Former ROBERTS DEREK SIR targeted testing and developing in work his for renowned was José AstraZeneca. for development and research oncology of president vice executive was José death, his of time At the 61. was He disorder. brain degenerative a rare, disease, Creutzfeldt-Jakob from 22nd March died 2016, in Committee Advisory Scientific the leaving before years ten for staffing and strategy scientific Institute’s Ludwig the guide helped who Baselga, José Advisor Scientific Former BASELGA JOSÉ In memoriam 6 Ludwig Link Ludwig of issue 2012 November the in Derek Sir with interview an Read Association. Science British the of president elected year, was he following The education. and to engineering services for 1995 in knighted and 1988 in Empire British the of aCommander awarded was he 1980, in Engineering of Academy Royal the of and Society Royal the of a Fellow Elected activities. research Electric’s General up heading subsequently, and circuits, integrated complex electronics manufacturers—developing largest Britain’s of Plessy—one at first research, scientific industrial in children. four his and Silvia wife his by survived is He organization. the of President former a and Research Cancer for Association American the of aFellow was He therapies. cancer into understanding that of translation the and , of genesis the drives pathway signaling PI3K the of dysregulation how of his contributions to our understanding for known also was He cancer. breast against particularly treatments, cancer .

LUDWIG LINK | APRIL 2021 Switzerland at the Organization Organization the at Switzerland represented often he negotiator, trade Aformer Economics. of School London the and Lausanne of University the at educated was and Lausanne in 1923, 30, April on born was Pierre decades. two for distinction with served and 1987 in Research Cancer for Institute Ludwig the of Directors of Board the joined he banker, central and diplomat A Swiss October. in away passed Member, Board Ludwig aformer Languetin, Pierre LANGUETIN PIERRE in feeling best the is adiscovery “Making Science. Life in Prize Breakthrough the accepting when 2019, in science about most loved she what described Angelika aging. tissue and function size, cell stem between relationship the into insights yielded laboratory her in studies Other cancer. and disorders developmental to contribute dysfunctions those how demonstrated and life cellular of processes fundamental on aneuploidy, as such abnormalities, chromosomal of consequences and mechanisms underlying the on research pioneered Angelika scientist, Aprolific cancer. ovarian from October in away passed Amon Angelika investigator MIT Ludwig AMON ANGELIKA In memoriam 7 the Swiss Reinsurance Company. Company. Reinsurance Swiss the and Suisse Paribas Sandoz, including organizations, numerous of boards the on served also Pierre Institute, Ludwig to the service to his addition In 1985. in Board Executive its of chairman named was and Bank, National Swiss the of Board governing the of amember as stretch a decade-long began he 1976, In Trade Organization. Free European the and Development for Economic Cooperation and work. her about speaking Angelika of video ashort for MIT. at here Center Click Syndrome Down Alana the of Co-director named recently was and Research, Cancer Integrative for Institute Koch MIT, the of Member at Biology of aprofessor also was She Organization. Biology Molecular European the and Sciences and Arts of Academy American the Sciences, of Academy National the of a member was Angelika this.” experienced have to privileged I’m and scientists, other eureka moments are often shared with these that is science experimental of beauty The five. were you when Christmas like “It’s said. she world,” the

LUDWIG LINK | APRIL 2021 Events of prostate cancer cells even when men are resting. resting. are men when even cells cancer prostate of growth slow might exercise by induced factors immune in changes that showing study ongoing an presented University, Cowan Edith of Newton Robert speaker, One behaviors. healthier to instill seek that interventions of those and outcomes cancer in exercise physical of studies clinical covered day second The . of types certain of progression slowing on exercise of benefit significant the on studies preclinical his presented meanwhile, Jones, Lee Kettering’s Sloan Memorial models. mouse in metastasis reduces and responses immune anti-cancer tumor, improves the of vasculature the normalizes exercise that discovery lab’s his discussed Jain Rakesh investigator Harvard Ludwig session, latter the In effects. such drive might that mechanisms physiological and molecular the on asession by followed cancer, and exercise physical on epidemiology existing the covered speakers Ratcliffe, Peter Oxford’s Ludwig and Dang Chi Van Director Scientific by remarks opening After partnership. same the by organized Conference Activity –Physical Prevention Cancer virtual international, an in 2021, to 25th, 23rd February from taken was second The direction. that in step a first apublication with along 2018, in UK Research Cancer with partnership in London in convened Conference, Nutrition and Prevention ACancer policy. public into incorporation its for support and community, medical and scientific the in prevention cancer of promotion the was goals stated their among 2015, in Initiative Prevention Cancer million a$10 launched Foundation Hilton N. Conrad the and Research Cancer Ludwig When PREVENTION CANCER AND EXERCISE CONFERENCE: VIRTUAL that emerged from the meeting, was was meeting, the from emerged that

