Hubrecht Institute

Marvin Tanenbaum received his PhD (Cum Laude) in 2010 from Utrecht University for his work on cell division in the group of Prof. René Medema. During his PhD work, Marvin used live-cell microscopy to study the molecular mechanism of chromosome segregation during cell division. After obtaining his PhD, he received KWF and EMBO fellowships to perform his postdoctoral research in the group of Prof. Ron Vale at UCSF in the United States. As a postdoc, Marvin developed a keen interest in studying the control mechanisms and dynamics of gene expression in single cells, focusing on gene expression control during the cell cycle. He pioneered several new techniques using protein engineering that enabled direct observation of single protein molecules in action, and developed methods to observe gene expression in single living cells by fluorescence microscopy. He also developed a technique to modulate the activity of individual genes in single cells. In 2015, he became a group leader at the Hubrecht Institute. His group studies the molecular mechanisms of gene expression control at the single-molecule level, both for humans and in viruses, and aims to understand how control of gene expression affects important cellular decisions.

• Elected EMBO member in 2022

• Recipient of an ERC Consolidator grant in 2022

• Prix Galien Excellence COVID-19 Award in 2021

• EMBO young investigator (YIP) in 2019

• Recipient of a VIDI grant in 2018

• Howard Hughes Medical Institute (HHMI) International Research Scholar in 2017

• Recipient of an ERC Starting grant in 2015

• Recipient of EMBO Long-term fellowship in 2011

• Recipient of a Dutch Cancer Society postdoctoral fellowship in 2011

• NVMO Oncology Thesis Award in 2011

• Utrecht University Thesis Prize in 2011

1. Boersma S, Rabouw HH, Bruurs LJM, [...] van Kuppeveld F, Tanenbaum ME (2020). Translation and Replication Dynamics of Single RNA Viruses. Cell, 183, 1–16.

2. Hoek TA, Khuperkar D, Lindeboom RGH, [...] Tanenbaum ME (2019). Single-molecule imaging uncovers rules governing nonsense-mediated mRNA decay. Molecular Cell, 75(2), 324-339.

3. Boersma S, Khuperkar D, Verhagen BMP, [...] Tanenbaum ME (2019). Multi-color single-molecule imaging uncovers extensive heterogeneity in mRNA decoding. Cell, 178(2), 458-472.

4. Yan, X., Hoek, T. A., Vale, R. D., & Tanenbaum, M. E. (2016). Dynamics of translation of single mRNA molecules in vivo. Cell, 165(4), 976-989.

5. Ruijtenberg S, Sonneveld S, Cui TJ, [...] Tanenbaum ME (2020). mRNA structural dynamics shape Argonaute-target interactions. Nat Struct Mol Biol, 28(6), 533.

6. Krijger PHL, Hoek TA, [...] de Laat W, Tanenbaum ME (2021). A public-private partnership model for COVID-19 diagnostics. Nat Biotechnol. 39(10), 1182-1184.

Danny Sahtoe performed his PhD research in the lab of Prof. Titia Sixma at the Netherlands Cancer Institute where the studied the atomic 3D structure of protein complexes involved in gene regulation. After his PhD he moved to the computational protein design lab of Prof. David Baker at the Institute of Protein Design in Seattle, USA. Here he developed novel approaches to design synthetic protein-protein interactions resulting in the design of artificial multiprotein complexes, amyloid fibril inhibiting proteins and small proteins for use in blood-brain-barrier traversal. In 2023 he started his own lab at the Hubrecht Institute where he uses protein design approaches to create novel research tools and study fundamental biological processes.

