LINK LUDWIG AUGUST 2020 1 7 | Remembering Sam Gambhir Ludwig Professor, mentor mentor Professor, Ludwig Renowned scientist, and inventor dies at 57 at dies inventor and IN THIS ISSUE IN THIS

LIFE-CHANGING SCIENCE LIFE-CHANGING section A special 21 | 21 research cancer and COVID-19 on scientist Ask a Ask

LUDWIG LINK | AUGUST 2020 The cover incorporates aslice of cover the incorporates result. The awakening social to abroader and prejudice forms. in its many in protests the provoked systemic U.S. racism has sustained against inspired which following discussions by was Floyd, the death of George activity The the inclusiveness. genuine and achievement of diversity associates with Attendees to each asked were paint or the phrase word atownhallgenerated meeting during New of York the Ludwig office. aZoom from of this “whiteboard” cover image derives The issue ON THE COVER 2

LUDWIG LINK | AUGUST 2020 LETTER Senior Vice President for Communications for President Vice Senior Rachel Reinhardt reading! Happy section. ascientist Ask special our in said they what out Find general. in care and research cancer and work own their to influence likely is pandemic the how on thoughts their to share scientists Ludwig ask we’d thought We also Committee. Advisory Scientific Institute’s Ludwig the of accomplished immunologist Bob Schreiber—a new member the about issue this in alittle learn you’ll researchers, Ludwig by won awards and honors usual the Along missed. be will He to many. mentor and teacher colleague, abeloved also was inventor, Sam inspired an and Aphysician-scientist origin. unknown of acancer from July in died Gambhir Sam Sanjiv Stanford at Professor Ludwig issue: this in news sad some have We also demand. on off and on switched be can that CAR- anew and cancer lung to detect test aurine things, other among on, items include features other Our storm. cytokine the COVID-19, of consequence deadliest the for intervention apreventive as drug pressure blood ageneric evaluate trial launched by Ludwig Johns Hopkins to researchers aclinical on abrief includes issue this in news research The pandemic. the through managing on webinars this past quarter, which shared tips and resources Insights Scientific Ludwig the on report brief a here find

planning new experiments. You’ll You’ll experiments. new planning data, preparing papers and have been hard at work, analyzing operations, Ludwig researchers lab disrupted have pandemic the Though lockdowns imposed by scientists. Ludwig are Nor away. go to COVID-19 for waiting isn’t Cancer 3 LUDWIG LINK ludwigcancerresearch.org anaging the new normal new the anaging Navigating the pandemic Gambhir Sam anjiv In memoriam benefit to human science linking or excellence scientific general or distinctions and Awards TABLE OF CONTENTS Required reading d cancer research COVID-19 on section pecial ascientist Ask warning entilatory replicas RISPR resistance of n environment number elltale switch ill research for oci odds alculated potential nnate raitorous targets cancer sting ugs read ong system warning arly econdhand sensitivity bugs elpful toilet smart ery promise of AR-T full bud the in ip prevention of n ounce oward detection early roundup News advisor scientific ew move the on People For a stellar start For astellar genome dark the For illuminating For high-impact research Diverse landscapes Diverse M S F F an A s V C A T K F C I T B A l E S H V A C A n A T A n

AUGUST 2020

3 2 2 1 1 1 2 1 1 1 1 1 18 1 1 1 1 1 1 1 1 1 4 8 9 9 5 0 0 7 4 4 4 4 2 2 9 9 9 9 8 8 6 3 3 6 6 6 5 5 5 7 7 7 1 1 1

LUDWIG LINK | AUGUST 2020 Awards distinctions and Ludwig Harvard Kornelia Polyak Ludwig Oxford Ratcliffe Peter

Ludwig Harvard Myles Brown Ludwig Harvard Alan D’Andrea Ludwig Harvard Rakesh Jain

4 innovation and progress cancer.” against significant “propelled have contributions scientific whose those on AACR the by bestowed honor an is Academy to the Election . various of progression and initiation the in play receptors cellular their and hormones steroid role the on discoveries his for Brown Myles and anemia; Fanconi drive defects such how defining for and repair, and damage DNA of field to the contributions his for D’Andrea Alan metastasis; cancer and cancer breast in heterogeneity intratumoral of role the dissecting for Korneliaimmunotherapies; Polyak and chemo- improve and vessels blood tumor normalize can therapy resistance, and how anti-angiogenic confers and tumorfuels progression microenvironment tumor the how of investigations his for recognized was Jain Rakesh researchers. Harvard Ludwig four depletion—and to its respond and oxygen sense cells how on discoveries landmark his for recognized was Ratcliffe—who Peter Sir Oxford’s Ludwig include honorees May. in The 2020 of Class (AACR) Research Cancer for Association American the of Academy the of Fellows named were scientists Ludwig Five RESEARCH HIGH-IMPACTFOR

LUDWIG LINK | AUGUST 2020 Awards distinctions and the benefit of humanity.” of benefit the for science of use and development the to encourage and science in excellence support and promote, to “recognize, is theand mission whose Commonwealth UK the in technologists and engineers storied fellowship of eminent scientists, a is Society Royal the 1660, in Founded Organization. Biology Molecular European the of amember and Pathologists of College Royal the of election by a Fellow Biology, of Society Royal the and Sciences Medical of Academy the of a Fellow Oxford, of University the at Medicine of Department Nuffield the in a Professor is and 2007 in established was it since Branch Oxford Ludwig’s directed has Xin deathcardiac and brain abnormalities. sudden including disorders, other in role their exposed has proteins those of continuing exploration Xin’s cells, cancer killing to selectively approaches new opening from Aside activity. control which proteins, of family ASPP the of characterization functional and discovery the leading for known best perhaps is She cancers. of variety awide of progression the aids mutation or inactivation whose protein suppressor atumor p53, of regulation the on work her particularly biology, cell cancer of understanding our to contributions her for Society Royal the by recognized was Xin Society. Royal the of Fellowship to the elected was Lu Xin Director Oxford Ludwig April, In EXCELLENCE SCIENTIFIC GENERAL FOR

Ludwig Oxford Xin Lu

Ludwig Harvard George Demetri 5

virtually all cancers. cancers. all virtually of subsets rare in TRK-fusions oncogenic of inhibitors recent the including , of range awide for drugs of development the influenced has work His sarcomas. other for treatments as well as GISTs, for treatments generation third and second of approval to the led research George’sblood subsequent cancers. other and fusion aPDGF-gene by driven sarcoma DFSP, for adifferent approved been also has drug the collaboration, George’s With approval. second the was GIST leukemia; myeloid chronic in ABL, BCR- oncoprotein, fusion the to inhibit developed initially was Imatinib sarcoma. (GISTs), common most the tumors stromal gastrointestinal for imatinib, therapy, targeted first the of approval to historic 2002 in led oncogene KIT mutated the of inhibitors selective of development His sarcomas. as known bone, and tissue soft the in arise that cancers of treatment contributions to our understanding and major made has George treatment. and diagnosis research, to cancer recognizes outstanding contributions Award Karnofsky the Oncology, Clinical of Society American the by bestowed Among the most prestigious honors 2020. August in meeting ASCO virtual the at Lecture Karnofsky the deliver will He April. in Award Karnofsky A. David 2020 the of recipient the named was Demetri George Co-director Harvard Ludwig TO HUMAN BENEFIT HUMAN TO SCIENCE LINKING FOR

LUDWIG LINK | AUGUST 2020 Awards distinctions and Ludwig Johns Hopkins Johns Ludwig Jonathan Dudley Ludwig Stanford Howard Chang

these cancers earlier can improve the the improve can earlier cancers these Detecting growth. tumor of stages early the in methods biopsy liquid traditional with detect to difficult is but cancers, of 90% over in present is Aneuploidy aneuploidy. or DNA, of amounts abnormal have that smears pap and urine in cells to detect away developing is Jonathan pathologist, Aboard-certified cancers. ovarian and endometrial bladder, for to screening approach anew on work his for Award Training Physician-Scientist Runyon Damon prestigious year’s this of awinner named was Dudley Jonathan researcher Hopkins Johns May,In Ludwig STARTFOR ASTELLAR their maintain and establish body the of cells how explored also has Howard cancers. of genesis to the to aging development from embryonic ranging regions influence biological phenomena how DNA regulatory sequences in these on discoveries transformative made have technologies, Howard and his colleagues these 2%. Applying remaining the of the expression the whole—control of proteins—98% no encode that genome the of expanses large the how new technologiespowerful to explore developed has lab Howard’s April. in (AAAS) Sciences and Arts of Academy American the (NAS) and Sciences of Academy National to the elected was Chang Howard Professor Stanford Ludwig ILLUMINATING GENOME FOR DARK THE 6 honors a scientist can receive. can ascientist honors highest the of one considered is NAS the to Election technology. and to science related matters on nation to the advice objective with independent, providing charged and 1863 in established was NAS The people.” virtuous and independent, afree, of happiness and honor, dignity, interest, the to advance tend may which science and art every cultivate “to seeks and excellence honors AAAS the 1780, in processes, including cancer. Established biological of array an in roles critical play and activity gene regulate that RNAs noncoding long encoding genes of family asprawling of discovery lab’s to his led that identity—work positional cytology specimens. cytology urine in DNA cell-free from cancer bladder to detect amethod creating Alizadeh Ash Diehn and Maximilian investigators Stanford Ludwig with fellowship and residency his during initiated he work for recognized was Jonathan pathology. human of field the in paper outstanding an for year each forty under pathologist to one given is award The conference. national its at Pathology of Academy Canadian and States United the from Award Castleman Benjamin year’s this received also Jonathan acure. for odds