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LUDWIG LINK | APRIL 2021 News roundup News and extended survival of the mice. The The mice. the of survival extended and radiotherapy of effects the enhanced mch1N11 antibody the with blockade PS- that found researchers The mice. in tumors to delivered radiation of dose asingle after rises cells immune tumor-infiltrating live on PS of Reports Cell in published Wolchok Jedd and Budhu Sadna Taha Merghoub, researchers MSK Astudy receptors. its with interaction its through tumors in microenvironment immunosuppressive an to promote known is it where from cells, dying of membrane outer the on levels high at found mainly molecule asmall (PS) is Phosphatidylserine REVIVALIMMUNE MSK Ludwig Taha Merghoub in January found expression expression found January in

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LUDWIG LINK | APRIL 2021 News roundup News whole-genome sequencing of 5mC 5mC of sequencing whole-genome the for method efficient and effective cost- asensitive, 2019 in reported Song Chunxiao of laboratory Oxford Ludwig The (5caC). 5-carboxycytosine and (5-fC) 5-formylcytosine (5hmC), 5-hydroxymethylcytosine are others The cancer. in disordered frequently most and common most the being (5mC) 5-methylcytosine with “marks”, distinct functionally and chemically four with modified chemically is base The genome. the across expression gene of regulation the in role important an play cytosine base DNA to the made modifications epigenetic, or Chemical, TAPS MORE AND led studies Previous mice. in radiotherapy enhanced antitumor responses following and bacteria gut butyrate-producing of vancomycin decreased the abundance antibiotic The therapy. the undermines bacteria, these of byproduct a metabolic butyrate, acid fatty short-chain the how described and mice in radiotherapy with Ruminococcaceae and bugs— of families two identified They radiotherapy. of efficacy the reduce can bacteria gut certain how showed Center Medical Southwestern Texas of University Fu Yang-Xin the of and Weichselbaum Ralph Co-director Experimental Medicine astudyIn REACTION GUT Journal of Journal the in published Lachnospiraceae in January, Ludwig Ludwig January, in —that interfere interfere —that

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LUDWIG LINK | APRIL 2021 News roundup News chromosome is left behind. left is chromosome no that ensuring thereby cell, the in elsewhere not and kinetochores at generated is signal that why explain help findings The signal. wait the to generate to them delivered locally are substrates enzymatic their how and interaction, their by events phosphorylation that prime position aparticular in held kinetochore, the at constrained geometrically are Mad2 and Cdc20 how detailed team the proteins, the of one tracks that probe avisual Using Mad2. and Cdc20 proteins, two of association the by generated is checkpoint the which by mechanism the detailed colleagues and Gonzalez Lara- Pablo Desai, Arshad Diego’s San paper a January In cell. daughter to each distributed equally are chromosomes that ensuring microtubule, to a attached firmly not is cell divisionhalts if even one kinetochore that checkpoint” a“spindle by monitored segregation of chromosomes is choreographed this cells, healthy In cell. dividing the of poles to opposite each of one pull and kinetochore the called astructure at chromosome every of to acopy on latch microtubules called cables protein division, cell During STOP SIGNAL in Science in , Ludwig , Ludwig Pablo Lara-Gonzalez Diego San Ludwig Arshad Desai Ludwig San Diego San Ludwig Jennifer Guerriero Ludwig Harvard 11

deficient TNBCs. deficient BRCA- for strategy therapeutic promising a be could inhibition CSF-1R with inhibition PARP combining that suggest authors The TME. immunosuppressive less the in Tcells killer cancer-targeting of activation by primarily mediated was effect The animals. the of survival extended antibodies blocking CSF-1R and inhibitors PARP of combination a with tumors TNBC BRCA-deficient demonstrated that treating mice bearing colleagues her and Jennifer survival. to their essential is which receptor, CSF-1 the of levels high express macrophages metabolism. These immunosuppressive lipid their of reprogramming the through state immunosuppressive an into TME the in macrophages as known cells immune pushing (TME), microenvironment tumor immune-suppressive an promote also can showed, researchers the inhibitors, PARP solution. apossible offered and strategies— to such challenge a potential investigator exposed Jennifer Guerriero Cancer paper aDecember In outcomes. to improve immunotherapy with combination their examining already are researchers responses, immune tumor anti- stimulate help also can inhibitors PARP Since fleeting. often are therapy this of benefits the but inhibitors, PARP as known drugs of aclass with treated be can genes BRCA to their mutations bearing (TNBC) cancers breast Triple negative TARGET: TNBC , a team led by Ludwig Harvard Harvard Ludwig by led , ateam Nature Nature in

