NKI

Wilbert Zwart is a senior group leader at the Netherlands Cancer Institute, division of Oncogenomics, where he started his independent lab in 2011. In 2003, he obtained his BSc and MSc at the University of Utrecht. In 2009, he received his Ph.D. (cum laude) from the University of Leiden, based on his work at the Netherlands Cancer Institute in the groups of Rob Michalides and Jacques Neefjes. Funded by a Dutch Cancer Society KWF fellowship, he performed his postdoctoral training with dr. Jason Carroll at the Cancer Research UK Cambridge Research Institute, where he studied cofactor genomics in breast cancer (2009-2011). He joint Oncode Institute as junior groupleader in 2018, and got promoted in 2022 to Oncode senior groupleader. He is appointed as Professor Functional Genomics in Oncology at the Eindhoven University of Technology, and serves as chair for the NKI Translational Research Board and as theme leader Precision Oncology at the NKI. He leads the Oncode Research theme 5, “Identification of critical drug combinations and biomarkers for personalized cancer treatments.”

• 2022 Best research article of the year, non-clinical, Dutch Endocrine Society

• 2021 Movember-Distinguished Gentleman's Ride-PCF Challenge Award (co-recipient)

• 2021 IDEA Development Award, Department of Defense CDMRP

• 2021 Nominee Prix Galien Research Award 2021

• 2021 Best research article of the year, non-clinical, Dutch Endocrine Society

• 2020 Supervision of “Best PhD thesis of the Year Award”, Dutch Endocrine Society

• 2019 IDEA Development Award, Department of Defense CDMRP

• 2019 ASPIRE Award, The Mark Foundation

• 2018 NWO Netherlands Scientific Organization TOP-laureate, co-application with Reuven Agami

• 2016 NWO Netherlands Scientific Organization VIDI-laureate

• 2016 Best research article of the year, clinical, Dutch Endocrine Society

• 2014 Pezcoller Fellowship

• 2014 Bas Mulder Award, Alpe d’HuZes/ Dutch Cancer Society

• 2011 NWO Netherlands Scientific Organization VENI-laureate

• 2009 Thesis Award-Royal Dutch Microscopy Society

• 2009 Dutch Cancer Society KWF fellowship

• 2009 NWO Netherlands Scientific Organization Rubicon

• 2009 PhD Thesis Cum Laude

• 2008 NKI-AVL Award

• 2006 Symposium Award Dutch Cancer Society

1. Mazrooei P, Kron KJ, Zhu Y, Zhou S, Grillo G, Mehdi T, Ahmed M, Severson TM, Guilhamon P, Armstrong NS, Huang V, Yamaguchi TN, Fraser M, van der Kwast T, Boutros PC, He HH, Bergman AM, Bristow RG, Zwart W*, Lupien M*. Cistrome Partitioning Reveals Convergence of Somatic Mutations and Risk Variants on Master Transcription Regulators in Primary Prostate Tumors. Cancer Cell. 2019 Dec 9;36(6):674-689.e6.

2. Linder S, Hoogstraat M, Stelloo S, Eickhoff N, Schuurman K, de Barros H, Alkemade M, Bekers EM, Severson TM, Sanders J, Huang CF, Morova T, Altintas UB, Hoekman L, Kim Y, Baca SC, Sjöström M, Zaalberg A, Hintzen DC, de Jong J, Kluin RJC, de Rink I, Giambartolomei C, Seo JH, Pasaniuc B, Altelaar M, Medema RH, Feng FY, Zoubeidi A, Freedman ML, Wessels LFA, Butler LM, Lack NA, van der Poel H*, Bergman AM*, Zwart W*. Drug-Induced Epigenomic Plasticity Reprograms Circadian Rhythm Regulation to Drive Prostate Cancer toward Androgen Independence Cancer Discov. 2022 Sep 2;12(9):2074-2097.

3. Pomerantz MM, Qiu X, Zhu Y, Takeda DY, Pan W, Baca SC, Gusev A, Korthauer KD, Severson TM, Ha G, Viswanathan SR, Seo JH, Nguyen HM, Zhang B, Pasaniuc B, Giambartolomei C, Alaiwi SA, Bell CA, O'Connor EP, Chabot MS, Stillman DR, Lis R, Font-Tello A, Li L, Cejas P, Bergman AM, Sanders J, van der Poel HG, Gayther SA, Lawrenson K, Fonseca MAS, Reddy J, Corona RI, Martovetsky G, Egan B, Choueiri T, Ellis L, Garraway IP, Lee GM, Corey E, Long HW, Zwart W*, Freedman ML.* Prostate cancer reactivates developmental epigenomic programs during metastatic progression. Nat Genet. 2020 Aug;52(8):790-799.