LUDWIG LINK | AUGUST 2020 formed the basis of three biotechnology biotechnology three of basis the formed lab Sam’s in developed Technologies immunotherapies. of efficacy therapeutic the to monitor patients in activated cells immune of tracking visual the permits that one is inventions recent notable most his Among therapy. of monitoring better and cancer of detection early the for imaging molecular of methods new pioneer success—to remarkable soughtSam with great urgency—and diagnostics. cancer for use its enabled that algorithms decision the of many writing clinic, to the scans PET to bringing instrumental was Sam career, his in Early body. living the in processes molecular to visualize physics and math applying with fascination alifelong developed he where Angeles, Los California, of University the at program MD/PhD an in enrolled India, from immigrant an Sam, 19, of age the at college Finishing Detection. Early Cancer for Stanford at Center Canary the of director and co-founder also was He Stanford. at Center Diagnostics Integrated and Health Precision the of and Program Imaging Molecular the of Director and Radiology of Department the of Chair was He cancer. of detection early to the application its of apioneer and imaging molecular modern of founders the among considered was Sam colleague, and mentor abeloved and physician, and scientist 57. was Arenowned He origin. unknown of acancer from 18th July died University, Stanford at Research Cancer in Investigation Clinical for Professor Ludwig D.K. and Virginia Gambhir, Sam Sanjiv SANJIV SAM GAMBHIR In memoriam 1962-2020 statement upon his death Ludwig’s report. Highlights 2018 Research profile ( inventions life, Sam’s about more learn can You 2016. in Inventors of Academy National the and 2014, in Science of Advancement the for Association American the 2008, in Medicine of Academy National to the elected was Sam patents, of scores and papers scientific of hundreds of author An patients. cancer countless of lives the save help time, in will, and companies see page 13 page see we prepared of him for our annual annual our for him of prepared we 7 in a in passions intellectual ) and is available here

. and Peter Kim Peter and Sam Gambhir late the Chang, Howard Shapiro, Lucy Weissman, Irv Professors Ludwig Stanford with left) from (third McDermott Ed CEO Ludwig

LUDWIG LINK | AUGUST 2020 Navigating the pandemic the Navigating and the June 23rd webinar can be accessed here accessed be can webinar 23rd June the and here available is webinar 10th June the of A recording lab. to the safely to return, plans their or returning, experiences their about spoke also They environment. current the in research cancer conducting for practices best including experience, the from learned they’ve what and pandemic the by imposed lockdowns to the adapted they’ve how discussed panelists The Reinhardt. Rachel Communications for President Vice Senior Ludwig’s by moderated was discussion The Wolchok. Jedd Member MSK Ludwig and Joyce Johanna Member Lausanne Ludwig Sorger, Peter investigator and Demetri George Co-director Harvard Ludwig included Panelists patients. and staff research of safety the ensuring while research to resume best how and normal” “new the in research cancer of future the on discussion apanel was 23rd, June on held webinar, second The identified. they challenges and successes the on thoughts own his offering lockdown, the during teams remote managing on insights and experience their about Majeti Ravi investigator Stanford Ludwig and Song Chunxiao Oxford’s Ludwig interviewed be here accessed can covered he platforms and tools The meetings. virtual of conduct the for practices best on recommendations and teamwork, remote for there out technologies and tools effective most the of demonstrations) quick (and asurvey included presentation His organizations. other among Google, and Nike Festival, Film Sundance with worked has who facilitation team virtual in expert Owen Chad by presentation interactive a highly with began 10th, June broadcast webinar, first The research. scientific of disruption its with dealing and pandemic COVID-19 the through managing of issue relevant universally the on quarter past this focus its turned series webinar Insights Scientific Ludwig The MANAGING NORMAL THE NEW . In the second half of the webinar, Chad Chad webinar, the of half second the . In , an , an . , 8 Ludwig Lausanne Joyce Johanna Ludwig Harvard George Demetri Ludwig Oxford Chunxiao Song

Ludwig Stanford Majeti Ravi Ludwig MSK Ludwig Jedd Wolchok Ludwig Harvard Peter Sorger

LUDWIG LINK | AUGUST 2020 People on the move Association for Research. Cancer American the of aFellow and Sciences, of Academy National the and Sciences and Arts of Academy American the of member a is Bob papers, reviewed peer 300 than more of author An immunotherapy. cancer to personalized approaches novel developing also while tumor basic of understanding to our contributions notable to make continues Bob attack. and detection immune evade that forms into evolution their drives tumors of surveillance immune the which by process the immunoediting,” “cancer of concept the validate experimentally and to formulate on went pair The clearance. immune evade cells cancer helps signals discovered CEO, Bob and director scientific former Ludwig’s Old, Lloyd late the with Working microbes. and cells cancer to target factor IFN- immune-stimulating the that career his in early demonstrated Bob immunology, tumor modern of Center. Apioneer Cancer Siteman Comprehensive University’s Washington at Program Immunology Tumor the of Co-Leader and Programs Immunotherapy and Immunology Human for Center Bursky University Washington the of Director Immunobiology, of Division the of Director Interim the also is He Committee. Advisory Scientific Ludwig’s joined has Medicine, of School University at and Immunology Pathology Washington of Professor Distinguished Bursky M. Jane and M. Andrew the Schreiber, Robert ADVISOR SCIENTIFIC NEW A γ that the disruption of IFN- of disruption the that activates macrophages

γ

Committee Advisory Scientific Ludwig Robert Schreiber Ludwig Lausanne Johanna Joyce Johanna 9

News roundup News and beyond. Lausanne Ludwig at immunotherapies personalized highly of development the for resource invaluable an to be likely are findings detailed richly tumor.of These type each of characteristics innate the and biology unique brain’s the of interplay the by shaped are cells constituent their of states functional the and landscapes immune the of composition the that showed and TME brain the sculpt predominantly that cells immune of types the identified study Their cells. immune recruited and resident their of states functional the in differences key capture and type tumor each of landscape immune the map to comprehensively integrated then were analyses diverse These cells. immune individual of patterns expression gene global the and samples the in factors, growth and cytokines including proteins, of spectrum a profiled also They patients. from obtained samples 100 of (TME) microenvironment tumor the in cells immune of types different 14 of preferential and the locations numbers surveyed They skin. and breast lungs, the from organ to the metastasize that those and gliomas, or brain, the in arise that tumors of landscapes immune distinct the of analysis comparative asweeping reported team her and Joyce Johanna Lausanne’s Ludwig aCell In LANDSCAPES DIVERSE paper published online in May, in online published

LUDWIG LINK | AUGUST 2020 News roundup News by the Ludwig Johns Hopkins team, and and team, Hopkins Johns Ludwig the by co-founded acompany Detection, Earlier Thrive included study the in Collaborators cancers. undiagnosed for to look CancerSEEK named Hopkins Johns Ludwig at developed test ablood them gave and cancer of history or evidence no had who women 9,900 than more enrolled study The population. general the in cancers multiple to detect screening standard with combined biopsy aliquid of the evaluating feasibility study pioneering online in Science published paper April an in reported Kinzler Ken and Vogelstein Bert Co-directors and investigator Nickolas Papadopoulos Hopkins Johns Ludwig by led Researchers TOWARD EARLY DETECTION Hopkins Johns Ludwig Nickolas Papadopoulos

the results of a of results the Ludwig Johns Hopkins Johns Ludwig

removed with intent to cure. surgically be could twelve and scanning, PET-CT diagnostic by localized were cancers identified Most 31%. of sensitivity a with cancers, ovarian and kidney thyroid, as such exist, not do tests screening which for cancers seven detected also test blood The 47% to 71%. from tumors lung and colon breast, detecting of the blood test improved the sensitivity spread far. Adding screening standard to hadn’t 65% which of malignancies, identifying 26 previously undetected screening, to traditional added when detected cancers of number the doubled than more biopsy liquid The System. Health Geisinger the at researchers 10 Ludwig Johns Hopkins Johns Ludwig Ken Kinzler