• Recipient of a NWO-VIDI grant (2023)

• Recipient of a Washington Research Foundation Innovation Fellowship (2015)

• Recipient of a EMBO long term fellowship (2015)

1. Sahtoe, D.D., Andrzejewska, E.A., Han, H.L. et al. Design of amyloidogenic peptide traps. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-024-01578-5

2. Sahtoe, D. D.; Coscia, A.; Mustafaoglu, N.; Miller, L. M.; Olal, D.; Vulovic, I.; Yu, T.-Y.; Goreshnik, I.; Lin, Y.-R.; Clark, L.; Busch, F.; Stewart, L.; Wysocki, V. H.; Ingber, D. E.; Abraham, J.; Baker, D. Transferrin Receptor Targeting by de Novo Sheet Extension. Proc. Natl. Acad. Sci. 2021, 118 (17), e2021569118. https://doi.org/10.1073/pnas.2021569118.

3. Sahtoe, D. D.; Praetorius, F.; Courbet, A.; Hsia, Y.; Wicky, B. I. M.; Edman, N. I.; Miller, L. M.; Timmermans, B. J. R.; Decarreau, J.; Morris, H. M.; Kang, A.; Bera, A. K.; Baker, D. Reconfigurable Asymmetric Protein Assemblies through Implicit Negative Design. Science 2022, 375 (6578), eabj7662. https://doi.org/10.1126/science.abj7662.

4. Sahtoe, D. D.; Andrzejewska, E. A.; Han, H. L.; Rennella, E.; Schneider, M. M.; Meisl, G.; Ahlrichs, M.; Decarreau, J.; Nguyen, H.; Kang, A.; Levine, P.; Lamb, M.; Li, X.; Bera, A. K.; Kay, L. E.; Knowles, T. P. J.; Baker, D. Design of Amyloidogenic Peptide Traps. bioRxiv January 13, 2023, p 2023.01.13.523785. https://doi.org/10.1101/2023.01.13.523785.

5. Sahtoe, D. D.; van Dijk, W. J.; Ekkebus, R.; Ovaa, H.; Sixma, T. K. BAP1/ASXL1 Recruitment and Activation for H2A Deubiquitination. Nat. Commun.2016, 7 (1), 10292. https://doi.org/10.1038/ncomms10292.

6. Sahtoe, D. D.; van Dijk, W. J.; El Oualid, F.; Ekkebus, R.; Ovaa, H.; Sixma, T. K. Mechanism of UCH-L5 Activation and Inhibition by DEUBAD Domains in RPN13 and INO80G. Mol. Cell 2015, 57 (5), 887–900. https://doi.org/10.1016/j.molcel.2014.12.039.

• 1999 Member European Molecular Biology Organisation (EMBO)

• 2000 Member of the Royal Netherlands Academy of Sciences (KNAW)

• 2009 Member of the Academia Europaea

• 2012 Member of the American Academy of Arts and Sciences

• 2012 Member of the ‘Koninklijke Hollandsche Maatschappij der Wetenschappen’ (Royal Netherlands Society of Sciences and Humanities)

• 2014 International member of the National Academy of Sciences of the USA

• 2016 Member of the Academie des Sciences de I'Institut de France

• 2017 Member of the Orden Pour le Mérite für Wissenschaften und Künste, Germany

• 2019 Member of the New York Academy of Sciences, New York

• 2019 Foreign Member of the Royal Society of London

• 2019 Honorary Fellowship of the Royal Society of Edinburgh, Scotland’s National Academy of Science and Letters

• 2022: Ammodo Science Award

• 2022: Taobuk Da Vinci Award

• 2021: Pezcoller Foundation-AACR International Award

• 2019: Citation Laureate, Clarivate/Web of Science Group

• 2019: Keio Medical Science Prize, Tokyo, Japan

• 2018: Academia Europaea Erasmus Medal, Barcelona, Spain

• 2017: Großes Verdienstkreuz mit Stern, Germany

• 2017: Princess Takamatsu Award of Merit, Tokyo

• 2016: The Ilse & Helmut Wachter award, Hamburg, Germany

• 2016: Swammerdam medaille (Amsterdam)