4. Prekovic S, Schuurman K, Mayayo-Peralta I, Manjón AG, Buijs M, Yavuz S, Wellenstein MD, Barrera A, Monkhorst K, Huber A, Morris B, Lieftink C, Chalkiadakis T, Alkan F, Silva J, Győrffy B, Hoekman L, van den Broek B, Teunissen H, Debets DO, Severson T, Jonkers J, Reddy T, de Visser KE, Faller W, Beijersbergen R, Altelaar M, de Wit E, Medema R, Zwart W. Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer Nat Commun. 2021 Jul 16;12(1):4360.

5. Severson TM, Kim Y, Joosten SEP, Schuurman K, van der Groep P, Moelans CB, Ter Hoeve ND, Manson QF, Martens JW, van Deurzen CHM, Barbe E, Hedenfalk I, Bult P, Smit VTHBM, Linn SC, van Diest PJ, Wessels L, Zwart W. Characterizing steroid hormone receptor chromatin binding landscapes in male and female breast cancer. Nat Commun. 2018 Feb 2;9(1):482.

Lodewyk Wessels is the head of the Computational Cancer Biology group at the Netherlands Cancer Institute in Amsterdam, The Netherlands. Dr Wessels received his M.Sc. and Ph.D. both from the Department of Electronic and Computer Engineering, University of Pretoria, South Africa. From 1993 to 1997 he was a member of the Center for Spoken Language Understanding at the Oregon Graduate School of Science and Technology, initially as graduate student and later as post-doctoral fellow. In 1997 he joined the Faculty of Electrical Engineering, Mathematics and Computer Science at the Delft University of Technology and was appointed assistant professor in 2002. In 2006 he became a faculty member at the Netherlands Cancer Institute in Amsterdam, The Netherlands. He was appointed chair of Computational Cancer Biology at the Technical University in Delft in April 2012 and heads the Cancer Systems Biology Center at the Netherlands Cancer Institute.

Important contributions to computational cancer biology include the development of novel algorithms for the identification of 1) driver genes in insertional mutagenesis screens (CIMPL, de Ridder et al. 2006); 2) driver genes from copy number profiles (ADMIRE (van Dyk et al, 2013) and RUBIC (van Dykl et al 2016)); interactions between aberrations in tumors (DISCOVER, Canisius et al 2016) and the identification of logic combinations of aberrations that explain drug response (LOBICO, Knijnenburg et al 2016). The Wessels group also collaborated with experimental groups on several landmark papers including 1) the mapping of the genetic landscape of mouse models of lymphomagenesis (Uren et al 2008); mapping chromatin position effects (Akhtar et al 2013) and charting the landscape of pahamacogenomic interactions in cancer (Iorio et al 2016).

• 2010: Cancer Systems Biology Center, NWO

1. Akhtar, W., de Jong, J., Pindyurin, A. V., Pagie, L., Meuleman, W., de Ridder, J., ... & van Steensel, B. (2013). Chromatin position effects assayed by thousands of reporters integrated in parallel. Cell, 154(4), 914-927.

2. de Jong, J., Akhtar, W., Badhai, J., Rust, A. G., Rad, R., Hilkens, J., ... & de Ridder, J. (2014). Chromatin landscapes of retroviral and transposon integration profiles. PLoS genetics, 10(4), e1004250.

3. Farazi, T. A., ten Hoeve, J. J., Brown, M., Mihailovic, A., Horlings, H. M., van de Vijver, M. J., ... & Wessels, L. F. (2014). Identification of distinct miRNA target regulation between breast cancer molecular subtypes using AGO2-PAR-CLIP and patient datasets. Genome biology, 15(1), R9.

4. Iorio, F., Knijnenburg, T. A., Vis, D. J., Bignell, G. R., Menden, M. P., Schubert, M., ... & Cokelaer, T. (2016). A landscape of pharmacogenomic interactions in cancer. Cell, 166(3), 740-754.

5. Van Dyk, E., Hoogstraat, M., Ten Hoeve, J., Reinders, M. J., & Wessels, L. F. (2016). RUBIC identifies driver genes by detecting recurrent DNA copy number breaks. Nature communications, 7, 12159.

Emile Voest is medical director of the Netherlands Cancer Institute, senior scientist of the Oncode Institute, medical oncologist and translational scientist. In addition to his clinical and managerial responsibilities he is leading his own research group. His laboratory group is devoted to bringing personalized medicine to patients and is focused on mechanistic studies and identification of biomarkers that predict treatment efficacy. The results from these studies are subsequently translated in clinical studies. These translational approaches are performed across tumor types with emphasis on epithelial tumors.

