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Diether Lambrechts CV 1 C URRICULUM VITAE PERSONAL INFORMATION: Name: Diether Lambrechts Date and place of birth: 02-08-1976; Hasselt, Belgium Nationality: Belgium E-mail: [email protected]. be Website: http://www.vibcancer.be ORCID iD: https://orcid.org/0000-0002-3429- 302X Web of Science ResearcherID: AAJ-3167-2020 EDUCATION / TRAINING (CHRONOLOGICAL ASCENDING): 1988 – 1994 1994 – 1996 1996 – 1999 Secondary School at ‘Sint-Jan Berchmans College’, Genk, Belgium BSc in Bio-engineering (Candidate Bio-engineer), KU Leuven, Belgium. MSc in Bio-engineering (Bio-engineer Cell & Gene Biotechnology), KU Leuven, Belgium. Jan 2008–Oct 2008 Visiting Scientist, Wellcome Trust Center for Human Genetics (WTCHG), University of Oxford, UK. RESEARCH EXPERIENCE & POSITIONS (CHRONOLOGICAL ASCENDING): 01/2000 – 05/2003 PhD in Medical Sciences (Promoter: Prof P Carmeliet), KU Leuven, Belgium. 10/2003 – 09/2009 Postdoctoral Researcher, KU Leuven, Belgium. Two FWO fellowships obtained (Promoter: Prof P Carmeliet). 04/2008 – now Group Leader at the VIB Vesalius Research Center, Leuven, Belgium. 10/2009 – 09/2012 Docent (assistant professor), Dept. of Oncology, KU Leuven, Belgium. 10/2012 – 09/2015 Hoofddocent (associate professor), Dept. of Oncology, KU Leuven, Belgium. 08/2015 – now Science Director at the VIB Center for Cancer Biology, Leuven, Belgium. 10/2015 – 09/2019 Hoogleraar (professor), Dept. of Human Genetics, KU Leuven, Belgium. 10/2019 – now Gewoon hoogleraar (full professor), Dept. of Human Genetics, KU Leuven, Belgium. AWARDS AND HONORS: Prize Karel-Lodewijk Verleysen for Human Medicine 2003. Galenus Prize for pharmacology and fundamental research 2004 (jointly with E Storkebaum).

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Page 1: Diether Lambrechts CV D - CV...Diether Lambrechts CV 2 • Prize “Rimaux-Bartier” to support research for treating incurable diseases, FWO, Belgium. • AstraZeneca Award for Translational

Diether Lambrechts CV

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C U R R I C U L U M V I T A E PERSONAL INFORMATION: Name: Diether Lambrechts Date and place of birth: 02-08-1976; Hasselt, Belgium Nationality: Belgium E-mail: [email protected].

be Website: http://www.vibcancer.be ORCID iD: https://orcid.org/0000-0002-3429-

302X Web of Science ResearcherID: AAJ-3167-2020

EDUCATION / TRAINING (CHRONOLOGICAL ASCENDING): 1988 – 1994 1994 – 1996 1996 – 1999

Secondary School at ‘Sint-Jan Berchmans College’, Genk, Belgium BSc in Bio-engineering (Candidate Bio-engineer), KU Leuven, Belgium. MSc in Bio-engineering (Bio-engineer Cell & Gene Biotechnology), KU Leuven, Belgium.

Jan 2008–Oct 2008 Visiting Scientist, Wellcome Trust Center for Human Genetics (WTCHG), University of Oxford, UK.

RESEARCH EXPERIENCE & POSITIONS (CHRONOLOGICAL ASCENDING): 01/2000 – 05/2003 PhD in Medical Sciences (Promoter: Prof P Carmeliet), KU Leuven,

Belgium. 10/2003 – 09/2009 Postdoctoral Researcher, KU Leuven, Belgium. Two FWO

fellowships obtained (Promoter: Prof P Carmeliet). 04/2008 – now Group Leader at the VIB Vesalius Research Center, Leuven,

Belgium. 10/2009 – 09/2012 Docent (assistant professor), Dept. of Oncology, KU Leuven,

Belgium. 10/2012 – 09/2015 Hoofddocent (associate professor), Dept. of Oncology, KU

Leuven, Belgium. 08/2015 – now Science Director at the VIB Center for Cancer Biology, Leuven,

Belgium. 10/2015 – 09/2019 Hoogleraar (professor), Dept. of Human Genetics, KU Leuven,

Belgium. 10/2019 – now Gewoon hoogleraar (full professor), Dept. of Human Genetics, KU

Leuven, Belgium.

AWARDS AND HONORS: • Prize Karel-Lodewijk Verleysen for Human Medicine 2003. • Galenus Prize for pharmacology and fundamental research 2004 (jointly with E

Storkebaum).

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• Prize “Rimaux-Bartier” to support research for treating incurable diseases, FWO, Belgium.

• AstraZeneca Award for Translational Research 2012. • ERC Consolidator Grant awarded in 2014 for the project entitled ‘Cellular Hypoxia

Alters DNA Methylation through Loss of Epigenome OxidatioN’ (CHAMELEON). • Belgian Cancer Research Award 2017 awarded by the Stichting Tegen Kanker for the

project entitled ‘A Nanopore Long-read Sequencing-based Approach to more Accurately Detect Predictive Biomarkers for Cancer Immunotherapy’.