LUDWIG LINK | APRIL 2021 News roundup News therapies. therapies. immunological for target aprime be could receptor the suggest findings these argue researchers The mice. in disease autoimmune fatal and early to induce LXR the of copy one just of loss the Indeed, function. Treg compromises profoundly show, colleagues his and Alexander deficiency, LXR responses. immune anti-cancer from tumors protect and Tcells effector suppress (Tregs), which Tcells regulatory that its compromises loss especially and fitness, Tcell for needed is receptor the that showed Tcells normal and cells LXR of populations mixed with mice chimeric of Studies T cells. effector of activation spontaneous the by accompanied cells of T deficiency severe LXR of loss the that revealed Campbell Clarissa and Rudensky Alexander MSK’s Ludwig by led Medicine ofExperimental Journal December a In unclear. been far thus has biology Tcell in role Yet precise its responses. immune inflammatory and metabolism cholesterol and lipid of regulation the in role akey plays that receptor (LXR β Xreceptor liver The X-FACTOR IMMUNOLOGICTHE in the the in Report Definitive Brief in a mouse model leads to a leads model amouse β in gene in Tregs suffices Tregs in suffices β gene β β -deficient T -deficient ) is a nuclear anuclear ) is , a team , ateam β Ludwig MSK Ludwig Alexander Rudensky Ludwig MSK Ludwig Clarissa Campbell 12

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LUDWIG LINK | APRIL 2021 News roundup News cancer therapies. cancer as useful be could production NAD+ inhibit or respiration aerobic into cells cancer force that drugs suggest findings The offermentation. ATP: generator efficient less the employing by NAD+ of levels high maintain demonstrate, researchers the Tcells, activated and cells Cancer regeneration. mitochondrial NAD+ does so and down, slows respiration ATP.do aerobic ATP abounds, When they than more NAD+ need appears, it cells, Cancer restored. was frenzy proliferative however, their regeneration, NAD+ stimulates that adrug with treated additionally then were cells those When growth. their slowed respiration aerobic through energy, cellular of currency ATP, to make cells the cancer forcing and fermentation Inhibiting to divide. need cells all that DNA like molecules large some of synthesis to the essential achemical NAD+, of quantities large regenerate cells helps glycolysis, aerobic or fermentation, that show colleagues his and Matthew case. the is this why Cell Molecular in December in published and Heiden Vander Matthew Astudy oxygen. of starved when mainly system—use immune the of Tcells activated like ones, proliferating rapidly cells—except healthy most ATP which as and energy less much captures which fermentation, as known pathway metabolic inefficient an using sugar burn cells Cancer INEFFICIENCY ESSENTIALAN led by Ludwig MIT’s MIT’s Ludwig by led examined examined Ludwig MIT Matthew Vander Heiden Ludwig San Diego San Ludwig Don Cleveland 13

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LUDWIG LINK | APRIL 2021 News roundup News ATP, maintains the liquidity of shells and and shells of ATP, liquidity the maintains molecule the by powered activity, whose chaperones, family HSP70 to be core liquid the of components major the identified named these structures anisosomes and colleagues his and Don neurons. of nuclei the in cores liquid with shells spherical liquid into de-mixing TDP-43 protein—drives the to modifications biochemical or mutations produced by neurodegeneration-causing is TDP-43—which deficient RNA-binding reported Cleveland Don Diego’s San Ludwig by led Astudy disease. Alzheimer’s and disease Huntington’s ALS, as such diseases, neurodegenerative in seen is TDP-43 protein RNA-binding the of function of Loss CRYSTALLIQUID DYSFUNCTIONS due is This short. up come generally have protein mutated the reactivate that drugs to devise efforts cancer, human in gene mutated frequently most the is genome,” the of “guardian the called , Although p53. in defects structural some rescued trioxide— arsenic compounds—including arsenic that found and suppressor tumor p53 the of forms mutant reactivate could that drugs for ascreen performed Hematology of Institute Shanghai the of Lu Min and Lu Xin Director Oxford Ludwig by led study a theme, latter the on Building leukemia. promyelocytic acute for treatment a useful be also can it doses low in But novels. crime of device awell-worn is arsenic poison The SOLUTION STRUCTURAL online in Science in December that that December in

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LUDWIG LINK | APRIL 2021 News roundup News tumors in the mice. the in tumors of growth the inhibited significantly also it immunotherapies, blockade checkpoint with combined When cancer. colon and melanoma of models mouse in TILs of activity anti-tumor the NR stimulated with supplementation dietary notably, tumor. More the of those resembling conditions in Tcells of function and fitness mitochondrial the improved NR that showed experiments culture cell Their exhaustion. terminal from TILs rescue might it whether examined colleagues his and Ping-Chih so fitness, mitochondrial to improve others and researchers Lausanne Ludwig by shown been NRhas exhaustion. of consequence, a not acause, is showed, they This, ones. damaged remove can’t TILs the because mainly mitochondria, dysfunctional with packed are TILs exhausted that found team his and Ping-Chih state. exhausted an into TILs pushes antigens cancer by stimulation fruitless and prolonged Meanwhile, cell). the of generators more mitochondria (themaking energy by part in to compensate, processes metabolic adjust TILs tumors, in nutrients essential and oxygen of Starved TILs. the of activity anti-tumor the revive could (NR), riboside nicotinamide supplement, nutritional acommon that showed also They (TILs). lymphocytes T tumor-infiltrating enervates tumor the of microenvironment harsh the which by mechanism anovel October in reported colleagues his and Ho Ping-Chih Lausanne’s Ludwig RECHARGE TIL TIRED Nature Immunology Nature Immunology in Ludwig Lausanne Ho Ping-Chih Ludwig Chicago Ludwig 15