His research is in the area of personalized medicine consists of large scale genomic sequencing of patients with metastatic cancer, the development of primary cultures of tumors for ex vivo testing (including tumor organoids) and the use of these cultures to improve drug development and to determine which treatment is best for a specific patient.

1. Natasja L. de Vries^1,2*, Joris van de Haar^3,4,5*, Vivien Veninga^3,4*, Myriam Chalabi^3,6,7*, Marieke E. Ijsselsteijn¹, Manon van der Ploeg¹, Jitske van den Bulk¹, Dina Ruano¹, Jose G. van den Berg⁸, John B. Haanen^3,7, Laurien J. Zeverijn^3,4, Birgit S. Geurts^3,4, Gijs F. de Wit^3,4, Thomas W. Battaglia^3,4, Hans Gelderblom⁹, Henk M.W. Verheul¹⁰, Ton N. Schumacher^3,4,11, Lodewyk F.A. Wessels^4,5,12, Frits Koning^2#, Noel F.C.C. de Miranda^1#, Emile E. Voest^3,4# Gamma delta T cells are effectors of immune checkpoint blockade in mismatch repair-deficient colon cancers with antigen presentation defects. Nature, 2022 in press

2. Chiara M. Cattaneo^1,2,3, Thomas Battaglia^1,2,‡, Jos Urbanus^1,2,‡, Ziva Moravec¹, Rhianne Voogd¹, Rosa de Groot⁴, Koen Hartemink⁵, John B.A.G. Haanen^1,6, Emile E. Voest^1,2,6,#, Ton N. Schumacher^1,2,#,*, and Wouter Scheper^1,#,* Identification of patient-specific T cell neoantigens through HLA-unbiased genetic screens. Nature Biotechnology, 2022, in press

3. L.J. Zeverijn*^1,2, S. Barjesteh van Waalwijk van Doorn-Khosrovani*³, A. Pisters-van Roy³, L. Timmers⁴, T.H.L. Tran⁴, J.E. de Boer⁴, G.F. de Wit^1,2, B.S. Geurts^1,2, H. Gelderblom⁵, H.M.W. Verheul⁶, N. Blijlevens⁷, A.N.M. Wymenga⁸, F.A.L.M. Eskens⁹, E.F. Smit^10,11, H.J. Bloemendal⁶, E.E. Voest^1,2Harmonising patient-access programmes: the Dutch DRUG Access Platform. Lancet Oncology2022, Feb;23(2):198-201.

4. L.R. Hoes^1,2, J.M. van Berge Henegouwen^2,3, H. van der Wijngaart^2,4, L.J. Zeverijn^1,2, D.L. van der Velden¹, J. van de Haar^1,2,5, P. Roepman⁶, W.W.J. de Leng⁷, A.M.L. Jansen⁷, E. van Werkhoven⁸, V. van der Noort⁸, A.D.R. Huitema^9,10’11 , E.H. Gort¹², J.W.B. de Groot¹³, E.D. Kerver¹⁴, D.J. de Groot¹⁵, F. Erdkamp¹⁶, L.V. Beerepoot¹⁷, M.P. Hendriks¹⁸, E.F. Smit¹⁹, W.T.A. van der Graaf²⁰, C.M.L. van Herpen²¹, M. Labots³, A. Hoeben²², H. Morreau²³, M.P. Lolkema^24,26, E. Cuppen^2,6,25, H. Gelderblom³, H.M.W. Verheul²¹, E.E. Voest^1,2,26 Genomics –Guided Treatment of Patients With Rare Cancers in the Drug Rediscovery Protocol (DRUP). Clin Cancer Res 2022, 28(7):1402-1411

5. Luuk J. Schipper, Laurien J. Zeverijn, Mathew J. Garnett, Emile E. Voest Can drug repurposing accelerate precision oncology? Cancer Discovery, 2022, June 1

6. Joaquin Mateo^1†, Lotte Steuten^2,3†, Philippe Aftimos⁴, Fabrice André⁵, Mark Davies⁶, Elena Garralda¹, Jan Geissler⁷, Don Husereau⁸, Iciar Martinez-Lopez⁹, Nicola Normanno¹⁰, Jorge S. Reis-Filho¹¹, Stephen Stefani¹², David M. Thomas¹³, C. Benedikt Westphalen^14,15 and Emile Voest^16,17* Delivering precision oncology to cancer patients. Nature Medicine, 2022, 28(4):658-665

Dr. Karin E. de Visser obtained her PhD at the Division of Immunology at the Netherlands Cancer Institute in Amsterdam in the field of tumor immunotherapy. From 2003-2005 she worked as a postdoctoral fellow of the Dutch Cancer Society in the lab of Dr. Lisa Coussens in the Cancer Research Institute at the University of California, San Francisco, where she developed an active interest in the interplay between adaptive and innate immune system during cancer development. She discoverd a novel promoting role for B lymphocytes during inflammation-associated skin carcinogenesis.