• Agilent Thought Leadership Award 2018 (321k USD) to support a project entitled ‘Discovering Biomarkers of Response to Cancer Immunotherapy: One Cell at a Time’.

• Awarded by Clarivariate as a most-highly cited scientist 2018. This is quite exceptional as only 67 other (mostly senior) Belgian scientists were similarly ranked.

• ERC Proof Of Concept Grant awarded in 2020 for the project entitled ‘Circulating tumor DNA as an epigenetic biomarker for tumor behavior’ (INITIATOR).

MEMBERSHIPS AND AFFILIATIONS: • Board of Directors of the Genomics Core Facility (UZ Leuven and KU Leuven, Belgium). • Board member of the 'Belgian Association for Cancer Research’ (BACR). • Founding member of the Single Cell Omics Institute (SCOI) from KU Leuven • Board member of the steering committee of the Single Cell Core Facility from the VIB-

KU Leuven Center for Cancer Biology • Board member of the VIB Managing Committee. • Active contributor to international genetic consortia (BCAC, OCAC, E2C2). • Science Director of the Sino-Belgian Collaboration Laboratory for Single Cell Analysis

Technologies (with Fudan University, China) • BELAC Auditor NGS - Bioinformatics

PATENT APPLICATIONS: • Responsiveness to Angiogenesis Inhibitors (EP 09167184.2, PCT/EP2010/004761, EP

09167184.2 and US 13/388,840). Licensed by VIB to Hoffmann-La Roche Ltd (2008). • Responsiveness to Angiogenesis Inhibitors (EP 11179498.8), co-inventor. Licensed by

VIB to Hoffmann-La Roche Ltd (2011). • Method for predicting risk of hypertension associated with anti-angiogenesis therapy

(EP 11179500.1), co-inventor. Licensed by VIB to Hoffmann-La Roche Ltd (2011). • Responsiveness to Angiogenesis Inhibitors (EP 11190229.2). Licensed by VIB to

Hoffmann-La Roche Ltd (2011). • Microsatellite instability markers in detection of cancer (US 61/622,383). This patent

was exclusively licensed to Biocartis NV in 2014. • Methylation profiling of CpGs as a biomarker of tumor hypoxia, co-inventor (WO

2016/142295). • Chromosomal instability as a predictive biomarker of Avastin treatment outcome, co-

inventor (2016).

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• Retrotransposon biomarkers to predict response to cancer immunotherapy (EP 19157160.3), co-inventor (2018).

• Predicting chronic allograft injury through ischemia-induced DNA methylation, co-inventor (WO 2019/122303).

• Predicting chronic allograft injury through age-related DNA methylation (EP19180558.9), co-inventor (2020).

• Predicting age using DNA methylation signatures (GB 1908624.8), co-inventor (2020). • Disease detection in liquid biopsies (EP 19219656.6), co-inventor (2020). • Detection of ovarian cancer in liquid biopsies (EP 19219649.1), co-inventor (2020).

ORGANISATION OF MEETINGS: • Annual Meeting of the ‘Belgian Association for Cancer Research‘ (BACR) Meeting,

January 2011, Leuven, Belgium. • Annual Consortium Meeting 2014 of the Breast Cancer Association Consortium

(BCAC), the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), Leuven, Belgium (±200 attendees from 50 different countries).

• Cell-VIB Symposium: Hallmarks of Cancer, 11-13 December 2016, Ghent, Belgium (co-organized with Cell).

• Annual Meeting of the ‘Belgian Association for Cancer Research‘ (BACR) Meeting, January 28 2017, Leuven, Belgium.

• Revolutionizing Next-Generation Sequencing – RNGS VIB Conference (first edition), 20-21 March 2017, Antwerp, Belgium.

• Applied Bioinformatics in Life Sciences Meeting – VIB Conference (2nd edition), 8-9 March, 2018, Leuven Belgium.

MAIN RESEARCH FIELDS: • Keywords: Cancer, Biomarkers, Cancer Immunotherapy, Anti-angiogenesis, Hypoxia,

High-throughput sequencing, (Epi-)genetics, Omics, Liquid biopsies, Single-cell transcriptomics

• Research Expertise: biomarker research in phase 2/3 clinical trials, hot-spot mutation profiling of oncogenes, copy number aberration profiling by whole-genome sequencing or SNP array, targeted resequencing, whole-genome and exome-sequencing of tumors (mouse and human tissue, fresh-frozen and FFPE), transcriptomics (RNA-Seq), epigenome profiling (mDIP-Seq, hmDIP-Seq, WGBS-Seq), sequencing on liquid biopsies (mutations, chromosomal instability, DNA methylation and nucleosome positioning), bio-informatics (analysis of sequencing data, data integration), functional validation of genetic markers using genomics (siRNA technology, genome editing, etc), tumor models (xenografts and xenopatients), single-cell (sc) sequencing application (scRNA-seq using 10X Genomics, scDNA-seq using MissionBio, CITE-seq, scATAC-seq, etc.), long-read sequencing technology, etc.