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LUDWIG LINK | APRIL 2021 News roundup News cancer therapies. cancer novel of development the for targeted be might that hyperactivation NRF2 on dependent tumors in avulnerability reveal results The spheroids. cancer of death the to leads GPX4 and NRF2 both inhibiting that show team her and Joan levels. high and related proteins are expressed at GPX4, ferroptosis, of suppressor critical a NRF2, lack cells when But ROS. by mediated is which ferroptosis, as known death cell programmed of atype from matrix extracellular the with contact of deprived are that spheroid the within cells cancer protects activity NRF2 survival, for As proliferation. supports mTOR by mediated Apathway outcome. each control pathways signaling distinct though cultures, spheroid of survival and proliferation both for required is hyperactivation its that showed studies Their tumors. of mimics dimensional spheroid three- models—cultured, cancer lung using experiments in survival and growth cell to cancer contributes reported colleagues and Brugge Joan Co-director Harvard Ludwig October, in published paper Cell aMolecular In (ROS). species reactive molecules reactive called oxygen highly from molecules vital other and DNA shield which systems, defense antioxidant cellular in involved genes of expression the controls that NRF2, factor, transcription the to stabilize Cancer-associated mutations are known RESCUED FROM ROS their analysis of how NRF2 NRF2 how of analysis their Ludwig Harvard Brugge Joan Maximilian Diehn Ludwig Stanford Ludwig Stanford 16 Ash Alizadeh

modified or stopped. or modified continued, be should immunotherapy anti-PD-1 whether determine quickly physicians help could DIREct-On 89%. of specificity 94% of and asensitivity with benefit clinical durable of prediction the in resulted three all Combining alone. variables three the of any of use than treatment cycle and was more precise from collected blood samples after one predicted progression-free survival accurately it studies, preliminary In well. as treatment during but before only not biomarkers of measurement noninvasive the from benefits DIREct-On Tcells. cytotoxic circulating of levels and (ctDNA) DNA tumor circulating of levels in changes tumors, in mutation of level the responses: treatment to predict biomarkers of types three incorporates method the treatment), ctDNA-On and profiling immune by Immunotherapy Response Estimation (for Durable DIREct-On, Called blockade. checkpoint PD-1 from to benefit likely are NSCLC with patients which treatment in early predict to accurately method a reported Center Cancer Kettering Sloan Memorial of Hellmann Matthew and Diehn Maximilian and Alizadeh Ash Stanford’s Ludwig by led ateam October, paper aCell In therapy. such from benefit will agents these with treated patients which identify can’t often imaging However, conventional (NSCLC). cancer lung cell non-small advanced in survival improve antibodies PD-1 inhibitors like checkpoint Immune anti- DIRECT-ON PREDICTIONS published in in published

LUDWIG LINK | APRIL 2021 News roundup News suppress anti-cancer responses. can that macrophages M2 in a decline causing and cells killer natural targeting microenvironment by activating tumor- tumor the reprogramed CAR-T4G cells the Notably, melanoma. of model mouse ina efficacy and fitness persistence, in superior were CAR-T cells their that showed and survival, and proliferation Tcell IL-15the stimulates which protein, to co-express engineered CAR-T cells (4G) “4th generation” developed also team The CAR-T cells. mouse of cultivation the (IL-2, interleukins in 15) as 7and known factors immune three of use sequential the things, other among involving, difficulty that to overcome a method Medicine ofExperimental Journal the in reported colleagues and Lanitis Evripidis Coukos, George Irving, Melita Lausanne’s Ludwig November, In tumors. in infiltrates immune inhibitory of context the in challenged not thus are CAR-T cells The system. immune an lack that mice in cells CAR-T human using evaluated preclinically been typically have therapies CAR new CAR-T cells, mouse developing with associated difficulties to technical due Meanwhile, responses. immune suppress the of microenvironments solid tumors because part in challenging, proved has tumors to solid application their cancers, blood for approved been have therapies such tumor. Though their to attack them redirects that areceptor with them engineering and Tcells blood peripheral apatient’s taking involves therapy cell (CAR)-T antigen-receptor Chimeric OFCARTS MICE