LUDWIG LINK | AUGUST 2020 News roundup News hospital admission. hospital to prevent stages disease earliest the in patients COVID-19 hospitalized to non- trials clinical extending on focused currently is team the rising, numbers case With COVID-19. with patients hospitalized in storms cytokine against intervention preventive early, an as prazosin alpha-blocker the to test Chetan by led trial aclinical for Administration Drug and Food U.S. the from approval received researchers May, the In ventilators. on while dying of risk lower 56% and ventilation requiring of risk lower a35% had blockers alpha- taking were and ARD had who patients found They hadn’t. who to men outcomes their compared and reasons other for alpha-blockers taking been had and causes multiple from ARD had who 13,125 men on data clinical examined retrospectively Vogelstein Joshua and Athey Susan including team extended an analysis arecent In mice. in release cytokine blockers) could impede self-amplifying cycles of as alpha-1 adrenergic receptor antagonists (alpha- known drugs hypertension that showed study That storms. cytokine precipitate that cells, immune the molecular mechanisms, mediatedNature by in detailed had Zhou Shibin and Staedtke Verena Vogelstein, Bert by led researchers Hopkins Johns Ludwig 2018, In (ARD). distress respiratory acute with ventilators on ICU the in up wind patients COVID-19 reason main the is storm cytokine the inflammation, systemic runaway, causes that response immune acascading by Induced mortality. COVID-19 of cause leading syndrome—a storm cytokine to prevent prazosin named drug a employing trial hypertension a for arationale presented Hopkins Johns Ludwig from Konig Maximilian and Bettegowda Chetan by led researchers of ateam April, in Investigation aletter In PREVENTION OUNCE OF AN Journal of Clinical ofClinical Journal the in published on arXiv on , 11 Ludwig Johns Hopkins Johns Ludwig Shibin Zhou Hopkins Johns Ludwig Bert Vogelstein Hopkins Johns Ludwig Bettegowda Chetan

Ludwig Johns Hopkins Johns Ludwig Verena Staedtke Hopkins Johns Ludwig Maximilian Konig

LUDWIG LINK | AUGUST 2020 News roundup News Ludwig MIT Ludwig Stanford Crystal Mackall Bhatia Sangeeta

a surface protein on ATRT cells known known ATRT on cells protein a surface to target engineered were CAR-T cells eliminated in the mice. tumors The virtually ATRT that to treat therapy cell T(CAR-T) receptor antigen achimeric of colleagues reported their development and Mackall Crystal Stanford’s Ludwig Medicine aNature In months. 17 about only is this cancer, even with treatment, for survival Median toddlers. in seen with brain tumors, and most often children of 10% than fewer in found cord spinal and brain the of tumors aggressive and rare (ATRT) are tumors teratoid/rhabdoid Atypical A CAR-T OF PROMISE FULL proteases preferentially expressed by identified colleagues her and Sangeeta urine. in detected easily be can that biomarkers This releases tumors. associatedenzymes with various protease by cut specifically are which proteinshort fragments, or peptides, with coated are that lab Sangeeta’s in developed nanoparticles on relies test The accurately. so does and mice, in stages earliest its in cancer lung captures that test urine asimple describe team her and Bhatia Sangeeta MIT’s Ludwig Science in Translationalpaper Medicine April an In early. caught they’re when curable more far are cancers Lung A NIP IN THE BUD paper published in April, April, in published 12 , goes well—later in kids with ATRT. with kids in well—later goes all and—if cancer brain the with patients adult in year, first next beginning CAR-T the of cells trials clinical to conduct plan researchers The injection. intravenous than cells CAR-T fewer times 10 about required it because inflammation brain dangerous curtailed approach The vessel. ablood into cells the administering than effective more and safer was mice of brain the bathes that fluid cerebrospinal the into CAR-Tthe cells Infusing growth. its drives and cancer this by expressed abundantly is found team her and Crystal which B7-H3, as technology. new this on avideo to watch here Click scans. CT than better or well as least at cancer detected sensors The 5weeks. at mouse model, tumors could be detected other the In size. in millimeters cubic 2.8 about only were tumors the when growth, tumor of onset the 7.5 as after weeks early as models mouse the of one in tumors detected accurately test urine Their tumors. lung of types different two of one develop to spontaneously engineered models mouse of airways the into sensors the inserted then They peptides. target their with coated nanoparticles 14 of apanel created and cells cancer lung

LUDWIG LINK | AUGUST 2020 News roundup News among other things, help direct the the direct help things, other among andprecursors dendritic cells which, Treg of co-cultures in effects such for metabolism bacterial by produced acids bile of aspectrum screened team his and Alexander cancers. colorectal of driver major a inflammation, intestinal chronic (Tregs) dampen help Tcells regulatory generated, or “peripheral”, locally Such inflammation. and reactions autoimmune suppress that cells T cells—immune generationboosts of the local regulatory intestines, the in bacteria commensal friendly, by made acids bile of metabolite Nature in published and Rudensky Alexander Director MSK Ludwig by led A study BUGS HELPFUL consistencies abnormal identify that can computationally by analyzed algorithms and video on recorded are urine and Stool or urologic cancers. syndrome some diseases, such as bowel irritable of those including urine, and stool in markers disease of arange to detect tests dipstick and sensors pressure and motion cameras, uses that toilet asmart designed colleagues his and Sam answer. an with up 18—came July cancer from died who University, Stanford at Investigation Clinical for Professor Ludwig D.K. and Virginia Gambhir—the Sam by led Ateam toilet? asmart not watches—why smart have We already VERY SMART TOILET reported in April that isoDCA, a isoDCA, that April in cancer through dietary intervention. dietary through cancer colon to prevent efforts for implications has discovery The capability. this to lack tweaked bacteria same the with colonized those than intestines Tregs their in peripheral more many had isoDCA make tocolonized with engineered bacteria mice that showed also team his and Tregs.generation of peripheral Alexander the drive they which in state inflammatory anti- an into cells dendritic pushes This (FXR). Xreceptor farnesoid the cells, dendritic in sensor acid a bile by issued signals the opposes intestine, human the in abundant relatively is which isoDCA, that showed Tregs. of They generation and has garnered much media attention. media much garnered has and Naturein Biomedical Engineering described first was technology The toilet. asmart such using with comfortable somewhat least at were 52% least at that found participants prospective 300 of a survey and participants, 21 on tested been has later. far, toilet So the examine intelligence—to artificial an doctors—or for system acloud-based in stored is data All users. to individual results link prints” “anal unique of identification photographic the and reader fingerprint a with equipped lever Aflush biomarkers. ten analyze and detect currently meanwhile, tests, dipstick The flows. and 13 in April, April, in

Ludwig Stanford Sam Ghambir (1962–2020) Ludwig MSK Ludwig Alexander Rudensky

LUDWIG LINK | AUGUST 2020 News roundup News for BET/MEK-targeting therapy. BET/MEK-targeting for eligible patients to stratify used be might that biomarker a identifies study the tumors, lung driven KRAS many to treating approach novel potentially a defining from Aside tumors. the in death cell triggering and replication DNA inhibiting by effects their exert drugs these that showed team her and Karen tumors. KRAS-mutant over-expressing HOXC10 bearing mice in inhibitors BET and to MEK sensitivity conferred genes, PRC2 in defects, those that demonstrated studies Their defects. gene unappreciated, to other, far due so HOXC10 named aprotein of levels high express tumors lung such half about that found They cells. constituent their in proteins other target that therapies of to acombination responsive be might tumors NSCLC KRAS-mutant many that Karen Cichowski and colleagues reported Cancer Cell paper April an In growth. cancer of driver this target that drugs to devise difficult proved far so has it NSCLCs, in common are mutations KRAS While cancer. lung of subtype common most the (NSCLC) is cancer lung cell Non-small SENSITIVITY SECONDHAND , Ludwig Harvard investigator investigator Harvard , Ludwig in in Ludwig Harvard Karen Cichowski Maximilian Diehn Ludwig Stanford Ludwig Stanford 14 Ash Alizadeh

in Nature in paper aMarch in detailed was method The trials. clinical scale large in muster passes NSCLCs each year—providing, of course, it thousands of additional early-stage to detect scans CT with combined be could Lung-CliP use, of ease its Given positives. false fewer generates Lung-CliP Although CT are scans more sensitive, NSCLCs. stage early of 70% and 40% between detect can showed they that plasma) in likelihood cancer (for lung CLiP approach named Lung- learning-based amachine developed researchers the ctDNA, of features molecular other with capability that Integrating cells. cancer from come not does that DNA circulating of pool larger far the in found mutations such circulating tumor DNA (ctDNA) from in mutations NSCLC-related genuine devised a method to differentiate colleagues their and Ash Max, tumors. by blood the into shed DNA of bits rare extremely analyzing by NSCLC detects that test ablood developed Alizadeh Ash and Diehn Maximilian researchers Stanford Ludwig by led ateam challenges, these address To difficulties. access and done them to get reluctance including reasons, of avariety for scans the receive not do currently people high-risk most Further, positives. false many generates gold of standard screening, the CT scan, promptly treated. Trouble is the current and organs to other spread they before caught they’re if cured be can worldwide, death cancer of cause leading the (NSCLCs), cancers lung cell Non-small SYSTEM EARLY WARNING .