LECTURES AND SEMINARS AT INTERNATIONAL INSTITUTES OR MEETINGS: • Before 2010: Keynote on the Annual Meeting of European Federation of Physiologic

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Societies (Munich, Germany); Lecture at the Scuole Normale Superiore (Pisa, Italy); Presentation at the Annual Meeting of the Society for Neuroscience, (Atlanta, USA); Speaker on the 2nd Symposium of Fondation André-Delambre (Québec City, Canada); Speaker on the Joint Meeting of the Belgian Society of Human genetics and Nephrology (Brussels, Belgium); Seminar at the Wallenberg Neuroscience Center (Lund University, Sweden); Seminar in Ecole Superieure de Physique et de Chimie Industrielles (Paris, France); Seminar in the Genomics group, Wellcome Trust Center for Human Genetics, (Oxford, UK); Seminar in the Section for Neuroscience (Sheffield University, UK); Lecture at Annual Belgian Breast Meeting (Leuven, Belgium); Lecture at the Targeted Therapy meeting for Colorectal Cancer in Taormina (Sicily, Italy); Lecture at the IMPAKT Breast Cancer Conference (Brussels, Belgium); Presentation at Clinical Investigator Meetings for AstraZeneca (Manchester, UK), Hoffman-La-Roche (Basel, Switzerland) and Sanofi-Aventis (Firenze, Italy); Poster presentation at the Annual ASCO Meeting 2009 (Orlando, USA); Late-breaking Abstract Presentation at the ESMO/ECCO Annual Meeting (Berlin, Germany).

• 2011-2017: Seminar at the Institute for Cancer Research and Treatment (University of Turin, Italy); Presentation at Clinical Investigator Meeting for Merck (Frankfurt, Germany); Seminar at the Belgian Breast Meeting-BBM (Brussels, Belgium); Seminar at London Research Institute (London, UK); Lecture at Annual Irish Association for Cancer Research (IACR) meeting (Belfast, Ireland); Seminar at Erasmus Medical Center (Rotterdam, The Netherlands); Lecture at the Illumina Cancer Meeting (Antwerp, Belgium); Keynote for the Annual Symposium of LCRP (Hasselt University, Belgium); Lecture at the EORTC Postgraduate Course Medical Oncology (Brussels, Belgium; Keynote at ACHOG Course on Angiogenesis (Istanbul, Turkey); Talk at the Illumina User Meeting (Paris, France). Lecture on NGS at pre-IMPAKT training course (Brussels, Belgium); Talk at the TraFo Symposium (Bergisch Gladbach, Germany); Workshop at the Symposium Genetics of Autoimmunity (Leuven, Belgium). Lecture at the 2nd Annual International Conference on Genomics in Europe (Ghent, Belgium); Keynote at “The Epigenetics Revolution: development and disease biology revisited” Symposium (Leuven, Belgium); Lecture at the Angiogenesis Foundation Meeting (Berlin, Germany); Keynote at the Annual kConFab meeting (Cairns, Australia); Talk at the Annual Meeting of the German Genetics Society (Braunschweig, Germany); Symposium on Personalised Treatment in Colorectal Cancer (ESMO Annual Meeting; Amsterdam, The Netherlands); Talk at the Scientific Symposium on “Progress in angiogenesis inhibition in (colorectal) cancer (Mannheim, Germany); Lecture at the International Meeting on Angiogenesis (Amsterdam, The Netherlands); Seminar at Université Libre de Bruxelles (Bruxelles, Belgium); Talk at the BGDO Oncology Course (Maillen, Belgium); Talk at Akershus University Hospital (Oslo, Norway); Lecture at the Clinical Scientist Symposium (Berlin, Germany); Presentation at Roche: State of the art imaging in oncology (Leuven, Belgium); Presentation at AACR Meeting on Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers (Orlando, USA); Annual AACR Meeting 2015, Plenary lecture on “Biomarkers of Antiangiogenic

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Therapy: Are We Lost in Translation" (Philadelphia AACR). 18th International AEK Cancer Congress 2015 (Heidelberg, Germany); Speaker at the EU-Life Scientific Workshop Epigenetics and Disease (BRIC, Copenhagen, Denmark); Speaker at the “From Big-data to Bedside” symposium (Ghent, Belgium); Talk at JLINX symposium by Janssen (Beerse, Belgium); Lecture at the annual IACR Meeting (Cork, Ireland); Speaker at the Cell-VIB Hallmarks of Cancer Meeting, (Ghent, Belgium); Lecture at EULife Meeting (Ghent, Belgium); Speaker at the IMEC ITF2017 Annual Meeting (Antwerp, Belgium); Speaker at the LKI Fundraising event (Leuven, Belgium).

• 2018: Speaker at the Annual Meeting of the Belgian Senology Society (Vilvoorde, Belgium); Invited speaker at Kong Olavs kreftforskningspris 2018 (Oslo, Norway); Invited seminar at the Institute for Genetics and Biophysics (Napels, Italy); Plenary Lecture Annual VIB Symposium (Eindhoven, The Netherlands); Seminar at the INSERM U 1029 (University Bordeaux, France); Visionary seminar on Precision Oncology (DKFZ, Heidelberg, Germany); Speaker at European Digestive Oncology - Research Forum From Phase III trials to registration – and beyond (Leuven, Belgium); Keynote talk ‘Immune profiling in Cancer’ at Research Day Leuvens Kanker Instituut (LKI); Seminar at The National Center for Drug Screening, Chinese Academy of Sciences, Fudan University (Shanghai, China); Keynote at the 7th Scientific Meeting MolecularDiagnostics.be (Antwerp, Belgium); Invited keynote speaker at Belgian Week of Pathology (Brussels, Belgium); Speaker at The Idylla MSI ‘Meet the Investigator’ Event (ESMO, Munich, Germany); Invited speaker at Genomics and Synthetic UK Congress 2018 (London, UK).