In 2005 she joined the laboratory of Dr. Jos Jonkers at the Division of Molecular Biology at the Netherlands Cancer Institute, where she expanded her research direction into the field of inflammation and mammary carcinogenesis, using conditional mouse models. Currently she is group leader at the Division of Immunology at the Netherlands Cancer Institute. The overall goal of her research is to understand by which mechanisms the immune system influences breast cancer metastasis and response to conventional anti-cancer therapies. Through mechanistic understanding of the crosstalk between the immune system and cancer cells she aims to contribute to the design of novel immunomodulatory strategies to fight metastatic breast cancer and to increase the efficacy of anti-cancer therapy response.

A recent breakthrough of her lab is the discovery that mammary tumors induce a systemic inflammatory response involving γδT cells and neutrophils to facilitate metastasis formation (Coffelt et al. Nature 2015). Karin de Visser received a prestigious ERC consolidator grant in 2014, she is recipient of the 2015 Metastasis Research Prize of the Beug Foundation and in 2016 she was selected as a member of the EMBO young investigator program. Please have a look at her website for more information.

• 2017: Invited member of The Academy of Europe (Academia Europaea)

• 2016: Selected as an EMBO Young Investigator (EMBO YIP)

• 2015: The Metastasis Research Price for advanced researchers of the Beug Foundation for Metastasis Research

• 2014: ERC consolidator grant laureate

• 2009: NWO-VIDI laureate

• 2009: NWO/Aspasia award: career advancement award of the Innovational Research Incentives Scheme of NWO.

• 2003: AACR-Women in cancer research Brigid G. Leventhal Scholar-in-Training Award for participation in the 94th AACR Annual Meeting, 2003.

• 2003-2005: Dutch Cancer Society (KWF) fellowship for fundamental and (pre)-clinical cancer research

1. Ciampricotti, M., Hau, C. S., Doornebal, C. W., Jonkers, J., & De Visser, K. E. (2012). Chemotherapy response of spontaneous mammary tumors is independent of the adaptive immune system. Nature medicine, 18(3), 344.

2. Coffelt, S. B., Kersten, K., Doornebal, C. W., Weiden, J., Vrijland, K., Hau, C. S., ... & de Visser, K. E. (2015). IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature, 522(7556), 345.

3. Coffelt, S. B., Wellenstein, M. D., & de Visser, K. E. (2016). Neutrophils in cancer: neutral no more. Nature Reviews Cancer, 16(7), 431.

4. Doornebal, C. W., Klarenbeek, S., Braumuller, T. M., Klijn, C. N., Ciampricotti, M., Hau, C. S., ... & de Visser, K. E. (2013). A preclinical mouse model of invasive lobular breast cancer metastasis. Cancer research, 73(1), 353-363.

5. Kersten, K., Coffelt, S. B., Hoogstraat, M., Verstegen, N. J., Vrijland, K., Ciampricotti, M., ... & Doshi, P. (2017). Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages. Oncoimmunology, 6(8), e1334744.

Daniela Thommen obtained her PhD in 2010 at the University of Basel, Switzerland (Prof. Barbara Biedermann) for her studies on the role of antigen-specific cytotoxic T cells in endothelial damage. She then performed her residency training in Internal Medicine at the St. Claraspital Basel and in Medical Oncology at the University Hospital Basel, obtaining her board certification in 2015. In parallel to her clinical specialization, she worked as a postdoctoral fellow in the lab of Prof. Alfred Zippelius at the Department Biomedicine in Basel, focusing on the role of intratumoral T cell heterogeneity in the response to immune checkpoint blockade in human lung cancer. In 2016, she joined the group of Prof. Ton Schumacher at the Netherlands Cancer Institute supported by a postdoc fellowship from the Swiss National Science Foundation, with the goal to develop ex vivo technologies for functionally studying T cell responses in human cancer samples. In 2020, she started her own lab as junior group leader and obtained tenure in 2023, joining the Netherlands Cancer Institute as permanent staff. Her research focusses on understanding the heterogeneity in intratumoral immune cell activity and its impact on treatment response or resistance. To this end, her group develops and exploits human tumor explant models to study patient-specific immunotherapy responses ex vivo and to develop new personalized immunotherapy strategies. 