Ludwig Lausanne Evripidis Lanitis Ludwig Lausanne George Coukos Ludwig Lausanne Melita Irving 17

rate. response the improve and inhibition checkpoint to immune tumors these sensitize will ONCOS-102 by activation immune betting are researchers The 5%. than less of monotherapy inhibitor checkpoint to immune rate response a with to treat, disease a challenging is CRC Zamarin. Dmitriy MSK’s Ludwig by led and Ludwig by sponsored is study The phase. expansion an by followed levels, dosing different three with a phase dose-escalation assessing designed was trial The closed. now is which cohort, cancer ovarian the for treatment did not meet that threshold The recruitment. for open now is cohort expansion CRC the of part second the 24 and week at cohort CRC the in threshold efficacy pre-defined the met trial The unharmed. cells healthy leaving cells, cancer inside specifically engineered adenovirus that replicates an of comprised therapy cancer experimental an is ONCOS-102 abdomen. the of wall inner the lines that membrane peritoneum—the to the spread has that and platinum-resistant ovarian cancer (CRC) cancer L1 colorectal for inhibitor, aPD- durvalumab, blockade checkpoint the and ONCOS-102 virus oncolytic the of combination the evaluating 1 trial phase label open two-part, its 1of part completed tumors, solid in therapy combination for activators immune developing acompany Targovax, GOING VIRAL Clinical trials Clinical

LUDWIG LINK | APRIL 2021 along with chemotherapy to produce a to produce chemotherapy with along therapies combination need we indicate out whose results are encouraging and studies of acouple are There approaches. different from results best the get may patients which exactly to defining be going is challenge the Ithink leads. promising of alot have we yet, as cancer ovarian for immunotherapy have don’t we While of cancer? kind this for treatments immunotherapy you about near-term opportunities for are optimistic How cancer. ovarian on research of alot You’ve done patient. individual an benefitting is it whether and working is atreatment how first-hand witness and protocols clinical our technologies being implemented in to see able are we because gratifying very is work Our to them. products innovative an excellent position to deliver some in now, are we right And patients. our for products immunotherapy other and vaccines cancer developing in with work to team amazing an Ihave ours. like world the around programs translational many not are there that in Branch, Lausanne Ludwig the at here unique pretty We’re now? right work your in most you excites what about us tell you Can LUDWIG LAUSANNE OF CLINICAL TRANSLATION, A KANDALAFT LANA Q&A SSOCIATE DIRECTOR

microenvironment and its influence on a influence its and microenvironment tumor the understand we that more the now. Now right care of standard are combinations these of none But patients. for options new to some lead may drugs other with inhibition checkpoint combining and immunotherapy for partners combination viable are inhibitors PARP and Chemotherapy response. better 18

LUDWIG LINK | APRIL 2021 from my personal experience with patients. experience myfrom personal stems to cancer ovarian of my attachment part ... or sisters or mothers patients their and husbands you with interact when ballgame adifferent It’s Q&A T cells themselves are difficult to difficult are themselves T cells The receptor). cell (T TCR right the choosing antigen, right the choosing technology— the is difficulty the and develop, to difficult are they all, of First developing these therapies? about most the you worries What cancer. ovarian for cure definitive the be not will they but care, of standard the into integrated be eventually will they that hope my however. It’s cure, the not are Vaccines findings. the to validate done to be need studies larger but to go, want we that directions in us lead may that out come have data early interesting Some cancer. ovarian controlling for Tcells of importance the recognizes that strategy vaccine cancer personalized a on Branch Lausanne Ludwig the at Chiang Cheryl and Harari Alexandre here paper a Ihave and vaccines, in is interest My best. work might ones which and work therapies combination various how to understand able be we’ll more the to therapy, response patient’s out right now with my colleagues colleagues my with now right out 19

surgery followed by chemotherapy. I think Ithink chemotherapy. by followed surgery is which care, of standard the undergo who women of 85% in back bounces cancer the that such is landscape disease The treat. to challenging very it found and Coukos with George of Pennsylvania University the at Center Research Cancer Ovarian the at it on working IV. III or Istarted Stage either at advanced, quite is disease the adiagnosis, receives awoman time the by and to detect cancer tough avery it’s because killer silent the called what’s It’s you? drives that cancer ovarian about it is what challenges, these all Given doable. all are they confident I’m but to overcome, hurdles of alot We have care? of standard the of part become eventually therapies these Will patients? its to treat in-house infrastructure the have city every in and country every in hospital every Will it? with run and developed we’ve technology good the all of use make pharma Will adapt? world the will How to answer. questions big some are there therapies these developed we’ve once third, And well. as be will immunotherapies new these Ibelieve cancers, some for care of standard for approved been has therapy T-cell CAR as Just Facility. Manufacturing Cellular the and Facility Tumor Processing the facilities: manufacturing GMP two (CTE) has Therapeutics Experimental of Center the to build, years afew quite us took it While challenging. very and complex is to patients them getting and them Producing products. these infrastructure to actually manufacture the to have have you production, up to ramp order in two, Number handle.