• 2019: Keynote speaker at the Worldwide Medical & Medical Effectiveness meeting Bristol-Myers-Squib (Budapest, Hungary); Invited seminar at The Banbury Center think-tank meeting on single-cell analysis (Cold Spring Harbor, New York, USA); Invited keynote speaker at 2019 Queenstown Molecular Biology Meetings in Shanghai, China; Speaker at Learn & Lunch, BMS Benelux (Brussels, Belgium); Invited speaker at Stanford Allumni Technology Outlook Meeting 2019 (Leuven, Belgium); Speaker at the METACAN conference (Leuven, Belgium); Speaker at 3rd Research Day Tumor Immunology and Immunotherapy (Leuven, Belgium); Course at the WGC Advanced Course on RNA Transcriptomics (Wellcome Genome Campus, Cambridge, UK); Speaker at Fourth International IOTA Conference (Leuven, Belgium); Seminar on liquid biopsies at The Institute of Cancer Research (London, UK); Seminar on single-cell profiling at the Centre Hospitalier de Luxembourg (CHL, Luxembourg); Invited talk on single-cell bio-informatics at Boehringer Mannheim (Biberach, Germany); Invited lecture at the Josephine Nefkens Symposium (Rotterdam, The Netherlands); Invited keynote lecture at the 2019 Zhangjiang International Summit on Cell Therapy (Shanghai, China); Presentation at advisory think-tank meeting on single-cell analysis organised by Merck-Serono (MSD) (Boston, USA); Invited speaker at the School of Medicine, Zheijiang University (Hangzhou, China).

• 2020: Keynote speaker “Single-cell transcriptomics” at The Genetics and Genomics of Cancer symposium (Norway, Oslo); Invited talk at the Life-on-Chip conference

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organized by Smart Hub Flemish brabant (Leuven, Belgium); Invited talk on Fulll length scRNAseq at BGI workshop (Leuven, Belgium)

CLINICAL IMPACT OF MY RESEARCH: • MSI testing: In 2013, we were the first to apply whole-genome sequencing to tumors

from patients with a microsatellite unstable tumour and to observe a specific mutation scar in these tumours. This scar was patented and exlusively licensed to the Belgium-based company Biocartis NV (Mechelen, Belgium) in 2014. Based on this patent, Biocartis launched in 2018 a 7-marker assay fully compatible with their Idylla platform to detect microsatellite instability (MSI) in colorectal cancer and other cancers. The assay received CE-IVD clearance in February 2019. It is currently available in almost any country (sublicenced in China by Wondfo and in Japan by Nichirei Biosciences Inc.). Currently, Biocartis has placed 1,129 Idylla instruments (world-wide) and sells 72,000 cartridges on an annual basis. MSI testing is most often used to tailor metastatic CRC of the MSI subtype to checkpoint immunotherapy, and currently Idylla™ MSI is used in 2 registration studies with BMS for FDA registration. In a 44-center comparison study between Idylla™ MSI Assay and routine molecular and immunohistochemistry tests there was an overall concordance of 98.0% between the tests, but Idylla™ MSI Assay had a much lower invalid rate.

• Homologous recombination deficiency (HRD): In 2016, we started a VLAIO project with Multiplicom NV (now Agilent Technologies). As a result of our efforts in this project, a new sequencing kit encompassing 19 genes involved in homologous recombination deficiency (HRD) has been commercialized (launch: early 2020). Additionally, a HRD scarring assay to detect HRD-driven genomic instability has been optimized and will be launched. HRD status is guiding the treatment of ovarian and triple-negative breast cancer with PARP inhibitors.

• Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. De Roock W, Claes B, Bernasconi D, De Schutter J, Biesmans B, Fountzilas G, Kalogeras KT, Kotoula V, Papamichael D, Laurent-Puig P, Penault-Llorca F, Rougier P, Vincenzi B, Santini D, Tonini G, Cappuzzo F, Frattini M, Molinari F, Saletti P, De Dosso S, Martini M, Bardelli A, Siena S, Sartore-Bianchi A, Tabernero J, Macarulla T, Di Fiore F, Gangloff AO, Ciardiello F, Pfeiffer P, Qvortrup C, Hansen TP, Van Cutsem E, Piessevaux H, Lambrechts D, Delorenzi M, Tejpar S. Lancet Oncol. 2010 Aug;11(8):753-62. Web of Science citations=1268. This manuscript was the first to report that BRAF and NRAS mutations negatively predict response to cetuximab (anti-EGFR mAB) in colorectal cancer. After validation in other cohorts, KRAS mutation testing alone has now been extended to more comprehensive RAS (KRAS, BRAF and NRAS) mutation testing in the clinic. Our lab performed all the genotyping experiments for this study. Claes B was a PhD student in my lab.

• Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A,

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Buysschaert I, Coolen J, Mathieu C, Decramer M, Lambrechts D. Thorax. 2010 Mar;65(3):215-20. Web of Science citations=255. Vitamin D deficiency was linked to osteoporosis in COPD, but this manuscript described for the first time a role for vitamin D deficiency in aggrevating COPD, suggesting vitamin D supplementation. A clinical study by Martineau et al. (Lancet Respir Med. 2015) confirmed this hypothesis. Nowadays, many pneumologists indeed prescribe oral vitamin D supplementation for severely-affected COPD patients.