LUDWIG LINK | AUGUST 2020 News roundup News cells and the hepatitis B virus. Bvirus. hepatitis the and cells stem embryonic on use its demonstrate sequencinglong-read applications and TAPS for of adaptation their describe colleagues his and Chunxiao March, in new paper new a In DNA. tumor circulating including potentially samples, tiny vanishingly even on marks epigenetic sequencing sequencing. This permits its use in such for standard prevalent the than efficient more far and cheaper gentler, is named launched startup arecently- of heart the at now method, The new5-hydroxymethylcytosine. and 5-methylcytosine modifications epigenetic the of detection the for pyridine borane sequencing) method TAPS (Tet-assisted the published groups Schuster-Böckler’s Benjamin and Song’s Chunxiao Oxford’s Ludwig 2019, In cancer. of especially biological processes, array an in role acritical play that to DNA modifications epigenetic, or chemical, have complicated the sequencing of challenges Similar bases. of sequences when those encode strands repeating especially difficult, prove sometimes sequences into the full sequence can short of assembly computational the But profiling. genomic revolutionized and made DNA sequencing much cheaper then computationally reassembled—has and sequenced are length in bases 300 about strands DNA which sequencing—in short-read of optimization The READ LONG A published in Genome in Biology published Base Genomics

, Ludwig Oxford Benjamin Schuster-Böckler Ludwig Oxford Chunxiao Song Ralph Weichselbaum Ludwig Ludwig 15

for multiple tumor types. tumor multiple for atreatment as trials clinical in evaluated being now is which immunotherapy, anti-CD47 of efficacy the broadening for implications significant have could finding The effect. the eliminated antibiotics with removal Their immunotherapy. anti-CD47 stimulated responses to subsequent they where tumors, in accumulation preferential to their led to mice Bifidobacteria of administration Systemic interferons. as known factors stimulating named STING, which activates immune- cells dendritic in aprotein of signaling the boosts presence intratumoral their that show colleagues and Yang-Xin antitumor immune responses. Ralph, activate help that system immune the of sentinels cells, dendritic through wonder this work out, turns it bacteria, The colleagues). his and Weissman Irv Stanford’s Ludwig by developed first therapy (an experimental immunotherapy to anti-CD47 responses stimulate can it where tumors, in accumulates Bifidobacterium gut, the of denizen one that found researchers The well. as directly more immunotherapy aid can they that reported Center Medical Southwestern Texas of University FuYang-Xin the of and Weichselbaum Ralph Chicago’s Medicine paper aMarch In immunotherapy. to cancer responses patient influence significantly capacity, that in can, and system immune the regulate help bacteria gut Commensal CANCER STING BUGS Journal of Experimental ofExperimental Journal the in , a research team led by Ludwig Ludwig by led team , aresearch , also preferentially preferentially , also

LUDWIG LINK | AUGUST 2020 News roundup News relatively large numbers in pancreatic of these cells, ILC2s, were present in asubtype that noticed colleagues and Taha resides. it where tissues in immunity and inflammation regulate helps which (ILC), cell lymphoid innate the candidate: such one reported Balachandran Vinod physician-scientist cancer pancreatic and Taha Merghoub MSK’s Ludwig by February a In tumors. to eliminate harnessed additionally be might that cells immune other of avariety targeting therefore . Researchers are the of Tcells by tumors on attack an checkpoint blockade, which unleashes to respond cancers all of 20% about Only INNATE POTENTIAL Tregs intratumoral that discovered They side effects. autoimmune inducing model to boost immunotherapy without amouse in disrupted selectively be could and tumors in reside Tregsby that engaged exclusively is found, team his and Ping-Chih mechanism, The acidity. the with to deal metabolism their adapt immune responses and autoimmunity, suppress (Tregs), which Tcells regulatory Immunology paper aFebruary in reported colleagues and Ho Ping-Chih Lausanne’s Ludwig to survive. metabolism their to adapt cells resident forces This nutrients. vital and oxygen of starved and acidic often are tumors of cores The TARGETS TRAITOROUS paper a novel mechanism by which which by mechanism anovel in Nature , a team led led , ateam Nature Nature in forms of treatment. of forms all resisted stubbornly has that a cancer potential combination for immunotherapy a mice—identifying the in rejection tumor boosted dramatically immunotherapy IL-33 anti-PD-1 and combining that showed team their and Taha, Vinod cells. immune other and Tcells of activation the on brake a like acts that aprotein PD-1, of levels higher to express them prompted also it But tumors. on attack ILC2 the boosted IL-33 named factor immune an that PDAC then demonstrated in mouse models of researchers The longer. to live tend tumors their in cells these of more with patients ductal adenocarcinomas (PDACs) and that therapy. cancer apotential into findings these to translate working now is lab Ping-Chih’s cells. cancer on attack cell aT stimulates which immunotherapy, PD-1 anti- of effects the Tregs) boosted and intratumoral Tregs (though not other of decimation the in resulted to CD36 antibody an with tumors cells. Likewise, treating mice bearing themitochondria, power of generators their in adecline by driven apoptosis, as known suicide cell of Tregs aform intratumoral in induced deficiency CD36 import. lipid in involved areceptor CD36, lipid uptake and metabolism—particularly in involved genes of levels high express 16 Ludwig Lausanne Ho Ping-Chih Ludwig MSK Ludwig Taha Merghoub

LUDWIG LINK | AUGUST 2020 News roundup News pressure drugs. are normalized by treatment with blood stromata their when responsive more to be likely are meanwhile, types, tumor Other sequentially. given are drugs two immunotherapyblockade when the blood vessels improve checkpoint to normalize drugs antiangiogenic dose low- tumors, certain for that example, for predicts, model The suggestions. helpful some made also It studies. experimental of to results compared when well fared predictions Its immunotherapy. influence might interventions drug various how and whether predicts and TME the in cells noncancerous other and immune and factors molecular vessels, blood cells, complex interactions cancer between captures uniquely, model, The outcomes. treatment affect might interventions such how predicts that model mathematical ofSciences Academy National of the reported Cyprus of University the at acolleague and Rakesh by led ateam February, In immunotherapy. and chemotherapy to both responses improve can TME the stroma—of the tissue— supportive the noncancerous alter or vessels blood dysfunctional the normalize that drugs that demonstrated example, for has, Jain Rakesh researcher Harvard Ludwig days. these research feverish of asubject is immunotherapies existing of efficacy the broaden and to improve (TME) microenvironment tumor the of dysfunctions and conditions harsh the Tweaking CALCULATED ODDS in the Proceedings the in a Ludwig Harvard Rakesh Jain Sandro Santagata Sandro Ludwig Harvard

17

cell during proteotoxic stress. proteotoxic during cell a of fate the determines states different in foci HSF1-bearing of balance dynamic the suggest researchers The death. cell to leads which expression, chaperone reducing and HSF1 immobilizing gels, into transform foci the stress, prolonged During survival. cell tumor and activity HSF1 promotes what is formation their than rather foci of dissolution the that discovered colleagues his and Sandro integrated suite of imaging technologies, an Using not. do that those from stress proteotoxic survive that cells tumor in disposition differentiateswhat HSF1 explored Santagata Sandro by led Biology paper aFebruary In chaperones. of activation the for proxy a to be taken been has presence their and cells cancer out stressed of nucleus the within bodies” “stress as known foci in accumulates HSF1 chaperones. as known proteins stress-response of production the controls which (HSF1), 1 factor heat-shock expression, gene of regulator amaster activating permanently by stress such with cope cells Cancer stress. proteotoxic to as referred collectively that’s proteins of degradation and management folding, proper production, the in adysfunction cause thing, one for can, It cells. for stressful quite be can proliferation Ceaseless FOCI FOR RESEARCH , researchers at Ludwig Harvard Harvard Ludwig at , researchers Nature Cell Cell Nature in