LUDWIG LINK | APRIL 2021 ovarian cancer patients. It was a small asmall was It patients. cancer ovarian for therapies immune developing Penn at George with I worked here, to coming Prior could not do previously? you that to do you enabled it has What adifference. make hopefully and patients to our get eventually will that something on working all day, we’re the of end the at But Branch. own their run or lab own their have or PI own their notbecause member every become can development career of terms in daunting be can it Iadmit immunotherapies. novel of development and design the and immunology tumor science—primarily translational on is focus Our beat. same to the drumming all to we’re say, Ilike as Or, goal. one towards working all are we and purpose, of sense ashared has team the on everyone and organization, the for direction aspecific set has leadership The lucky. very really are we At Ludwig Lausanne? Ludwig at environment research the about stimulating most find you what us tell you Can friends. become have whom of many patients, with experience personal my from stems cancer to ovarian attachment my of part Ithink And relatives. close or mothers or sisters orhusbands other their and patients with interact you when ballgame adifferent It’s disease. this Iapproach way the and mentality my changed that Penn at Iwas when patients to exposure my been have might it But recurrence. to prevent remission in women to given be could avaccine where disease this with period waiting awatchful is there Q&A

That you can be whoever you want to want you whoever be can you That you? for provide that does perspective What international. very been has Your training now. right achieving are we what achieved have not could we resources, these Without immunotherapies. cancer for facilities manufacturing GMP two and trials clinical our to run unit investigation aclinical We have 140. of astaff with Irun which CTE, the created we Oncology, of Department CHUV’s the Within patients. the and doctors the researchers, here—the right all it have we and Europe, in centers immunotherapy largest the of one We’re all. it has that adepartment built we Lausanne, in Here everything. to outsource had and Manufacturing Practice (GMP) facility Good a have didn’t we because difficult was It vaccines. on focused operation Coukos. George Director and left, Harari, Alexandre Lausanne’s Ludwig with Lana

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LUDWIG LINK | APRIL 2021 Lana with Ludwig Lausanne Director George Coukos. George Director Lausanne Ludwig with Lana Q&A Q&A share it with others, but I have to admit to admit Ihave but others, with it share and work your about to communicate important very It’s know. Idon’t Honestly, interact? and communicate to engage, media social to use scientists for way effective/best most the is What Switzerland. or U.S. the in working are you whether science, is science line, bottom And asponge. like me around everything absorb and easily quite to adapt able I was age, ayoung such at home Ileft since But to learn. techniques new and to embrace cultures new to learn, languages new are There things. doing of way own its and mission own its has each as to adapt, have to offer. You alot has institution Each challenge. adifferent presents venue new Every attitude. right the and mindset right the is takes it All Switzerland. or U.S. the Spain, India, in you’re if matter doesn’t It are. you wherever be 21

Hanahan, I was so excited and thrilled to thrilled and excited so Iwas Hanahan, Doug saw first and 2012, in to Lausanne Icame When life. my in point a turning was That Bethesda. in Institute Cancer National the at opportunities postdoc into looking started Iimmediately do.” So must you what is This to cancer. drugs to deliver to Youdo. need you need what is this Lana, of Cancer Hallmarks The entitled Weinberg Bob and Hanahan Doug by written apaper across I came computer, to my next bench the at sitting Iwas when evening One application. areal-world see Icouldn’t but interesting, was that biology pharmaceutical in acourse started just Ihad delivery. drug pharmaceutical in PhD my on working Iwas where Wales, Cardiff, in was It of work? field your choosing to you led that astory share you Would beautiful. so but Exhausting, passion. new my It’s touring. ski and mountains the with love in fallen Ihave Switzerland, to moving since And loud. very played music— Jovi’s Bon to Jon thesis PhD entire my Iwrote life. my of part abig is Music mother’s. my than better even was said dad my that dish lamb a Lebanese mastered even have and cook good very a I’m boys. amazing two with mother a Iam Ido. But life. private no I have that think they Iknow and workaholic, a as me perceive people that aware I’m know about you? to surprised be readers our would What start. to even team good of communications a very support the need Iwould media. social using about think to even now right time the I lack

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LUDWIG LINK | APRIL 2021 is challenging as it is, and it doesn’t really really doesn’t it and is, it as challenging is science of field The women. of supportive but nothing been has leadership the where environment an in worked always Ihave that in lucky very been Ihave Again, women? to mentor helping in role your see you do How scientist? female a as experience your been has What media lately about women in science. the in discussion of alot been has There to. to run music great It’s up. pumped me gets that 80’s the from music the definitely it’s But them. playing always was dad my up, growing because oldies of to alot listen I also cool. to be Iwant to, and listening are kids my what it’s because rap French into I’m to? listen you do music of kind What music. to listen course, of and, boys the with movies of alot Iwatch And are. sports thing, my not is Opera weekends. the on alot ski we winter in and tennis of a lot play Istill Irun. when me alongside bike often will they independent, to be them Iencourage While younger. were they when did I than old, years five and 10 now are who sons, two my with connection adifferent Ihave changed. has a mother as role my where life my in astage at I’m you involved in? are activities other what hats, science many your wearing not you’re When life. my changed and me touched really that paper amazing his was it and here, is Hanahan Doug myself, to saying Ikept red. completely turned face my Iknow that him meet actually Q&A