MAJOR RESEARCH FUNDING DURING LAST 5 YEARS: • 2010-2018: KU Leuven (PF/10/016) – Collaborative project SymbioSys: from variome

to phenome (231k€ – co- promoter) • 2013-2016: FWO research project G077213N – Somatic mutation profile and targeted

therapiesfor tumours deficient in their DNA repair system (160k€; promoter). • 2012-2018: HERCULES large-scale infrastructure grant – PACBIO platform: third

generation single-molecule sequencer (1.9M€; co-promoter) • 2014-2019: ERC Consolidator grant – Cellular hypoxia alters DNA methylation through

loss of epigenome oxidation (CHAMELEON) (1.6M€; promoter) • 2015-2018: FWO research project G.0656 – Differences in anti-tumor response

between lung cancer patients with and without COPD (414k€; promoter) • 2015-2018: FWO research project G.0706.15N – Hypoxia mediated changes in DNA

demethylation patterns as a mechanism for anti-angiogenic therapy resistance (264k€; promoter)

• 2015-2019: Kom op tegen Kanker – Combining metabolic and genetic techniques in research on platinum based therapeutic failure in high grade ovarian cancer: from predictable profile to new therapeutic strategies (400k€; co-promoter)

• 2015-2020: EU H2020-PHC-2014-2015 – Breast cancer stratification: understanding the determinants of risk and prognosis of molecular subtypes (B_CAST) (51k€; promoter)

• 2016-2018: KU Leuven Program Funding - Collaborative project SymbioSys: Computational sciences on petabyte scale (2.8M€; co-promoter)

• 2016-2018: VLAIO (Flemish Agency for Innovation and Enterprise)/Multiplicom – Advanced technologies and targeted NGS-based tests to enable early diagnosis, treatment and monitoring of HRR-deficient cancers (465k€; promoter)

• 2017-2018: VLAIO / Biocartis – HBC.2016.0547 – The Idylla MSI Test: From disruptive colorectal cancer test to companion diagnostic for immunotherapy (186k€; promoter)

• 2017-2019: Stichting tegen Kanker (STK, Foundation against Cancer) – A nanopore long-read sequencing-based approach to more accurately detect predictive biomarkers for cancer immunotherapy (345k€; promoter)

• 2011-2017: EU HEALTH-2011.1.1-2 - Collaborative project, Predictive Genomic Biomarkers Methods for Combination Bevacizumab (Avastin) Therapy in Metastatic Colorectal Cancer (ANGIOPREDICT) (636k€; co-promoter)

• 2017-2020: Kom op tegen Kanker (Fight against Cancer foundation) – Circulating tumor DNA as an epigenetic marker of tumor behavior (446k€; promoter)

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• 2017-2021: EU H2020-MSCA-ITN-2017 – Exploiting GLIOblastoma intractability to address European research TRAINing needs in translational brain tumour research, cancer systems medicine and integrative multi-omics (GLIOTRAIN) (207k€; promoter)

• 2018-2022: EU H2020-SC1-2016-2017 - Advancing a Precision Medicine Paradigm in metastatic Colorectal Cancer: Systems based patient stratification solutions (COLOSSUS) – (481k€; co- promoter)

• 2018-2022: KU Leuven Program Funding - Collaborative project SymbioSys: Computational unravelling of the cellular heterogeneity (1.5M€; co-promoter)

• 2018-2022: FWO Medium-scale infrastructure grant – Single cell omics in high throughput and spatial resolution (919k€; co- promoter)

• 2018-2020: Agilent Thought Leadership Award 2018 for the project entitled ‘Discovering Biomarkers of Response to Cancer Immunotherapy: One Cell at a Time’ (321k$; AWARD WINNER)

• 2019-2021: Stichting tegen Kanker - Dissecting complex tumor microenvironment dynamics during immune checkpoint inhibition using single-cell profiling (450k€; promoter)

• 2018-2022: Kom op tegen Kanker Liga (Fight against Cancer foundation) – ‘Unraveling the resistance mechanisms to PI3K/mTOR inhibition and PD-1 blockade in uterine leiomyosarcoma’ (448k€, co-promoter)

• 2019-2024: INNOVATIVE MEDICINES INITIATIVE (IMI) – COLLABORATIVE PROJECT – ‘INTEGRATED IMMUNOPROFILING OF LARGE ADAPTIVE CANCER PATIENTS COHORTS (IMMUCAN)’ (1437K€; CO-PROMOTOR)

• 2019-2024: EU H2020-SC1-BHC-2018-2020 - Resistance under combinatorial treatment in ER+ and ER- breast cancer (RESCUER) – (165k€, co-promoter)

• 2019-2022: ERACoSysMed - Resistance under combinatorial treatment in ER+ and ER- breast cancer (RESCUER) (200k€, co-promoter)

• 2020-2024: FWO research project G0B6120N – T Cell Expansion and Tumour Neoantigen Evolution during Checkpoint Immunotherapy (390k€; promoter)

• 2020-2021: ERC Proof Of Concept – Circulating tumor DNA as an epigenetic biomarker for tumor behavior (INITIATOR) (150k€, promoter)