• 2016: The Körber European Science Prize, Germany

• 2016: Kazemi Award for Research Excellence in Bio-Medicine

• 2016: the Academy Professor Prize of the Royal Netherlands Academy

• 2015: ISSCR-McEwen Award for Innovation

• 2014: National Icon of the Netherlands

• 2014: Struyvenberg European Society for Clinical Investigation (ESCI) medal

• 2014: Fellow of the AACR Academy

• 2014: TEFAF Oncology Chair 2014, Maastricht

• 2014: Massachusetts General Hospital Award in Cancer Research

• 2013: The Breakthrough Prize in Life Sciences

• 2012: Knight in the Order of the Nederlands' Lion

• 2012: The Heineken Prize for Medicine

• 2012: William Beaumont prize of the American Gastroenterology Association

• 2012: Association pour la Recherche sur le Cancer (ARC) Léopold Griffuel Prize, Paris

• 2011: Kolff prize, Amsterdam

• 2011: The Ernst Jung Medical Award, Germany

• 2010: The United European Gastroenterology Federation (UEGF) Research Prize

• 2009: The Queen Wilhelmina Dutch Cancer Society Award, Amsterdam

• 2008: Meyenburg Cancer Research Award, Germany

• 2008: Josephine Nefkens Prize for Cancer Research (Erasmus MC, Rotterdam)

• 2006: Rabbi Shai Shacknai Memorial Prize for Immunology and Cancer Research, Jerusalem

• 2005: Katharine Berkan Judd Award, New York

• 2005: the French honor of “Chevalier de la Legion d'Honneur”

• 2005: the Science and Society Prize, Amsterdam

• 2004: Louis-Jeantet Prize for Medicine, Geneva, Switzerland

• 2001: Spinoza Award of the Netherlands Reserach Council (NWO)

• 2001: Award from the European Society for Clinical Investigation

• 2000: Catharijne-prize for medical research

1. Barker, N., Van Es, J. H., Kuipers, J., Kujala, P., Van Den Born, M., Cozijnsen, M., ... & Clevers, H. (2007). Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature, 449(7165), 1003.

2. Drost, J., Van Jaarsveld, R. H., Ponsioen, B., Zimberlin, C., Van Boxtel, R., Buijs, A., ... & Clevers, H. (2015). Sequential cancer mutations in cultured human intestinal stem cells. Nature, 521(7550), 43.

3. Huch, M., Gehart, H., Van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M. M., ... & Clevers, H. (2015). Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell, 160(1), 299-312.

4. Sato, T., Vries, R. G., Snippert, H. J., Van De Wetering, M., Barker, N., Stange, D. E., ... & Clevers, H. (2009). Single Lgr5 stem cells build crypt–villus structures in vitro without a mesenchymal niche. Nature, 459(7244), 262.

5. Van de Wetering, M., Francies, H. E., Francis, J. M., Bounova, G., Iorio, F., Pronk, A., ... & Clevers, H. (2015). Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell, 161(4), 933-945.

Prof. dr. ir. Alexander van Oudenaarden is director and group leader at the Hubrecht Institute (KNAW) and professor of quantitative biology of gene regulation at the Faculty of Science and the Faculty of Medicine at Utrecht University. His research group works with advanced (light) microscopy and sequencing technologies in order to study individual cells. Van Oudenaarden studied materials science and physics at Delft, where he also obtained his PhD in solid state physics. As a postdoc he worked at Stanford University collaborating with Steven Boxer and Julie Theriot. He was professor of physics and biology at the Massachusetts Institute of Technology (MIT). In 2012 he moved to the Hubrecht Institute after 15 years in the USA. His group combines techniques – in part developed by themselves – from developmental biology, molecular biology, physics, mathematics and computer science. He was awarded the 2011 and 2016 ERC Advanced Investigator grant and in 2017 van Oudenaarden won the Spinoza Award.