next generation. next the inspire and to mentor is it important how reinforced and deeply me touched That acareer.” me gave you ajob, me give just didn’t you “Lana, said, and to me came day, she One industry. pharmaceutical the in works CHUV. now the at She here department our in member a key became ultimately and promotions, of anumber received years the over and me for to work came who postdoc female talented very one Ihad level. next the reach them to key helping is generation younger the Mentoring possible. lab the outside alife whether ask and like, is life my what Idid, what to achieve able was I how to know want who women young by approached often Iam to it. devote to time more Ihad wish Ioften and me, to important very is amentor as role My positions. leadership in are many and female, are employees the of 69% as represented well are CHUV, the at women Here goal. same the towards working is everyone female, or male are you whether matter in the U.S. working whether you are or Switzerland. like bottom line, And asponge. is science, science me around everything absorb and quiteadapt easily to able age, ayoung Iwas atsuch home Ileft Since 22

LUDWIG LINK | APRIL 2021 Ask a scientist a Ask on balancing your work and personal life? your personal on and work balancing your perspectiveHow changed the pandemic has MICHELLE MONJE DEISSEROTH MONJE MICHELLE level. to anew improved has to multi-task ability my and wonderful, really been has travel academic frequent from abreak to take achance and children my with time extra the But hard. been has apaper. It write or experiment an about creatively think Ican when moments un-interrupted and quiet rare those cherish and to seek day, and every accomplish Ican what of expectations my to reset commitments, to work more “no” to say learning been Ihave reality, unbalanced new To this with seems. it cope time the all time, same the at childcare 100% and work 100% doing been Ihave and medicine) academic in also is (who husband My down. shut schools and hit pandemic the when disappeared balance of system That children. four our and husband my with time good spending and for caring with clinic the and lab the in work my balance to me allowed that structure support and asystem Ihad pandemic, to the Prior Ludwig Lausanne HO PING-CHIH culture. training and research our for changes positive brings it that feel Ido ways, many in sad is pandemic this Although way. own their in goal to our heading is lab my in everyone that fact the appreciate and motivation research my sustaining to key is balance work-life that Irealize 2020, in happened reset ‘valuable’ the development of my lab After members. the shocking experience and a supporting as well as life, personal my maintaining on especially sustainable, not was mindset my that now see I meetings. scientific for frequently travel to Ihad and life, my of center the was research pandemic, to the Prior Ludwig Stanford

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LUDWIG LINK | APRIL 2021 Ask a scientist a Ask Ludwig Chicago Ludwig SEAN PITRODA personal. or professional whether enjoy, most we that lives our of aspects the prioritize can we well to how down comes balance work-life of mastery it is vital for mental and physical health and future success. learned I’ve that goal— aworthwhile just not is balance awork-life achieving that realized I’ve Ludwig Oxford ALICE NEAL focus. full my with and times separate at parent to and to work grateful very be Iwill future the In parenting. to good or research to good either conducive not is This etc. childcare, for home rushing then time in lab baby, cramming a crying shushing to whilst emails responding meeting, alab in whilst Home-schooling time. personal and work between boundaries firm having of importance the emphasized has pandemic For the me, Ludwig Oxford M MICHAEL over. no control have you that things about to worry not learned also Ihave work. of outside interests of nature indispensable the highlighted has home at time extra the whilst efficient, more being by Iexpected than more to achieve able Iam found Ihave system, shift the by limited hours With Ludwig Lausanne FRANCESCA ALFEI period. tough this in even going progress and research my keep to fight and best my do However, Iwill career. my on impact anegative have will this Ifear and missing, still is network agood build and to to conferences go possibility The disorientation. and uncertainty of sense ageneral brought has pandemic This c

CLELLAN

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LUDWIG LINK | APRIL 2021 Required reading Brugge JS. Brugge SP, T, Gygi Zhang IS, T, Harris Fujiwara R, Kaul HJ, Kuiken LM, P, Cho N, Selfors Takahashi Ferroptosis. and Proliferation of Regulation via Formation Spheroid for a Prerequisite as NRF2 Hyperactive Reveal Screens CRISPR with Models Culture 3D Epub 30 October 2020 Cell Molecular JL. Guerriero EM, Cheney AK, Mehta cancer breast associated triple-negative BRCA1- in resistance inhibitor PARP overcomes macrophages Targeting immunosuppressive 2020 December 14 Nature Cancer Ludwig Harvard W. Lin RR, T, T, Wu Weichselbaum Luo A, Culbert N, Guo G, Lan K, Ni vaccination. cancer situ in frameworks for x-ray activated Nanoscale metal-organic 2 October 2020 Science Advances RR. Weichselbaum Fu YX, JA, SP, Gilbert Pitroda SJ, Chmura K, Tatebe R, Torres L, W, Wang Zheng A, Sharma H, Y, Y, Liang Hou Zhang K, Yang radiation. antitumor effects of ionizing impairs butyrate derived interferon by gut microbiota- I type local of Suppression 2021 January 26 Medicine Experimental Journal of Chicago Ludwig