INDUSTRY COLLABORATIONS: Hoffman-La-Roche: projects to identify biomarkers of bevacizumab outcome (800K€); Sanofi-Aventis: predictive biomarkers for VEGF-TRAP outcome (120K€); Merck Serono: biomarkers for cilengitide therapy (45K€); Exelixis: project with XL184; Janssen: 2 R&D projects on neuropathic pain (±700K€ each; 2008-2012) and an ongoing collaboration for single-cell analysis; Thrombogenics: bio-informatics, data-mining and omics (55K€); Biocartis NV: validation of Apollo platform (50K€) and a VLAIO project on MSI testing (200K€); PUMA Biotechnoloy: design of a HER2 mutation assay (75K€); Bayer: SNP discovery for response to regorafenib (60K€); Multiplicom: VLAIO project on cfDNA (500K€); EISAI: genomic marker predictive of eribulin response in sarcoma (100K€); Agilent Thought Leadership Award 2018 - ‘Discovering Biomarkers of Response to Cancer Immunotherapy: One Cell at a Time’ (321k$, 2018), a collaboration project to test their

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AIO SureSelect Capture kit (43k€, 2019) and Lighthouse sequencer (2020). Bristol-Myers Squibb: tumor mutational burden by whole exome sequencing (15k€). BGI: research collaboration project ‘Alternative Splicing as a Mediator of the Response to Checkpoint Immunotherapy’ (2020).

COMMUNICATION TO THE LAY-AUDIENCE • PRESS RELEASES:

• Diether Lambrechts receives ERC Proof Of Concept grant. 10/01/2020 - Prof. Diether Lambrechts (VIB-KU Leuven Center for Cancer Biology) has been awarded a Proof of Concept grant by the European Research Council. With this grant, he will be able to explore the use of DNA methylation patterns detectable in tumor DNA that circulates in the blood as predictive marker for resistance against cancer treatments.

• Agilent Presents Thought Leader Award to Professor Diether Lambrechts. 20/02/2019 - Agilent Technologies Inc. (NYSE: A) today announced that Professor Diether Lambrechts from the VIB-KU Leuven Center for Cancer Biology has received an Agilent Thought Leader Award in support of his research in cancer genomics.

• Revolutionary molecular diagnostic cancer test. 24/11/2018 - Biocartis launched a fast, accurate msi assay on its idylla™ platform, offering the Potential to predict effective cancer treatment options.

• Scientists identify chromosomal instability as a novel predictive biomarker for cancer drug Avastin. 10/10/2018 - The study, led by researchers at RCSI and the VIB-KU Leuven Center for Cancer Biology in Belgium, is a further important step in the global effort to move towards a more personalised treatment approach for colorectal cancer patients

• Biocartis launches innovative Idylla™ MSI Assay. 17/07/2018 - Idylla™ MSI Assay further strengthens Biocartis’ test menu and offers opportunities to enter the immuno-oncology testing market

• Scientists create a complete atlas of lung tumor cells. 09/07/2018 - Researchers from VIB, Leuven University and University Hospital Leuven studied thousands of healthy and cancerous lung cells to create the first comprehensive atlas of lung tumor cells.

• Major study of genetics of breast cancer provides clues to mechanisms behind the disease. 23/10/2017 - Seventy-two new genetic variants that contribute to the risk of developing breast cancer have been identified by a major international collaboration involving hundreds of researchers worldwide.

• VIB pushes the boundaries of science to develop new diagnostic tools. 27/07/2017 - With their world-leading strengths in molecular research and biotechnology, various VIB labs are paving the way for novel diagnostic tools that will reduce disease burden and save lives by making disease diagnosis better, faster and more flexible.

• Metastatic breast cancers: Characterising the profile of metastases for improved treatment. 24/04/2017 - Researchers at the Jules Bordet Institute, ULB, VIB and KU Leuven published a study offering a better understanding of the progression of breast cancer. The conclusions could have an impact on care for patients suffering from a metastatic breast cancer.

• Multidisciplinary approach for groundbreaking study on tumor epigenetics. 29/10/2016 - A group of researchers lead by Diether Lambrechts (VIB-KU Leuven) explored the mechanisms that cause increased levels of methylation in tumor genes — information that is vital to the adaptation of therapies to fight different types of tumors.

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• Normalizing tumor oxygen supply could be key factor in the fight against cancer. 17/08/2016 - The lack of oxygen in tumor cells changes the cells’ gene expression, thereby contributing to the growth of cancer. This is the main conclusion of a research project led by professor Diether Lambrechts and Dr. Bernard Thienpont (VIB-KU Leuven).

• Researchers at VIB, ULB, KU Leuven uncover new genetic alterations in development of skin cell carcinoma. 13/07/2015 - “These results will be the foundation of many future studies on the genetic aberrations controlling cancer development” - Diether Lambrechts, VIB-KU Leuven

• ERC-grants grants for three VIB scientists: boost for innovative research. 09/12/2013 - ERC-grants grants for three VIB scientists: boost for innovative research.

• Improved diagnostic test for the detection of cancer. 06/12/2013 - Diether Lambrechts (VIB/KU Leuven) and the biotech company, Biocartis, are working together on a new diagnostic test for certain types of cancer.

• Genetic risk factors breast prostate and ovarian cancer exposed. 27/03/2013 - An international consortium has identified more than 80 regions in our DNA that increase a person’s risk of developing breast, prostate and ovarian cancer.