• 2017: Dutch Organization for Scientific Research (NWO) Spinoza Award

• 2017: EMBO member

• 2017: European Research Council (ERC) Advanced Grant

• 2015: Member of Koninklijke Hollandsche Maatschappij der Wetenschappen (KHMW)

• 2014: Member of the Royal Netherlands Academy of Arts and Sciences (KNAW)

• 2012: European Research Council (ERC) Advanced Grant

• 2012: Dutch Organization for Scientific Research (NWO) Vici Award

• 2008: NIH Director’s Pioneer Award

• 2008: Guggenheim Fellow

• 2007: School of Science Prize for Excellence in Graduate Teaching

• 2001: Keck Career Development Professor in Biomedical Engineering

• 2001: Alfred Sloan Research Fellow

• 2001: NSF CAREER award

• 2000: Edgerly Science Partnership Award

• 1998: Andries Miedema Award for best Ph.D.-research in the field of condensed matter physics in the Netherlands, awarded every other year by Fundamental Research on Matter (FOM).

• 1998: Dutch Organization for Scientific Research (NWO) TALENT stipendium.

• 1998: Ph.D. Applied Physics, cum laude.

• 1994: Award for best undergraduate research in Materials Science, yearly award by Delft University of Technology.

• 1993: M.S. Materials Science and Engineering, cum laude.

1. Grün, D., Lyubimova, A., Kester, L., Wiebrands, K., Basak, O., Sasaki, N., ... & van Oudenaarden, A. (2015). Single-cell mRNA sequencing reveals rare intestinal cell types. Nature, 525(7568), 251.

2. Schmiedel, J. M., Klemm, S. L., Zheng, Y., Sahay, A., Blüthgen, N., Marks, D. S., & van Oudenaarden, A. (2015). MicroRNA control of protein expression noise. Science, 348(6230), 128-132.

3. Junker, J. P., Noël, E. S., Guryev, V., Peterson, K. A., Shah, G., Huisken, J., ... & van Oudenaarden, A. (2014). Genome-wide RNA tomography in the zebrafish embryo. Cell, 159(3), 662-675.

4. Neuert, G., Munsky, B., Tan, R. Z., Teytelman, L., Khammash, M., & van Oudenaarden, A. (2013). Systematic identification of signal-activated stochastic gene regulation. Science, 339(6119), 584-587.

5. Ji, N., Middelkoop, T. C., Mentink, R. A., Betist, M. C., Tonegawa, S., Mooijman, D., ... & van Oudenaarden, A. (2013). Feedback control of gene expression variability in the Caenorhabditis elegans Wnt pathway. Cell, 155(4), 869-880.

Geert Kops obtained his PhD cum laude in 2001 from Utrecht University for his investigations into the oncogenic PI3K-PKB/Akt–FOXO pathway and its role in cellular proliferation. He then pursued postdoctoral studies in the lab of Don Cleveland at the Ludwig Institute for Cancer Research in La Jolla, USA, where he investigated molecular mechanisms of chromosome segregation. Geert returned to the Netherlands in 2005 as a group leader at UMC Utrecht, where he became Professor of Molecular Tumor Cell Biology in 2011. He was the head of the laboratory for Medical Oncology from 2011 to 2014, and has been the Scientific Director of Oncode Institute since 2018.

After a research sabbatical at the Fred Hutch Cancer Research Center in Seattle, USA, Geert joined the Hubrecht Institute in October 2015. His primary research interests include molecular mechanisms of chromosome segregation, evolution of cell division processes and the causes and consequences of chromosomal instability in cancer. Geert is the recipient of the KNCV gold medal 2014, the NVBMB prize 2004, and the Von Freyburg medal in 2006, and was elected to the Young Academy of Europe (YAE) in 2013. He was awarded NWO-Vidi and Vici grants in 2006 and 2013, respectively, ERC Starting and Synergy grants from the European Research Council in 2009 and 2019, respectively, and he is co-lead of the NWO Gravitation project IMAGINE!. Geert co-developed ‘De Gemene Deler’, a teaching module for high schools about molecular mechanisms, cells and cancer.