Matheson NJ, Vander Heiden MG. Heiden Vander NJ, Matheson S, Spranger CJ, Thomas CA, Lewis A, Ali A, Naamati R, BT, Do M, Ferreira Zagorulya LB, DY, Sullivan Gui Z, Li A, Luengo glycolysis. aerobic ATP to drives relative NAD+ for demand Increased print of ahead Online 22 December 2020 Cell Molecular Ludwig MIT PC. Ho N, Vannini C, Bock Tang L, PS, Liu A, JW, Zippelius YF, Locasale Jiang G, Coukos C, Jandus WC, Cheng R, F, Genolet Franco M, Rincon-Restrepo M, Gao Z, T, Xiao Chao H, Wang H, Imrichova Yu YR, exhaustion. T cell reinforce TILs CD8+ in dynamics Disturbed mitochondrial print of ahead 5Online October 2020 Nature Immunology M. Irving G, Coukos D, Dangaj P, Romero B, Seijo A, Spill P, C, Kosti G, Ronet Rota E, Lanitis coexpression. IL-15 of effects beneficial the reveals CAR-T cells murine of Optimized gene engineering 2020 November 6 Medicine Experimental Journal of Ludwig Lausanne

25 Rudensky AY. Rudensky P, Cohen AM, Intlekofer CS, Leslie Y, Pritykin M, J, Schizas Veeken der van N, Takemoto AJ, Michaels F, Marchildon C, Campbell infection. during feeding reduced to responses Tcell-intrinsic mediates FXR Epub 14 December 2020 Academy of Sciences USA National the of Proceedings AY. Rudensky R, Puerto Bou- C, Campbell AJ, Michaels activated T cells. of functionality and fitness Nuclear receptorNuclear LXR 29 December 2020 Medicine Journal of Experimental T. Merghoub JD, Wolchok CA, Barker L, Deng G, Mazo C, Liu M, O,Gigoux Henau De LF, Campesato D, Hirschhorn S, Schad R, Zappasodi K, Fitzgerald A, Gupta R, Giese S, Budhu model of melanoma. apreclinical in therapy radiation response to tumor-directed anti-tumor the enhances Targeting phosphatidylserine 2021 January 12 Reports Cell MSK Ludwig Ahmed AA, Song CX. Song AA, Ahmed M, P, J, Inoue Chen Zielińska J, Siejka- Y, Cheng Z, Liu Hu resolution. base at derivatives oxidized its and 5-methylcytosine of sequencing specific free Subtraction-free and bisulfite- 2021 January 27 Nature Communications Oxford Ludwig

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Campbell PJ, Cleveland DW. PJ, Cleveland Campbell B, Ren MH, Y, Sun Ellisman JSZ, Yu Li M, GA, Castillon R, Fang DH, Y, Kim Ly P,R, Nechemia-Arbely SF, Yaeger O,Brunner Shoshani cancer. in amplification gene of evolution Chromothripsis drives the Epub 23 December 2020 Nature DW. Cleveland E, Villa AS, Gladfelter M, Lafarga JM, Newby S, Cruz Da 3rd, JR Yates MS, Beccari D, Toprani O, Tapia S, Vazquez-Sanchez D, Singh K, Gasior S, Yu Lu H, shells. intranuclear liquid spherical anisotropic into TDP-43 free RNA- chaperones HSP70 print of ahead Online Science 2020 December 17 A Desai K; Corbett K; T; Kim P; Oegema Lara-Gonzalez at kinetochores. unattached assembly Mad2-Cdc20 catalyzes mechanism A tripartite 1 January 2021 Science Diego San Ludwig Chen SJ, Lu M. Lu SJ, Chen X, Lu SJ, ZY, Xiao YT, Wang Li YF, Yan N, Xing LL, Wu HX, Song Y, Tang YG, Liang JL, Wu S, Chen Site. Allosteric aCryptic through Mutations p53 Structural Rescues Trioxide Arsenic print of ahead Online 2020 December 7 Cell Cancer

LUDWIG LINK | APRIL 2021 Required reading Diehn M. Diehn AA, Alizadeh MD, Hellmann AM, Newman RB, Ko EL, Chen C, Yoo AJ, Plodkowski M, Das KJ, Ramchandran SK, Padda HA, JW, Wakelee T, Neal Merghoub C, YJ, Liu D, Tseng Jeon MC, Jin RF, Bonilla L, Gojenola H, Stehr D, Almanza AB, Hui CL, Liu AA, Chaudhuri CB, Steen H, Rizvi JJ, Chabon EG, Hamilton EJ, Moding MS, BY, Esfahani Nabet immune checkpoint inhibition from benefit therapeutic of identification early Noninvasive print of ahead Epub 2020 October 1 Cell Stanford Ludwig

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LUDWIG LINK | APRIL 2021 LUDWIGCANCERRESEARCH.ORG