• Biomarker predicts response to cancer treatment. 21/05/2012 - VIB researcher Diether Lambrechts, associated with KU Leuven, has discovered a biomarker that can predict which patients will benefit from treatment with bevacizumab (Avastin).

• New method to reduce error rate in detecting genomic variants by short-read sequencing. 19/12/2011 - VIB scientists describe in Nature Biotechnology a method that reduces the error rate in detecting genomic variants by short-read sequencing technologies Complete Genomics and Illumina.

• VIB licenses software from Real Time Genomics. 01/10/2010 - VIB has licensed the RTG v2 Software from Real Time Genomics, for variant detection with Complete Genomics data.

• Genetic basis of gynecological cancers. 19/09/2010 - Diether Lambrechts identified – in collaboration with several international teams – susceptibility loci for different gynecological cancers. Their findings resulted in three Nature Genetics papers.

• Charity Lectures: Seminar at the Belgian Breast Meeting BBM (October 2010, Zaventem, Belgium); Talk at the celebration symposium for the 80th birthday of Walter Fiers (April 2011, University of Ghent, Belgium); Keynote Lecture at the Leuvense Internistendagen (June 2011, UZ Leuven, Belgium); Session at "StraatTalent", an Initiative from the Stad Leuven (October 2011, Leuven, Belgium); Keynote at Symposium on Oncology (MariaMiddelares, 2013; Ghent, Belgium) to celebrate the opening of their new building and clinical units; Seminar at the Elcker−Ik Center (November 2013, Antwerp, Belgium); Seminar at Leuvens Kanker Instituut Fundraising Dinner (November 2014, Leuven, Belgium); Invited seminar at the University of Hasselt (September 2014, Kortessem, Belgium) to give a talk on 'how to publish high impact factor papers'; Lecture at a Fundrasing Event in Leuven (Levensloop 2014); Lecture at a Fundraising Event in Ronse (Levensloop, 2015); Talk at the ‘Universiteit Derde Leeftijd Leuven’ (May 2018, Leuven, Belgium); Opening lecture academic year at the University of Hasselt for Biomedical Students (September 2019).

• Appearances on Television and Interviews in Newspapers: 2013: De Morgen: Medicijnen op maat aan opmars bezig; Knack: Elke tumor is anders; De Morgen:

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Kanker sneller op te sporen; De Morgen: DNA verklikt kankers; Knack: Ieder DNA en dus ook ieder kankergezwel is uniek; Goed Gevoel: Medicijnen op maat zijn kanker te slim af; Het Laatste Nieuws: DNA test spoort knobbeltje op voor kanker ontstaat; Gazet van Antwerpen: Krijgt u later kanker?; Het Laatste Nieuws: Belgen forceren doorbraak in kankeronderzoek; VRT De Redactie: Genetische risicofactoren voor bepaalde kankers blootgelegd; NOS: Nieuwe DNA-risico's kanker ontdekt; Radio1: ethische vragen omtrent genetische screening; VRT Het Journaal, VTM Nieuws, Canvas−TerZake. 2014: VRT De Redactie: Nieuwe test om kanker op te sporen in de maak; De Standaard: Nieuwe test om kanker op te sporen in de maak; Artsenkrant: Gepersonaliseerde geneeskunde maakt deel uit van ons DNA; Goed Gevoel: We kunnen kanker steeds beter opsporen en bestrijden. 2015: Knack: stilaan wordt kanker een chronische ziekte. 2016: VTM en VRT nieuws: Meer zuurstof geven aan kankercellen remt hun groei af. 2019: “Kankeronderzoeker Diether Lambrechts: Onze kinderen zullen later aan hun kleinkinderen vertellen wat kanker was”, Het Belang Van Limburg; Radio nieuws: Q-Music, JOE FM, De Ochtend op Radio 1, RTBF bulletin, BNR and VPRO (Nederland), De Morgen, De standaard, De Redactie, La Republica, etc.

Additionally, I am frequently consulted by newspapers (e.g., De Morgen) or magazines (Knack, EOS) to critically comment on cancer-related topics.

PAST PHD STUDENTS (WITH THEIR MAJOR PUBLICATION): Ian Buysschaert (Jun 2010; IWT funding); First authorship in Eur Heart J, 31(9)1132-41, 2010. Current position: cardiologist in UZA, Antwerp, Belgium. An Verheyen (Jun 2011; IWT funding); First authorship in Brain, 135 (Pt 9): 2629-41, 2012. Current position: Senior Medical Writer at Janssen Pharmaceutics, J&J, Beerse, Belgium. Joke Dhondt (Nov 2011; IWT funding); First authorship in the FASEB J, 25(5)1461-73, 2011. Current position: Sr Site Management Coordinator at IQVIA. Bart Claes (Jul 2012; IWT funding); First authorship in Lancet Oncology, 13(7)724-33, 2012. Current position: Project manager R&D at Biocartis, Mechelen, Belgium. Diego Andrés García Dios (Jun 2013); First authorship in Gynecol Oncol. 2013 Feb;128(2):327-34.; Betul Tuba Yesilyurt (Jan 2014); Stefanie Schrauwen (Apr 2015); First authorship in Gynecol Oncol. 2015 Jul;138(1):165-73. Current position: Protocol Manager at Bristol-Myers Squibb. Sandrina Lambrechts (Nov 2015); First authorship in Eur J Cancer. 2016 Jan;53:51-64. Current position: gynaecologist-oncologist at Maastricht UMC+. Matthieu Moisse (Nov 2015; FWO funding); First authorship in Human Molecular Genetics 1;21(11):2412-9; 2012. Current position: post-doc KU Leuven. Els Wauters (Dec 2015; FWO funding) First authorship in Eur. Heart J. 2013 Apr;34(13):993-1001. Current position: Staff member UZ Leuven, pneumo-oncologist and assistant professor KU Leuven. Evelyn Despierre (Dec 2015); First authorship in Target Oncol. 2015 Dec;10(4):583-96. Current position: gynecologist at OLV Hospital Aalst, Belgium. Barbara Brouwers (Jun 2016); First authorship in Breast Cancer Res. 2017 Jul 3;19(1):78. Current position: oncologist AZ Sint-Jan Hospital, Bruges, Belgium. Tine Cuppens (Jun 2017); First authorship in Int J Cancer. 2018 Mar 15;142(6):1230-1243. Current position: Medical Science Liaison Oncology at AstraZenica.