• 2023    Aspasia Award

• 2022    VIDI research grant (NWO)

• 2021    Arthur and Sandra Irving Cancer Immunology Scholar

• 2020    Melanoma Research Alliance Team Science Award

• 2019    KWF Young Investigator grant, Bas Mulder Award

• 2019    Swiss Pfizer Research Prize in Oncology

• 2019    SITC Women in Cancer Immunotherapy Network (WIN) Leadership Institute

• 2017    LIBRA Career Development Compass (EU-LIFE)

• 2016    Antelope Medical Professorship Program (University of Basel)

• 2016    Advanced Postdoc Mobility fellowship (Swiss National Science Foundation)

1. Kaptein P*, Jacoberger-Foissac C*, Dimitriadis P*, Voabil P, de Bruijn M, Brokamp S, Reijers I, Versluis J, Nallan G, Triscott H, McDonald E, Tay J, Long GV, Blank CU†, Thommen DS†, Teng MWL†. Addition of interleukin-2 overcomes resistance to neoadjuvant CTLA4 and PD1 blockade in ex vivo patient tumors. Sci Transl Med 2022, 14(642):eabj9779. (*shared first authors, †shared senior authors)
    

2. Hummelink K, van der Noort V, Muller M, Schouten RD, Lalezari F, Peters D, Theelen WSME, Koelzer VH, Mertz KD, Zippelius A, van den Heuvel MM, Broeks A, Haanen JBAG, Schumacher TN, Meijer GA, Smit EF, Monkhorst K*, Thommen DS*. PD-1^T TILs as a predictive biomarker for clinical benefit to PD-1 blockade in patients with advanced NSCLC. Clin Cancer Res 2022, 28(22):4893- 4906. (*shared senior authors)
    

3. Schumacher TN and Thommen DS. Tertiary lymphoid structures in cancer. Science 2022, 375(6576): eabf9419.
    

4. Voabil P*, de Bruijn M*, Roelofsen LM*, Hendriks SH, Brokamp S, van den Braber M, Broeks A, Sanders J, Herzig P, Zippelius A, Blank CU, Hartemink KJ, Monkhorst K, Haanen JBAG, Schumacher TN†, Thommen DS†. An ex vivo tumor fragment platform to dissect response to PD-1 blockade in cancer. Nat Med 2021, 27(7):1250-1261. (*shared first authors, †shared senior authors)
    

5. Thommen DS*, Koelzer VH, Herzig P, Roller A, Trefny M, Dimeloe S, Kiialainen A, Hanhart J, Schill C, Hess C, Savic Prince S, Wiese M, Lardinois D, Ho PC, Klein C, Karanikas V, Mertz KD, Schumacher TN, Zippelius A*. A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat Med 2018, 24(7):994-1004. (*Co-corresponding authors)

Bas van Steensel received his PhD in 1995 from the University of Amsterdam, where he studied the role of nuclear organization in steroid receptor function. As a postdoc he studied human telomere-binding proteins in the lab of Titia de Lange (the Rockefeller University) and he developed a technique for mapping of protein-DNA interactions in the lab of Steven Henikoff (FHCRC, Seattle). He set up his own lab at the University of Amsterdam in 2001, and moved to the Netherlands Cancer Institute in 2002. Since 2010 he is also adjunct Professor in Chromosome Biology at Erasmus Medical Centre, Rotterdam.

• 2022: ERC Advanced Grant

• 2016: ERC Advanced Grant

• 2011: ERC Advanced Grant

• 2008: EMBO Membership

• 2004: European Young Investigator (EURYI) Award

• 2001: EMBO Young Investigator Programme

• 2000: Annual Award, Netherlands Society for Biochemistry and Molecular Biology

• 2000: Researcher of the Netherlands Academy of Sciences (KNAW)

• 1995: Human Frontier Science Program Long-Term Fellowship

1. Akhtar, W., de Jong, J., Pindyurin, A. V., Pagie, L., Meuleman, W., de Ridder, J., ... & van Steensel, B. (2013). Chromatin position effects assayed by thousands of reporters integrated in parallel. Cell, 154(4), 914-927.

2. Kind, J., Pagie, L., de Vries, S. S., Nahidiazar, L., Dey, S. S., Bienko, M., ... & Fudenberg, G. (2015). Genome-wide maps of nuclear lamina interactions in single human cells. Cell, 163(1), 134-147.

3. van Arensbergen J, Pagie L, FitzPatrick VD, de Haas M, Baltissen MP, Comoglio F, van der Weide RH, Teunissen H, Võsa U, Franke L, de Wit E, Vermeulen M, Bussemaker HJ, van Steensel B. (2019). High-throughput identification of human SNPs affecting regulatory element activity. Nat Genet. 51:1160-1169.

4. Leemans C, van der Zwalm MCH, Brueckner L, Comoglio F, van Schaik T, Pagie L, van Arensbergen J, van Steensel B. (2019). Promoter-intrinsic and local chromatin features determine gene repression in LADs. Cell 177:852-864.