LUDWIG LINK | AUGUST 2020 News roundup News CAR for clinical use. clinical for CAR STOP- their adapting now are researchers The immunotherapies. to cellular control of alayer to add design structure-based of potential the highlights system The restoredmolecule—and upon its removal. disruptive small the by off switched be can activation the But to antigen. response in CAR-T cells host their activate chains spontaneously associate and can two the interface, to the Due chain. asecond CAR-T the cell—on activates functionally part—which signaling T-cell the and chain one on CAR the of part binding tumor-antigen the placed that (CAR) design receptor antigen chimeric anovel into incorporated then were proteins The molecule. small a specific by dissociated however, be can, interface This binds. it which to scaffold modified arationally other the and natural, one proteins: human two between interface astrong devised researchers the design, computational structure-based By exhaustion. CAR-T cell and responses immune runaway dangerous to prevent demand on off and on switched be can Biotechnology Nature of issue February the in CAR) (STOP- receptor antigen chimeric novel reported Lausanne, the École Polytechnique Fédérale de of Correia Bruno colleague their with together Irving, Melita and Coukos George Director Lausanne’s Ludwig by led A team KILL SWITCH . The STOP-CAR system system STOP-CAR . The the design of a of design the Ludwig Lausanne Melita Irving Ludwig Lausanne George Coukos Ludwig Stanford Aaron Newman 18

future drug development.future drug for target aprime to be seems that marker novel one least at and cancer breast triple-negative of markers known several identified CytoTRACE tumors, such in cells stem-like on in homing In treat. to difficult notoriously is which cancer, breast negative to triple CytoTRACE applied colleagues his and Aaron gene. per copies RNA of number the and cell a by expressed genes of number the on based that’s CytoTRACE named algorithm an create expression—to gene during DNA by encoded information carries which RNA— of profiling single-cell and insight that applied then They to be. likely is cell that stem-like more and differentiated less the expressed, genes more the cell: that of state developmental the with expressed by a cell reliably correlates genes of number the that confirmed first They tumors. in counterparts their and tissues healthy in cells stem to identify way elegant an reported Newman Aaron by led investigators Stanford Ludwig paper aJanuary In cells. stem-like such target must drugs then, acancer, out To snuff truly metastases. seed and malignancies drive typically cells tumor of subset rare arelatively Only equal. created are cells cancer all Not TELLTALE NUMBER in Science in ,

LUDWIG LINK | AUGUST 2020 News roundup News immunotherapy and novel TRKis. TRKis. novel and immunotherapy of acombination include could These strategies to treat resistant disease. novel suggest and to TRKis resistance of mechanisms define help findings Their macrophages. and Tcells cytotoxic intratumoral in increase a significant the including tumor microenvironment, of profile cell immune infiltrating the in changes KRAS-induced of activation the how described also researchers The and consequent tumor progression. pathway transduction signal targeted the of to reactivation led that gene KRAS the in mutation a gain-of-function identified They tumors. patient’s the in resistance drug of evolution the analyzed colleagues their and George Sandro, generation DNA sequencing methods, next- and Harvard, Ludwig at developed system imaging spatial amultiplex Using selitrectinib. TRKi, a second-generation subsequent response when treated with disease progression occurred with TRKi, afirst-generation larotrectinib, to response major initial an After gene. NTRK1 the of fusion genomic chimeric a harbored cancer the that revealed sarcoma the of Analysis pelvis. the in originated that sarcoma ametastatic with diagnosed apatient in (TRKi) inhibitors to TRK-fusion resistance of mechanism(s) Precision Oncology paper aFebruary in reported Demetri George and Santagata Sandro Harvard’s Ludwig by led A team RESISTANCEOF ENVIRONMENT AN their analyses of the the of analyses their JCO JCO in

Ludwig Harvard George Demetri Ludwig Harvard Santagata Sandro Ludwig San Diego San Ludwig 19 Frank Furnari

tissues, such as the pancreas and lung. lung. and pancreas the as such tissues, other in tumors to model approach their using also They’re tumors. brain pediatric and adult in mutations other test and drugs to screen model their to use plan colleagues his and Frank resistance. drug of development and evolution tumor’s the of tracing the enabled also models The tumors. patient-derived of traits other and heterogeneity common cellular the replicated faithfully mice, other into re-engrafted when that, tumors GBM to authentic rise gave iPSCs engineered the mice, of brains the into engrafted When GBM. of drivers genetic known to replicate editing) gene directed for (a method CRISPR using engineered tissues— of to anumber rise give can (iPSC)—which cells stem pluripotent induced human from developed is model The limitation. this addresses that (GBM) glioblastoma cancer brain the for model engineered genetically anew of evaluation and construction their describe colleagues and Furnari Frank Diego’s Communications Nature aJanuary In animals. in time over evolve and spontaneously arise that tumors of complexity microenvironmental and the cellular replicate authentically not do they that is cancer of models many with trouble The CRISPR REPLICAS CRISPR paper , Ludwig San San , Ludwig

LUDWIG LINK | AUGUST 2020 News roundup News significantly compromises the hypoxic hypoxic the compromises significantly PT2385 inhibitor the that January in Journal of Clinical Investigation a in reported They oxygen. to low responses physiological ordinary how one HIF-2 one how explored Ratcliffe Peter and Bishop Tammie Oxford’s Ludwig development. HIF-2 cancer drugs targeting HIF—particularly microenvironments, experimental and hypoxic have typically which tumors, of avariety in activated highly also They’re starvation. to oxygen adaptation cell’s the in role acentral play that expression gene of regulators master (HIFs) are factors Hypoxia-inducible VENTILATORY WARNING Ludwig Oxford Tammie Bishop α —are well along in clinical clinical in along well —are

α -inhibitor affects -inhibitor affects Ludwig Oxford Ratcliffe Peter paper paper

altitudes. high relatively at living those or disorders, respiratory co-occurring with patients to treat HIF-2 inhibition using in caution for aneed suggests argue, they this, All directly through its effects on HIF-2 on effects its through directly but PT2385 of effect coincidental some by not induced they’re suggest effects these of biochemistry the of analysis adaptive Their responses. physiological trigger and blood the in dioxide carbon and oxygen of levels the sense which bodies, carotid in cells of proliferation the inhibits also drug The environments. oxygen low in rate breathing boosts normally which response, ventilatory 20 α .

LUDWIG LINK | AUGUST 2020 Working-from-home edition: Ask a scientist about C edition: scientist a about Ask Working-from-home research going forward. going research cancer on focus coordinated more and agreater stimulate hopefully will which challenge, acute an around coalesce to possible is it that demonstrated has pandemic The population. aging an with especially time, over world to the threat bigger amuch is Cancer inthe future? research of cancer to focus the or planning conduct, generally that might apply from the COVID-19 have you lessons learned pandemic What Rakesh Jain Sean Fanning GEOFFREY GREENE GEOFFREY Ludwig Chicago Ludwig

Johanna Joyce Geoffrey Greene 21 the pandemic is over. is pandemic the after to keep like Iwould that practice a and rewarding, very been has This experiments. troubleshooting on focus just than rather project my of picture big the on to reflect time me given has lab the in to work able being Not OVID Ludwig Johns Hopkins Emily H.Hsiue -19 research cancer and EMILY HSIUE H.

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask together’. this in all are ‘we pandemic: COVID-19 the from lesson best the learned have will we crises, unforeseen facing investigators to support future the in available remain If such measures resource-sharing. extend tenure clocks and increase should implement bridge funding, research,cancer academic institutions in generation’ To a‘lost avoid freezes. hiring and funding in shortfalls time, research to disrupted are investigators career early vulnerable especially how underscored has pandemic COVID-19 The many more over the long run. long the over more many kills Cancer glaring. is preparedness of lack the and speaking, relatively time, of period ashort in die can patients because attention gets COVID-19 underfunded. researchCancer is dangerously findings. of “ownership” protecting than rather solutions finding on focus people as science in teamwork of embrace an and resources of marshalling alarge witnessed have We change. transformational bring can urgency collective of asense research: cancer to future apply could that A lesson KABRAJI SHEHERYAR K. RALPH WEICHSELBAUM RALPH Ludwig Lausanne Ludwig Chicago Ludwig Ludwig Harvard IAN MARTEN

22 treatment. cancer of outcome the improve can blockers angiotensin how of models math this interaction—based on our previous for models mathematical developing also We are database. available the using patients these in blockers angiotensin of role the examining are we hypertensive, are patients COVID-19 and patients cancer many and COVID-19, from death and outcomes severe of risk greater at are patients cancer that Given order is implemented. stay-at-home another case in lab, the of outside done be may that approaches other and computational incorporating in interested more now I’m important. be will them in engage we how and pursue we projects the in flexible Being research groups. to resources and funding adequate treatment. Doing so requires ensuring and progression cancer of understanding the in problems large to tackle together working groups and solidarity of importance the stresses it I believe Ludwig Chicago Ludwig Chicago Ludwig Ludwig Harvard SEAN FANNING SEAN JASON BUGNO RAKESH JAIN