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Michael Olvedy (Jun 2017); First authorship in J Clin Invest. 2017 Jun 1;127(6):2310-2325. Current position: Junior Policy Officer - Blue Book trainee at ERCEA. Line Heylen (Sept 2017); First authorship in Kidney Int. 2019 Nov;96(5):1195-1204. Current position: nephrologist at ZOL Hospital Genk, Belgium. Jeroen Depreeuw (Sept 2017); First authorship in Clin Cancer Res. 2017 Dec 1;23(23):7232-7241. Current position: data scientist at Biocartis. Flora D'Anna (Jan 2018); Shared first authorship in Nature. 2016 Sep 1;537(7618):63-68. Current position: Research Data Manager at ELIXIR. Xiaowen Chen (Feb 2018). Adriaan Vanderstichele (Jan 2019); First authorship in Clin Cancer Res. 2017 May 1;23(9):2223-2231. Current position: Staff member UZ Leuven, Gynaecologist-Oncologist. Dominiek Smeets (Oct 2019); First authorship in Nat Commun. 2018 Oct 5;9(1):4112. Current position: Field Application Scientist at Illumina. Currently, I have 18 additional PhD students that are in the course of pursuing their PhD.

PAST AND CURRENT POST-DOCS (WITH THEIR MAJOR PUBLICATION): Joke Reumers (2009-2012; FWO funding); First authorship in Nature Biotechnology, 30(1)61-8, 2011. Current position: Team Lead Computational Biology at Janssen Pharmaceutics, J&J, Beerse, Belgium. Bernard Thienpont (2012-2017; FWO-funding). First authorship in Nature. 2016 Sep 1;537(7618):63-68. Current position: assistant professor KU Leuven. Hui Zhao (2011-2019; FWO funding); First authorship in Elife. 2014 Aug 1;3:e02725. Current position: Senior Bioinformatics Analyst position in Cancer Research UK. Junbin Qian (since 2017). Former postdoctoral researcher at the KU Leuven research lab of Prof. Mathieu Bollen. Jieyi Xiong (since 2018). Former postdoctoral researcher at Max Delbrück Center for Molecular Medicine, Berlin, Germany.

REVIEWING ACTIVITIES • Reviewer for Scientific Journals: Cell, Nat Biotech, NEJM, Nat Med, Nat Cell Biol,

Nat Comm, Cancer Cell, AJRCCM, JACC, Eur Heart J, Eur Resp J, Clin Canc Res, Eur J Canc, Bioinformatics, Brit J Cancer, JCMM, Int J of Gastr and Hep, Proc Am Thor Soc, Plos One, Respir Res, Respiration, Respirology, J As Pac Soc Resp, Disease Markers, Respirology, Pharmacogenet and Genom, Exp Derm, Future Med, Future Onc, Int J of Gyn Cancer, ALS, Eur J of Neurosc, Eur J Pediatrics, Eur J Med Genet, BMC Cancer; on average 10 papers/year.

• Reviewer of Project Applications: Research Grants Council of Hong Kong, Agence Nationale de la Recherche and German Federal Ministry of Education and Research, Dutch Fund for Research (NWO), Tenovus cancer charity (UK), Barts & London charity (UK), Irish Research Council, multiple national PhD and postdoc grants (IWT, VIB, KU Leuven, etc). I am a regular reviewer of the ERC starter, consolidator and advanced grant applications (±3/year).

• Selected jury member of 8 international PhD defenses and >20 PhD defenses at Belgian universities.

• Member of Evaluation Boards: INSERM/AERES 5-year evaluation of Centre Saint-Antoine (2012) and J Zucman INSERM Unit 674, Paris, France. VUMC cancer center 5-year evaluation board, Amsterdam, The Netherlands.

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• Advisory Boards: I served on advisory boards for Hoffman-La-Roche (bevacizumab), Sanofi-Aventis (aflibercept), Bayer AG (regorafenib), Boehringer Mannheim (nindetanib, single-cell analysis), Elli-Lilly (ramucirumab), Merck/MSD (cilengitide, single-cell analysis), Biocartis (MSI biomarker profiling), Astrazeneca/Merck (Molecular Diagnostic Advisory Panel).