• 2022: NWO Gravitation award

• 2019: Cozzarelli Prize for PNAS paper of the year in Class II (Biological Sciences)

• 2016: PhD supervisor of the year (runner-up), Utrecht Life Sciences

• 2014: Gold Medal of the Royal Dutch Chemistry Society (KNCV)

• 2013: NWO-Vici grant

• 2013: Best Masters course of the Utrecht Graduate School of Life Sciences

• 2013: Elected to the Young Academy of Europe (YAE)

• 2009: ERC StG/CoG (prior to separation into StG and CoG)

• 2006: NWO-Vidi grant

• 2006: Von Freyburg Medal (Catharijne Foundation)

• 2004: NVBMB prize (Netherlands Society for Biochemistry and Molecular Biology)

• 2001: KWF (Dutch Cancer Society) preclinical- and fundamental research fellowship

• 2000: Young talent award, UMC Utrecht

1. Klaasen SJ, Truong MA, van Jaarsveld RH, Koprivec I, Štimac V, de Vries SG, Risteski P, Kodba S, Vukušić K, de Luca KL, Marques JF, Gerrits EM, Bakker B, Foijer F, Kind J, Tolić IM, Lens SMA, Kops GJPL. Nuclear chromosome locations dictate segregation error frequencies. Nature 607 (2022), 604-609

2. Hoevenaar W, Janssen A, Quirindongo AI, Ma H, Klaasen S, Teixeira A, Offerhaus GJA, Medema RH, Kops GJPL*, Jelluma N*. Degree and site of chromosomal instability define its oncogenic potential. Nat Commun 11 (2020), 1501. *joint senior authors

3. Bolhaqueiro ACF, Ponsioen B, Bakker B, Klaasen SJ, Kucukkose E, Van Jaarsveld RH, Vivié J, Verlaan-Klink I, Hami N, Spierings DCJ, Sasaki N, Dutta D, Boi SF, Vries RGJ, Lansdorp PM, Van de Wetering M, Van Oudenaarden A, Clevers H, Kranenburg O, Foijer F, Snippert HGJ, Kops GJPL. Ongoing chromosomal instability and karyotype evolution in human colorectal cancer organoids. Nat Genet. 51 (2019), 824-834.

4. Sacristan C, Ahmad MAD, Keller J, Fermie J, Groenewold V, Tromer E, Fish A, Melero R, Carazo JM, Klumperman J, Musacchio A, Perrakis A, Kops GJPL. Dynamic kinetochore size regulation promotes microtubule capture and chromosome biorientation in mitosis. Nat Cell Biol 20 (2018), 800-810.

5. Hiruma Y, Sacristan C, Pachis ST, Adamopoulos A, Kuijt T, Ubbink M, Von Castelmur E, Perrakis A, Kops GJPL. (2015). Competition between MPS1 and microtubules at kinetochores regulates spindle checkpoint signaling. Science, 348 (6240), 1264-1267.

Puck Knipscheer has been interested in understanding the molecular details of biological processes since her PhD (2007) at the Netherlands Cancer Institute with Prof. Titia Sixma. Here she used X-ray crystallography and biochemistry to investigate posttranslational modification by the ubiquitin-like modifier SUMO. During her postdoc in the laboratory of Johannes Walter at Harvard Medical School she started to study genome maintenance.

She contributed to the development of a unique Xenopus egg extract based system that allows the repair of highly toxic DNA interstrand crosslinks (ICLs) under physiological conditions in vitro. Subsequently, she used this system to elucidate the role of the Fanconi anemia protein FANCD2 and showed for the first time how the activated Fanconi anemia pathway acts in a specific step in ICL repair.

In 2011 she started her own laboratory at the Hubrecht Institute in Utrecht where she continued her investigations into this poorly understood DNA repair pathway. She identified the long sought endonuclease that unhooks an ICL during repair. In addition, she developed a system to study G4 structure unwinding under physiologically relevant conditions and found a direct role for the helicase FANCJ. She currently continues to use this system to investigate the mechanisms by which stable secondary DNA structures are resolved during DNA replication.