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask priority. sole our as care patient to advance way open atruly in collaborate and together come can absolutely we this, as immense as achallenge with faced when that is by redirecting their research programs to COVID-19 responded world the around scientists of thousands many rapidly how from came that message clear the I think strategically. more future the for plan and thoroughly more data or literature pertinent the review and back to step time for allows pandemic The moment. the of details the in lost get we Often, hypotheses. to test trainees by attended being trees to the attention pay but forest, the or questions, big the on Ifocus director, alab As back. step this taking of value the by struck been I’ve me. of front in experiment the of urgency and immediacy the in lost to get easy it’s atrainee, As work. our synthesize and analyze think, and to stop but choice no us given has pandemic The Ludwig Scientific Director Scientific Ludwig Ludwig Lausanne JOHANNA JOYCE JOHANNA ADAM WOLPAW Ludwig Wistar CHI VAN CHI DANG

23 research as well.research non-COVID in collaboration scientific global for model enticing an present could discourse scientific of extent the research is being shared publicly and new which with speed The angles. different many from problem same the about thinking and to COVID attention their of some least at refocusing been have researchers many as collaboration, This has brought about unprecedented remotely. to working shifted and another one from distancing physically been have country the across researchers as a halt to work lab experimental related COVID non- most brought has pandemic This related research in the future. conduct even more streamlined cancer- to lessons these to use able to be hope I responsibility. shared of asense and data and efforts to sharing comes it when towillingness collaborate, transparency widespread the is pandemic COVID-19 the of aspects striking most the of One fail. not must we answers: for community scientific to the looking is public The humanity. of progress and health the in science of importance the demonstrate to researchers for opportunity an is However, this pandemic. this from lessons to learn early too still is it I think FRANCESCO BOCCELLATO FRANCESCO CHETAN BETTEGOWDA Ludwig Johns Hopkins MICHAL CASPI TAL CASPI MICHAL Ludwig Stanford Ludwig Oxford Ludwig

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask we can pivot to open ones. to open pivot can we unpredictable, the by closed are doors as So astrength. into focus of alack turning interests, research many fostering of necessity the is taken I’ve lesson The into. years invested you’ve adirection abandon simply to difficult it’s yet research, in flexibility for need the highlights COVID-19 SPENCER S. WATSON Ludwig Lausanne

24 NIH funded labs. NIH funded in vaccines and treatments to test used be cannot it yet ARDS, gets and infected successfully is mice SCID in lung fetal human shows research COVID-19 Recent therapies. antibody trial clinical phase late now are which research, tissue fetal from came blockers and inhibitors checkpoint macrophage of discovery the as well as cells, stem leukemia and SC CNS and HSC of Discovery ban. the included treatment and research COVID-19 for supplements extra the and research in tissues fetal of use the banned HHS For example, science. of out politics to keep employees its and government US the on count We can’t Ludwig Stanford IRV WEISSMAN

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask emergency passed? has this after long nimbler research, cancer including cancer research more efficient and effective. and efficient more research cancer future make can practices best these adopted, widely and continued If industry. and government cooperation academia, between enhanced and worldwide, data and samples patient have asked clear research questions, shared Scientists relevant. and focused rapid, been has pandemic COVID-19 the during output Research science, medical make pandemic the coronavirus Will Sheheryar K.Kabraji Sheheryar Ralph Weichselbaum KABRAJI SHEHERYAR K. Ludwig Harvard Michal Caspi Tal Francesco Boccellato 25 interdisciplinary in the future. interdisciplinary more science make will this that hope I and fields, unrelated were thought we to what translate can knowledge our how recognized We’ve COVID-19. on expertise their refocus community biomedical the of segments huge watch to remarkable been has It so. I hope Adam Wolpaw

ADAM WOLPAW Ludwig Wistar

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask individuals. of glorification the for than rather good public the for problems cancer challenging most the of some to solve effort acommunal of form the in come will nimbleness perhaps and science, team for need the exposes pandemic The research. cancer in happening that see clearly don’t However, I specialties. medical some in could it perhaps and nice, be would That so. think I don’t thinking. of way that to sustain need We priorities. research and funding about decisions make we which in ways alter to policies our to adjust how of example and stimulus unanticipated and powerful a is pandemic the but ways, old into back fall just will we that cynical to be easy is It are maintained. to coronavirus due collaboration forced the by made already connections the and together, to work departments across Yes—people will be more willing to reach Ludwig Scientific Director Scientific Ludwig RALPH WEICHSELBAUM RALPH GEOFFREY GREENE GEOFFREY Ludwig Lausanne Ludwig Chicago Ludwig Chicago Ludwig Chicago Ludwig JASON BUGNO CHI VAN CHI DANG IAN MARTEN

26 benefitcancer research. ultimately may that and support funding such of increase even and continuation for need the reinforced pandemic The investments. private and funding federal on both relies Medical science including research cancer maintained. be can this that Ihope swiftly. more approved them to get possible is It simply. more protocols to design possible is It to conduct. easier be may trials clinical So shipped. be can medications that and online, monitored be can patients that and omitted, be can tests blood many that learned We have ideas. testing to start excited Iam and immunology, and virology of understanding my increased significantly has COVID-19 impact. significant make could we where storms), (i.e., cytokine COVID-19 and cancer the between overlap of areas are There so. I hope Ludwig Johns Hopkins GERBURG WULF GERBURG Ludwig Chicago Ludwig Ludwig Harvard Harvard Ludwig SEAN FANNING SEAN PAUL SURMAN

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask and translation. discovery to expedite ways find and norms historical re-evaluate institutions and emergency researchers cancer passes, the as that, Ihope barriers, conventional down break that workflows establishing of benefits the sees community scientific the As pandemic. this in a difference making of goal shared the towards can they as fast as and hard as working from and colleagues many collaborators benefited Ihave SARS-CoV-2. defeating goal: one on to focus community scientific entire the galvanized has pandemic The scientific disciplines. respective our on to focus return we that important is it COVID-19, after thus, and diversity its in resides science medical of response. I believe the witnessed agility attentionwidespread or emergency this receive to ever unlikely is research making research nimbler. Cancer platforms technological dedicated and programs financing fast bureaucracy, in shortcuts with spotlight, global the from benefited have researchers COVID-19 FRANCESCO BOCCELLATO FRANCESCO CHETAN BETTEGOWDA Ludwig Johns Hopkins Ludwig Oxford Ludwig

27 therapy their careers. their therapy biomedical and research cancer and to make hoped who people to young inhibitory be must It eliminated. been has what than less be must left is what that extent to the direction and oversight health public as well as translation, its and severely biomedical damaged research has pandemic to the response early and appropriate of lack view. The my in Not research. cancer meaningful, reproducible and translatable for required rigor the with but place, taking currently are that collaborations and connectedness worldwide the maintain will we that Ihope emergency, this After response. pandemic inform to required data of speed to the suited well not are which replication, and rigor requires science Medical reproducible. and rigorous still but labor-intensive less to be redesigned to be need will be practiced. Therefore, experiments to have still might distancing social For instance, pandemic. the after norm research to anew come will we I believe Ludwig Johns Hopkins MICHAL CASPI TAL CASPI MICHAL Ludwig Stanford Ludwig Stanford EMILY HSIUE H. IRV WEISSMAN

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask surprisingly good across various platforms. various across good surprisingly control audio and sharing screen find will Many meeting. in-person an matches nearly presentation and conversation of quality the as teleconferencing of acceptance greater in usher help will meetings to face face Limiting potential If so, collaborators? how? with you interact how rethinking are and you network travel ascientist, As worldwide. hampered and meetings of scientific forced the cancellation has pandemic The Chi Van Dang Jason Bugno Ludwig Lausanne IAN MARTEN Ian Marten Spencer S. Watson

28 friendships. for networking and building long-lasting face-to-face meetings are irreplaceable meetings, research collaborative but nimble more catalyze should pandemic the during virtually to meet ability The Ludwig Scientific Director Scientific Ludwig Chetan Bettegowda

CHI VAN CHI DANG

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask person interactionperson is key. in- where sessions on more focused shorter, become meetings Ihope online, entirely meetings academic annual major first the showcasing ASCO and AACR With collaborations. maintain and to network meetings virtual on to rely many prompted consequences of air travel have already carbon the and change Climate interact with other participants. to virtually aplatform provided also year this held meeting AACR on-line The Slack. Twitter and as such avenues digital using by that to substitute trying I’m and basis, adaily on members lab with science discuss to casually able being I miss future. the in fruitful more collaborations distant make will ability this Ihope faces. seeing and slides sharing software, meeting virtual to using accustomed grown all now. We’ve laughable seems That phone. cell their calling and slides of a PDF remote by sending them collaborators with meetings Iconducted past, the In No. KABRAJI SHEHERYAR K. Ludwig Johns Hopkins GERBURG WULF GERBURG Ludwig Harvard Ludwig Harvard ADAM WOLPAW EMILY HSIUE H. Ludwig Wistar