5. Martinez-Ara M, Comoglio F, van Arensbergen J, van Steensel B. (2022). Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome. Mol Cell. 82:2519-2531

Titia K. Sixma received her Ph.D. training in the group of Wim Hol at Groningen University determining crystal structures of a bacterial protein toxin homolog of cholera toxin, LT and she worked as a post-doctoral fellow in the group of Paul Sigler at Yale University. Currently she is group leader (since 1994) at the Netherlands Cancer Institute in Amsterdam. She uses structural biology/biochemistry and biophysical analysis to study the regulation of cellular signaling processes. The group is particularly interested in the proteins involved in ubiquitin conjugation and DNA mismatch repair. Since 2004 she has a part-time appointment as professor at the ErasmusMC in Rotterdam.

Titia Sixma is interested in the regulation of genome maintenance. Her approach is mechanistic, using high resolution methods in well-defined systems, that allow quantitative analysis and high resolution detail, thus providing insight in specific function and regulation, thus yielding important insights for drug development. She focusses particularly on the role of ubiquitin signalling and DNA mismatch repair

Major breakthroughs include the elucidation of DNA mismatch repair conformational states and the structure solution of AChBP, the first Cys-loop receptor ligand binding domain structure. More recent highlights were the elucidation of a novel chromatin mark on H2A after DNA damage, the definition of allosteric regulatory mechanisms for deubiquitinating enzymes and the characterization of specificity in ubiquitin E3 ligases DNA damage response and LUBAC.

• 2008: Elected member of the KNAW (Royal Netherlands Academy of Arts and Sciences)

• 2008:Elected member of Academiae Europaea

• 2004: Elected member of EMBO

• 1994: NVBMB Prize

1. Fernandez-Leiro R, Bhairosing-Kok D, Kunetsky V, Laffeber C, Winterwerp HHK, Groothuizen F, Fish A Lebbink JHG, Friedhoff P, Sixma TK, Lamers MH. (2021) The selection process of licensing a DNA mismatch for repair. Nat Struct Mol Biol Apr;28(4):373-381.

2. Dharadhar S, van Dijk WJ, Scheffers S, Fish A, Sixma TK (2021) Insert L1 is a central hub for allosteric regulation of USP1 activity, EMBO Rep. 22(4) e51749

3. Kim RQ, Geurink PP, Mulder MPC, Fish A, Ekkebus R, El Oualid F, van Dijk WJ, van Dalen D, Ovaa H, van Ingen H, Sixma TK. (2019) Kinetic analysis of multistep USP7 mechanism shows critical role for target protein in activity. Nat Commun. 10(1):231.

4. Sahtoe DD, van Dijk WJ, Ekkebus R, Ovaa H, Sixma TK. (2016) BAP1/ASXL1 recruitment and activation for H2A deubiquitination. Nat Commun. 7, 10292.

5. Mattiroli F, Vissers JHA, van Dijk WJ, Ikpa P, Citterio E, Vermeulen W, Marteijn JA, Sixma TK. (2012) RNF168 Ubiquitinates K13-15 on H2A/H2AX to Drive DNA Damage Signaling. Cell. 150, 1182-95.

Ton Schumacher started his career in 1988 in the lab of Hidde Ploegh at The Netherlands Cancer Institute, as a PhD student working on antigen presentation by MHC molecules. After his PhD (1992), and a brief stint with Ploegh at MIT, he moved to the lab of Peter Kim at The Whitehead Institute (Cambridge, USA), where he developed novel technologies for drug discovery. In 1996, he became PI at The Netherlands Cancer institute, a position that he combines with a professorship at Leiden University since 2005. In his research, Schumacher aims to understand how the T cell-based immune system can recognize and destroy cancer cells. Key highlights in this work have been:

• Development of a series of technologies to measure which fragments from (tumor) antigens can be presented by MHC molecules.

• Provision of the first in vivo proof of principle for the potential value of T cell receptor gene therapy to induce defined tumor-specific T cell responses.

• Development of the concept of cellular barcoding to reveal single immune cell behavior in vivo, and the subsequent use of this technology to reveal fundamental aspects of immune responses.

• Development of high-throughput technology to measure T cell responses to patient-specific tumor antigens, and the subsequent demonstration that T cell responses against neo-antigens are common in tumors with high levels of DNA damage, and can be enhanced by immunotherapy. The latter data have contributed to the ongoing development of personalized cancer immunotherapies that aim to selectively boost T cell reactivity against patient-specific neo-antigens.

• Demonstration of the superior immune activating capacity of immune checkpoint blockade in cancer patients when given before surgery, providing a rationale for the ongoing broader clinical development of neoadjuvant cancer immunotherapy

In addition to his academic work, Schumacher is venture partner at Third Rock Ventures and co-founder of 6 biotech companies that develop antibody-, T cell-, and vaccine-based cancer immunotherapies.