• 2021: ERC consolidator grant

• 2016: KWF project grant

• 2011: NWO-Vidi grant

• 2010: Heineken Young Scientist Award for Biochemistry and Biophysics, Royal Netherlands Academy of Arts and Sciences (KNAW)

• 2007: KWF (Dutch Cancer Society) preclinical- and fundamental research fellowship

1. Koichi Sato, Nerea Martin-Pintado, Harm Post, Maarten Altelaar, and Puck Knipscheer (2021). Multistep mechanism of G-quadruplex resolution during DNA replication. Science Advances, 7(39).

2. Hodskinson, M.R. *, Bolner, A.*, Sato, K., Kamimae-Lanning, A.N., Rooijers, K., Witte, M., Mahesh, M.,Silhan, J., Petek, M., Williams, D.M., Kind, J., Chin, J., Patel, K.J.^#, and Knipscheer, P.^#(2020). Alcohol-derived DNA interstrand crosslinks are repaired by two distinct mechanisms. Nature, 579(7800);603-608.

3. Daisy Klein Douwel, Wouter Hoogenboom, Rick Boonen and Puck Knipscheer(2017). Recruitment and positioning determine the specific role of the XPF-ERCC1 endonuclease in interstrand crosslink repair. EMBO J, 36(14):2034-46.

4. Klein Douwel, D.⁺, Boonen, R.A.C.M.⁺, Long, D.T., Szypowska, A.A., Räschle, M., Walter, J.C., and Knipscheer P. (2014). XPF-ERCC1 acts in unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Mol Cell. 54(3):460-71.

5. Knipscheer, P., Räschle, M., Smogorzewska, A., Enoiu, M., Ho, T.V., Schärer, O.D., Elledge, S.J., and Walter, J.C. (2009). The Fanconi anemia pathway promotes replication-dependent DNA interstrand crosslink repair. Science 326:1698-1701.

Jop Kind received his PhD from the Radboud University Nijmegen in 2008 for his work on chromatin and gene expression performed at the EMBL Heidelberg. He subsequently joined the Netherlands Cancer Institute for his postdoctoral training, where he developed novel methods to study nuclear organization in individual cells. For this work he received the prestigious Antoni van Leeuwenhoek (NKI) and John Kendrew awards (EMBL). In October 2014, he established his research group at the Hubrecht Institute and became a senior group leader in 2019 and a professor of single cell epigenomics at the Radboud University in 2021. His research is supported by an ERC Starting (2016) and Consolidator grant (2021) a NWO Vidi (2016) and his group is a member of two recent consortia grants NWO-PSIDER (2021) and NWO-XL (2022).

• 2016: Sir John Kendrew Award

• 2015: Antoni van Leeuwenhoek Award

1. Rang FJ, de Luca KL, de Vries SS, Valdes-Quezada C, Boele E, Nguyen PD, Guerreiro I, Sato Y, Kimura H, BakkersJ, Kind J. Single-cell profiling of transcriptome and histone modifications with EpiDamID. Mol Cell. May19;82(10):1956-1970.e14 (2022).

2. Rullens PMJ, Kind J.Attach and stretch: Emerging roles for genome-lamina contacts in shaping the 3Dgenome. Curr Opin Cell Biol. Jun;70:51-57 (2021).

3. Markodimitraki CM, Rang F, Rooijers K, de Vries SS, Chialastri A, de Luca KL, Lochs SJA, Mooijman D, Dey SS and Kind J. Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells with scDam&T. Nature Protocols 15:1922-1952 (2020).

4. Borsos M, Perricone SM, Schauer T, Pontabry J, de Luca KL, de Vries SS, Ruiz-Morales ER, Torres- Padilla ME and Kind J. Genome-lamina interactions are established de novo in the early mouse embryo. Nature 569:729-733 (2019).

5. Rooijers K, Markodimitraki CM, Rang F, de Vries SS, Chialastri A, de Luca KL, Mooijman D, Dey SS and Kind J. Simultaneous quantification of protein-DNA contacts and transcriptomes in single cells. Nature Biotechnology 37:766-772 (2019).