29 after the pandemic has passed. to return need will meetings In-person events. virtual by substituted fully be can conferences scientific that think not I do but site, on not are who collaborators my from to hear calls video used always I have colleagues. with to network conferences video communications and multi-institutional electronic on more relying are we result, As a meetings. scientific of re-formatting or cancellation the forced pandemic The process. lab lockdown-restart entire the during experienced we’ve what share and contacts new of anetwork build to way agreat been it’s and otherwise, seen have wouldn’t Iprobably that research much so about out find I now was. really platform this useful how about years for skeptical pretty been having account, my Twitter activated I finally FRANCESCO BOCCELLATO FRANCESCO Ludwig Johns Hopkins Ludwig Lausanne JOHANNA JOYCE JOHANNA PAUL SURMAN Ludwig Oxford Ludwig

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask academic travel. academic of footprint carbon immense the reducing while collaboration global of level this to maintain trying in forward moving this harness to seriously need We will level. new awhole at institution my of outside researchers with connect to closely and home, my from world the around meetings group and seminars attend to virtually able to be incredible it Yes. found Ihave toconverted online discussions. readily be can they if gatherings/meetings scientific future for travel to minimize plan I technologies, these of robustness the Given pandemic. the during ideas medical and scientific of communication rapid the enable that platforms multiple are there replaced, be never will interactions in-person of aspects human the While pandemic continues. pandemic the of aspect this Ihope acommunity. into individuals scattered globally made has potential. communication The constant their out brought really has necessity but COVID-19, before Zoom and Slack We had apart. further us kept pandemic the as closer grown has collaborators online of network my how amazed I’m CHETAN BETTEGOWDA Ludwig Johns Hopkins SPENCER S. WATSON MICHAL CASPI TAL CASPI MICHAL Ludwig Lausanne Ludwig Stanford

30 convention centers, etc. conferences replace planned meetings at virtual if hurt be will conferences on count that businesses the of all said, That it. from come will alliances new expect and perspectives cell and immunology stem from research COVID-19 to consider meetings hoc ad many to organize ability and time the had Ihave to participate. fellows and students more many allows and this to do to investigators money and time in savings enormous an is It results. better to allow more improve can hopefully teleconference and meetings working, are to methods virtual current that clear is It Ludwig Stanford IRV WEISSMAN

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask controlled. been have could pandemic the when issues political than rather scientific to response early and adequate of lack to overwhelming seat aback take to had all trials clinical and health, through science, medicine, public epidemic to the response our Sadly, this in the from future? happening to done be might prevent What of care. standard normal not patients receiving are this time, cancer many During Irv WeissmanIrv Gerburg Wulf Ludwig Stanford IRV WEISSMAN

Paul Surman Paul Miller without compromising patient outcomes. cancer, hospital thus visits reducing unnecessary of surveillance and therapy diagnosis, remote and technological developments could also facilitate Future plans. biological management and diagnosis of communication particularly telemedicine, of use the increased have events Recent hospital. in delivered is care cancer of majority the Traditionally, 31 Ashvina Segaran ASHVINA SEGARAN ASHVINA

Ludwig Oxford Ludwig

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask the need arises in the future. the in arises need the clinical medicine to be better prepared if for allow will it consults, medical virtual with rises familiarity and infrastructure the As telemedicine. of power the to examine us allowed has pandemic This testing. of level higher amuch require will This care. receive to in coming patients other infect could who cases COVID-19 potential to isolate ways safe to devise have we care, receive to safely to continue patients risk high for to allow order in and infections acquired hospital- of risk aterrible is There future. the in recruitment trial clinical accelerate and care patient cancer tele-visit technologies may even improve of adoption awider barrier, consultation patient-physician the reducing By events. pandemic future during remotely practices care of standard continue to us allow ultimately will This needs. consultation patient all to accommodate place in systems have now and experience invaluable gained also we But hurdles. logistical significant encountered visits tele- of adoption the transitions, rapid any with As consultations. opinion second requiring or care follow-up fortele-visits patients most requiring to transitioned has center cancer Our CHETAN BETTEGOWDA Ludwig Johns Hopkins Ludwig Johns Hopkins MICHAL CASPI TAL CASPI MICHAL Ludwig Stanford PAUL SURMAN

32 review. andevidence-based which could use truly are practices care’ of ‘standard which to examine opportunity this to use is important Equally disruptions. future of face the in care cancer standard of delivery to maintain potential the have medications—all intravenous) than (rather technologies, more or oral injectable wearable telemedicine, of use The circumstances iscircumstances unacceptable. these under even standard the of breach a but modifications, see Ican care. of standard the than other something received have should patient No possible. be should this crises, similar or infections viral unexpected handle can that alevel at kept are capabilities care medical our If occurs. threat emergent an when patients cancer for thatsafeguards maintain essential care place into to put important be will It scenarios. worst-case the mitigates tracing and testing deployable quickly in investment More care. of loss prevent would system medical the overloading avoiding event, related For apandemic KABRAJI SHEHERYAR K. RALPH WEICHSELBAUM RALPH GEOFFREY GREENE GEOFFREY Ludwig Lausanne Ludwig Chicago Ludwig Chicago Ludwig Ludwig Harvard IAN MARTEN

LUDWIG LINK | AUGUST 2020 Ask a scientist a Ask future pandemics. future during patients of good the for guidelines provide collectively and slow-down pandemic the during practices best share to willing are that clinics oncology major from to come have will learned Lessons disadvantage for patients. a instances, many in is, This currently. trials to clinical patients accrue cannot We care. hospice inpatient towards move to decision the accelerates disease COVID the where disease of diagnosis additional metastatic advanced with patients in instances We have do care. of standard encountered any patients not receiving not Ihave true. is this think I don’t years. few next the in patients to protect needed be will approaches new engineering building with along testing to rapid improvements that say Iwould but oncologist, an not I’m unforeseeable events. during even care proper to ensure this experience to be better prepared from learn we that hope Iwould do. won’t care of standard the receiving Not Ludwig Scientific Director Scientific Ludwig GERBURG WULF GERBURG Ludwig Chicago Ludwig Chicago Ludwig Ludwig Harvard SEAN FANNING SEAN JASON BUGNO CHI VAN CHI DANG

33 pharmacies. local by or home at administered to be patients to the therapies the mailing by done be can treatment actual the of Some would make more healthcare accessible. run, long the in which infrastructures, to build up telemedicineopportunity agood is time extraordinary This com/ https://ukcoronaviruscancermonitoring. project: monitoring COVID-19 and cancer UK the See pandemics. and to epidemics treatment cancer modifying in response of extent the on decisions future guide will cases COVID-19 confirmed by stratified outcomes long-term and term discretion. Accumulating data on short- clinician and protocols national by resulted in treatment variations, guided has COVID-19 during cancer Managing events. future any during care to standard close provide to to continue us allow will interventions similar of implementation early Hopefully, care. patient maximizing while staff and providers between interactions to minimize how about pandemic this from deal agreat learned we’ve Clinically, Ludwig Johns Hopkins ADAM WOLPAW EMILY HSIUE H. Ludwig Oxford Ludwig Ludwig Wistar PAUL MILLER