• 2021: Louis-Jeantet Prize for Medicine

• 2021: Elected Fellow of the AACR Academy

• 2021: Elected member Royal Netherlands Academy of Arts and Sciences

• 2021: AACR-CRI Lloyd J. Old Award

• 2021: Elected member Royal Holland Society of Sciences and Humanities

• 2020: Simon Stevin Award

• 2018: Honorary Member EATI

• 2017: Academia Europaea Member

• 2016: Peter Speiser Award

• 2016: van Loghem Award

• 2016: W.B. Coley Award

• 2015: Meyenburg Cancer Research Award

• 2014: San Salvatore Award

• 2014: Queen Wilhelmina Research Award

• 2014: Fellow European Academy of Cancer Sciences

• 2013: Scientific Advisory Council, The Cancer Research Institute

• 2010: EMBO Member

• 2010: Amsterdam Inventor Award

• 2000: Pioneer Award

• 1994-1996: Howard Hughes Medical Institute Fellow, The Life Sciences Research Foundation

1. Ariotti, S., Hogenbirk, M. A., Dijkgraaf, F. E., Visser, L. L., Hoekstra, M. E., Song, J. Y., ... & Schumacher, T. N. (2014). Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert. Science, 346(6205), 101-105.

2. Gerlach, C., Rohr, J. C., Perié, L., van Rooij, N., van Heijst, J. W., Velds, A., ... & Schumacher T. N. (2013). Heterogeneous differentiation patterns of individual CD8+ T cells. Science, 340(6132), 635-639.

3. Linnemann, C., Van Buuren, M. M., Bies, L., Verdegaal, E. M., Schotte, R., Calis, J. J., ... & Schumacher T. N. (2015). High-throughput epitope discovery reveals frequent recognition of neo-antigens by CD4+ T cells in human melanoma. Nature medicine, 21(1), 81-85.

4. Mezzadra, R., Sun, C., Jae, L. T., Gomez-Eerland, R., de Vries, E., Wu, W., ... & Schumacher T. N. (2017). Identification of CMTM6 and CMTM4 as PD-L1 protein regulators. Nature, 549(7670), 106-110.

5. Strønen, E., Toebes, M., Kelderman, S., van Buuren, M. M., Yang, W., van Rooij, N., ... & Schumacher, T. N. (2016). Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science, 352(6291), 1337-1341.

6. Blank, C. U., Rozeman, E.A., Fanchi, L.F, Sikorska, K., van de Wiel, B., Kvistborg, P., … & Schumacher T. N. (2018). Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Nature medicine, 24(11), 1655-1661..

Jacco van Rheenen was originally trained in a variety of imaging techniques during his PhD with Dr. Kees Jalink at the Netherlands Cancer Institute. He was among the first to optimize imaging and develop software to quantitatively measure FRET on confocal microscopes. In order to broader his scales, he obtained a KWF fellowship to do a postdoc in the United States in the lab of Dr. John Condeelis at the Albert Einstein College of Medicine. There he extended his imaging experience by imaging mammary tumors intravitally including two-photon microscopy and became an expert in the field of intravital FRET imaging.

In 2008 he was appointed as group leader at the Hubrecht Institute, where he utilizes his imaging techniques to visualize processes that are required for the metastasis of tumor cells in living animals. In July 2014 he was appointed professor in Intravital Microscopy at the University Medical Center Utrecht. In October 2017 he became senior group leader at the Netherlands Cancer Institute (NKI) in Amsterdam. In 2009, he was awarded a VIDI award from Netherlands Organization for Scientific Research. In 2013, he received the Stem Cells Young Investigator Award. In 2015, he was awarded an ERC consolidator grant, and in 2017 the Dr. Josef Steiner Cancer Research Foundation Award.

• 2022 VICI award, Netherlands Organisation for Scientific Research (NWO), Netherlands

• 2019 Ammodo Science Award, Netherlands

• 2017: Dr. Josef Steiner Cancer Research Foundation Award

• 2015: ERC consolidator grant by the European Research Counsel

• 2013: Stem Cells Young Investigator Award 2013

• 2008: VIDI grant by the Netherlands Organisation for Scientific Research (NWO)

• 2006: Fellowship for fundamental and (pre-)clinical cancer research from the Dutch Cancer Society (KWF).

1. Azkanaz M, Corominas-Murtra B, Ellenbroek SIJ, Bruens L, Webb AT, Laskaris D, … & van Rheenen J. Retrograde movements determine effective stem cell numbers in the intestine. Nature. 2022 Jul;607(7919):548-554. DOI: 10.1038/s41586-022-04962-0

2. Hannezo, E., Scheele, C. L., Moad, M., Drogo, N., Heer, R., Sampogna, R. V., ... & van Rheenen. J, Simons, B. D. (2017). A unifying theory of branching morphogenesis. Cell, 171(1), 242-255.

3. Scheele, C. L., Hannezo, E., Muraro, M. J., Zomer, A., Langedijk, N. S., Van Oudenaarden, A., ... & Van Rheenen, J. (2017). Identity and dynamics of mammary stem cells during branching morphogenesis. Nature, 542(7641), 313.

4. Zomer, A., Maynard, C., Verweij, F. J., Kamermans, A., Schäfer, R., Beerling, E., ... & van Rheenen, J. (2015). In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell, 161(5), 1046-1057.

5. Ritsma, L., Ellenbroek, S. I., Zomer, A., Snippert, H. J., de Sauvage, F. J., Simons, B. D., ... & van Rheenen, J. (2014). Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature, 507(7492), 362.

Tassos Perrakis obtained his DPhil in Chemistry from the University of York in 1996, after pre-doctoral research he performed at EMBL Hamburg. He then received an EMBO long-term fellowship, to work at the NKI on DNA mismatch recognition and repair. After two years, he moved as a staff scientist and then a team leader to EMBL Grenoble, where he pursued the development of the ARP/wARP software package for X-ray crystallography, participated in a team that built and commissioned the first µ-diffractometer at ESRF, and pursued his post-doctoral research interests in DNA mismatch repair.

With the change of the millennium, Tassos moved back to the NKI as an independent group leader. Over the last two decades there, his research team pioneered both experimental and computational approaches to X-ray structure determination, like ARP/wARP, a procedure to build protein structure by pattern recognition methods in crystallographic experiments, and PDB-REDO, a decision-making system that allows fully automated “total makeover” of all X-ray structures in the PDB. More recently his interests have shifted towards the application of AI methods to predict protein structures; building on the AlphaFold revolution, his team has built the AlphaFill data bank, adding essential co-factors, metal ions, and other ligands to predicted protein structures. His biochemical research evolves around the structure and function of macromolecules. The group currently focuses on the function and structure of Autotaxin and the LPA signalling axis, contributing new ideas and tools for understanding and utilising this pathway as a target for therapeutic approaches. Concurrently, the team maintains active collaborations that revolve around the role of tubulin modifying and interacting proteins, and how they affect cellular function, and in particular late events in mitosis.

Finally, Tassos has an active involvement in European initiatives being the Coordinator of the “INEXT-Discovery” H2020 program which enables Structural Biology research by providing transnational access to high-end equipment and also promoting collaborative research activities that promote integrative structural biology research approaches. He also has a shared appointment as “ERA chair” in the University of Patras (Greece), transferring knowledge and mentoring a research team in the general area of structural cell biology.

• 2001: EMBO Young Investigator

• 1996: EMBO long-term post-doctoral fellowship

1. algado-Polo F, Borza R., et al, and Perrakis A* Autotaxin facilitates selective LPA receptor signaling. Cell Chemical Biology. Accepted for publication

2. Hekkelman ML, de Vries I, Joosten RP, Perrakis A*. AlphaFill: enriching AlphaFold models with ligands and cofactors. Nature Methods. 2022 Nov 24.

3. Landskron, L, Bak J, Adamopoulos A, Perrakis A*, Brummelkamp TR*, Posttranslational modification of microtubules by the MATCAP detyrosinase, Science 376 (6595)

4. Adamopoulos A, Landskron L, (…) Brummelkamp TR, Perrakis A*. Crystal structure of the tubulin tyrosine carboxypeptidase complex VASH1-SVBP. Nature Structural Molecular Biology. 2019 Jul;26(7):567-570.

5. Sacristan C, (…) A, Perrakis A, Kops GJ. Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nature Cell Biology. 2018 Jul;20(7):800-810.

6. Salgado-Polo F, Fish A (…) Perrakis A*. Lysophosphatidic acid produced by autotaxin acts as an allosteric modulator of its catalytic efficiency. Journal Biological Chemistry. 2018 Sep 14;293(37):14312-14327.

• The AlphaFill databank (alpha-fill.eu) databank and web service for providing ligand structures of predicted protein structures.

• The PDB-REDO (www.pdb-redo.eu) web server and databank for crystallographic structure refinement and validation

• The LAHMA (lahma.pdb-redo.eu) web server for comparing homologuous protein structures.

• The CCD² (ccd.rhpc.nki.nl) web server for protein structure analysis and designing expression constructs.

• The Ramachandran Z-score for protein structure assessment (https://pdb-redo.eu/tortoize).