LUDWIG LINK | AUGUST 2020 Required reading Santagata S. PK, Sorger L, Whitesell KA, GN, Li CG, SL, Sarosiek Lindquist Joshi C, Yapp R, Rashid G, Gaglia decisions. fate cell and adaptation stress mediates transition phase HSF1 3(Epub) February 2020 Biology Cell Nature S. Santagata GD, Demetri E, Sicinska M, Bertagnolli PK, Sorger JP, Jagannathan A, Enriquez Marino- K, Malik Z, Du S, Mei JR, Hemming ML, Nathenson MJ, Lin NTRK1. harboring oncogenic fusion of undifferentiated sarcoma metastatic in selitrectinib and larotrectinib to resistance of mechanisms and Response (Epub) 14 February 2020 Oncology Precision JCO Cichowski K. SJ, Elledge PA, Jänne S, Santagata H, Tiv M, Xu ES, Chambers AJ, Redig S, Guillemette CJ, Guild RO, T, Adeyemi Raedt De R, O,Kuzmickas Maertens SL, Guerra lung cancers. KRAS-mutant in vulnerability epigenetic an confers axis gene HOX A deregulated 2[Epub] April 2020 Cell Cancer Ludwig Harvard Fu YX. RR, Weichselbaum EB, W, Chang Lin L, Xue K, Ni KG, Harris W, K, Y, Yang Shi Zheng signaling. STING via immunotherapy based CD47- facilitates microbiota gut Intratumoral accumulation of 6 March 2020 Medicine Journal of Experimental Chicago Ludwig KW, Vogelstein B, Papadopoulos N. N. Papadopoulos B, Vogelstein KW, Kinzler RH, Hruban EK, Fishman C, Tomasetti A, Klein C, Lengauer A, Parker C, P, Walter Bhattacharya R, J, Leeming Vadakara ZM, Salvati JI, Woods L, Kann CD, Still B, Urban DL, Diehl C, Bettegowda S, Zhou N, Malani DD, Rolston LN, Hagmann AA, Patel C, Douville JD, Cohen K, Lahouel HJ, Hwang CS, Adonizio D, Rosica K, Sheridan F, Sanfilippo DH, AT, Ledbetter Warren A, Honushefsky A, Cohain I, Kinde AH, Buchanan AM, Lennon intervention. guide and cancer for screen to PET-CT with combined testing blood of Feasibility print) of ahead (Online 28 April 2020 Science C. Bettegowda S, Zhou S, JT, Athey Vogelstein B, Vogelstein KW, Kinzler N, Papadopoulos B, Mensh R, Xiong A, Koenecke AM, Khalafallah S, Huq NM, Fischer DL, RY, Thomas Bai V, Staedtke MA, MF,Konig Powell antagonists. α using COVID-19 in syndrome storm cytokine Preventing [Epub] 30 April 2020 Investigation Clinical of Journal Ludwig Johns Hopkins T, RK. Jain Stylianopoulos LL, Munn DG, Duda JW, Baish C, F, Voutouri Mpekris immunotherapy. cancer improve normalization strategies to Combining microenvironment 3(Epub) February 2020 USA Sciences of Academy National the of Proceedings -1 adrenergic receptor receptor -1 adrenergic 34 C, Konig MF, Mensh B, Athey S. S. Athey B, MF, Konig C, Mensh Bettegowda S, Zhou B, Vogelstein KW, Kinzler N, Papadopoulos EA, Stuart B, Caffo AM, Khalafallah S, Huq N, Fischer R, Xiong A, Koenecke M, JT, Powell Vogelstein cytokine storm syndrome. from death and syndrome acute respiratory distress preventing for antagonists receptor adrenergic Alpha-1 Preprint 21 April 52020 Version ArVix C, Zippelius A, Ho PC. PC. Ho A, Zippelius C, T, Jandus Merghoub JD, Wolchok SM, Fendt I, Goldberg R, Silverstein E, F, Meylan Picard I, Schulze CH, J, Tsai Fernández-García SR, Mohmood R, MP,Trefny Zappasodi F, X, Xie Tsui Franco YC, H, Wang tumors. in function and survival T cell regulatory supports adaptation CD36-mediated metabolic (Epub) 17 February Nature Immunology 2020 JA. Joyce ME, RT, Hegi Daniel PH, V, Tabar C, Gutin Brennan CA, Brouland JP, Iacobuzio-Donahue S, Nassiri K, Soukup M, Kornete RL, Bowman F, RR, Maas Klemm cells. immune of alterations specific disease- reveals tumors brain in microenvironmental landscape the of Interrogation (Epub) 28 May 2020 Cell Ludwig Lausanne Giordano-Attianese G, Gainza P, Gainza G, Giordano-Attianese therapy. T-cell for switch safety provides a small-molecule receptor antigen chimeric designed A computationally 3[Epub] February 2020 Biotechnology Nature Tammela T, Jacks T, Bhatia SN. T, T, Bhatia Tammela Jacks HE, Fleming C, Martin-Alonso JC, Voog PMK, AP, Westcott Soleimany AD, Warren JD, Kirkpatrick pulmonary protease profiling. noninvasive via mice in cancer lung of detection Urinary 1 April 2020 Medicine Translational Science Ludwig MIT BE. Correia G, Coukos M, Irving BH, Oh P, J, Bonet Reichenbach AJ, Osorio Corria S, Vollers MJ, Kwak S, Kim S, Shui E, Cribioli E, Gray-Gaillard Merghoub T, Balachandran VP. T, Balachandran Merghoub RP, DeMatteo JD, Wolchok SD, Leach M, Gönen Y, DA, Tuveson Park E, U, Elyada Bhanot G, Askan D, Redmond M, Gururajan B, Gasmi A, Ramnarain Z, J, Sethna J, Zhao Ruan LA, J, Rojas Leung JA, Moral cancer immunity. tissue-specific activating by blockade PD-1 amplify ILC2s [Epub] 19 February 2020 Nature Rudensky AY. J, Hambor K, Kadaveru JR, Cross RJ, Ramos S, Violante C-J, Guo W-B, Jin C, J, Mai Verter M, Schizas OI, Isaeva D, Konstantinovsky PT, McKenney C, Campbell Tcells regulatory peripheral acids promotes generation of Bacterial metabolism of bile (Epub) 15 April 2020 Nature MSK Ludwig

LUDWIG LINK | AUGUST 2020 Required reading Ratcliffe PJ. Ratcliffe T, F, Bishop Rastinejad LM, Hodson EJ, Bruick RK, Collinson PA, Robbins KJ, CW, Buckler Pugh I, Argles L, Eckardt JD, Lima AL, Burrell M, JW, Zhang Fielding M, Cheng X, Prange-Barczynska ventilatory control. Mischel PS, Yeo GW, Furnari FB. Yeo GW, Furnari PS, Mischel CC, V, Chen Bafna KA, J, Frazer Ravits AD, Boyer S, J, Miki Ma S, Saberi ND, Nguyen M, D’Antonio FM, Hessenauer RF, KM, Turner S, AD,Markmiller Parisian Hevner JA, Benitez IA, T,Koga Chaim pluripotent stem cells. genetically engineered from derived avatars cancer using development tumor Longitudinal assessment of January 28 2020 Communications Nature Diego San Ludwig 2 HIF- pharmacological of effects rapid and Marked 30 2020 January Investigation Clinical of Journal CX. Song JA, McKeating JM, V, Harris D’Arienzo A, Magri M, Weldon C, Roberts H, Lopopolo P, J, Siejka-Zielińska Y,Liu Cheng TAPS with hydroxymethylation sequencing and methylation DNA read Accurate targeted long- 3 March 2020 Biology Genome Oxford Ludwig α antagonism on hypoxic hypoxic on antagonism SS. Gambhir SX, Wang R, Spitler JK, Lee AM, Y, Bhatt Yu WJ, JH, Kim Choi H, J, Park Kim FB, Achterberg S, Bodapati Yao C, AX, Lozano EH, Choi S, Suh TJ, JH, Ge Kim A, Aalipour A, Esteva D, Escobedo BJ, Lee DD, Won SM, Park excreta. of analysis the via personalized health monitoring for system toilet A mountable 6[Epub] April 2020 Nature Biomedical Engineering CL. Mackall M, Monje PH, Sorensen S, Cheshier SS, Mitra S, Zaidi S, Puget F, Bourdeaut D, O,Surdez Delattre MC, Frühwald M, Hasselblatt S, Pfister M, Kool PD, Johann D, Williamson MA, DW, Finetti Yecies S, P, Xu RG, Mueller Majzner A, Leruste S, Dhingra L, Labanieh S, Heitzeneder A, Delaidelli CM, Graef CW, Mount E, J, Sotillo Theruvath rhabdoid tumors. treatment of atypical teratoid/ for Tcells CAR B7-H3-targeted Locoregionally administered (Epub) 27 April 2020 Medicine Nature Stanford Ludwig 35 Newman AM. Newman MF, Clarke FM, Dirbas Yu D, FB, Qian NA, Lobo FA, Scheeren M, Zabala S, Cai RW, F, Hsieh AH, Kuo Ilagan MJ, Berger A, Bharadwaj A, Manjunath DJ, Wesche SS, Sikandar GS, Gulati developmental potential. of ahallmark is diversity transcriptionalSingle-cell 24 2020Science January M. Diehn AA, LV, Alizadeh Sequist DA, Haber VS, Nair JB, MF, Shrager Berry NS, Lui AN, Leung CA, Jr, BW Kunder Loo HA, JW, Wakelee Neal RB, West KC, Jensen GJ, Berry SS, Gambhir R, Tibshirani R, Burr CL, Costantino SH, Lin HZ, J, Ren Jen AS, PP, Mansfield Massion DJ, Merriott EL, RF, Chen RB, Ko Yoo CH, Bonilla L, Keh Ting Co MC, YJ, Nesselbush Jeon D, Almanza TD, Azad MC, Jin AB, Hui CL, Liu AA, Chaudhuri B, BY, Chen J, Nabet Schroers-Martin H, Stehr EJ, Moding MS, Esfahani DM, Kurtz EG, Hamilton JJ, Chabon detection. cancer lung early non-invasive for features genomic Integrating (Epub) 25 March 2020 Nature

LUDWIG LINK | AUGUST 2020 LUDWIGCANCERRESEARCH.ORG