Our Focus
Chemoresistance poses a significant challenge in cancer treatment, allowing cancer cells to continue proliferating despite chemotherapy-induced replication stress and DNA damage. My research focuses on investigating the underlying molecular mechanisms that modify chromatin at replication forks, enabling cells to cope with replication stress. My expertise lies in chromatin biology, replication stress, and chemoresistance.
In my lab, we have developed novel tools and technologies to study chromatin dynamics at replication forks, ranging from single-molecule chromatin fibers to kb-resolution analysis of nascent genome under replication stress through high-throughput genomics. Using various mammalian systems, including tumour models, we aim to uncover how chromatin dynamics and histone modifiers regulate replication fork stability and genome integrity during stress and how these mechanisms contribute to chemotherapy resistance in cancer cells.
Main Research Questions:
- How do local histone/RNA modifications at replication forks drive spatial chromatin reorganization, including chromatin loop stabilization and phase separation, to promote replication fork stability under replication stress?
- How do differences in spatial chromatin organization, including chromatin loop stabilization and phase separation, distinguish chemo resistant cancer cells from chemo sensitive ones and which key factors enable this adaptation, offering potential targets to resensitize chemo resistant tumours effectively?
About Nitika Taneja
Nitika Taneja
My Research
Nitika Taneja is an Associate Professor and Principal Investigator at Erasmus MC, focusing her research on understanding the intricate molecular mechanisms of chromatin remodeling during DNA replication and replication stress to maintain genome stability. During her PhD work under Prof. Christian Lehner at the University of Zurich, Switzerland, she demonstrated the transgenerational propagation of histones/epigenetic marks from fathers to progeny. This research highlighted the essential role of a retained centromere histone variant in male gametes, inherited during the first zygotic DNA replication, crucial for embryonic development.
During her postdoctoral tenure at the National Cancer Institute, NIH, USA, with Dr. Shiv Grewal, Dr. Taneja designed specialized genetic screens to identify factors critical for genome and epigenome stability during DNA replication. In 2018, she established her research program at the Department of Molecular Genetics, Erasmus MC, Netherlands. Her research program explores the role of 3-D chromatin architecture in mediating replication fork stability under replication stress. By uncovering these connections and identifying key factors, her work unveils potential mechanisms and strategies to sensitize cancer cells to chemotherapy. Her team also develops innovative tools and technologies to investigate transient chromatin changes at replication fork sites and genome-wide chromatin spatial reorganization in response to replication stress.
Awards
2023: ERC starting grant
2023: NWO - Aspasia premium award
2022: NWO - VIDI Talent award
2021: NWO - Women in STEM Incentive grant
2021: Convergence Health & Technology: Open Mind Call
2020: Erasmus+ grant
2018: Daniel den Hoed Stichting Foundation- Young Investigator Award
2017: Fellows Award for Research Excellence
2012: Sri AsaNanda Young Scientific Talent Award
Key Publications
Lo CSY, Taneja N*, Ray Chaudhuri A*. Enhancing quantitative imaging to study DNA damage response: A guide to automated liquid handling and imaging. (DNA repair 2024, DOI: 10.1016/j.dnarep.2024.103769)
Uruci, Hoitsma, Solér-Oliva, Bayona-Feliu, Gaggioli, García-Rubio, Lo, Bakker, Marinello, Manolika, Capranico, Luijsterburg, Luger *, Aguilera *, Taneja*. SMARCAD1 Regulates R-Loops at Active Replication Forks Linked to Cancer Mutation Hotspots. (BioRxiv2024.09.13.612941)
Davó-Martínez C, Helfricht A, Ribeiro-Silva C, Raams A, Tresini M, Uruci S, van Cappellen WA, Taneja N, Demmers JAA, Pines A, Theil AF, Vermeulen W, Lans W. Different SWI/SNF complexes coordinately promote R-loop- and RAD52-dependent transcription-coupled homologous recombination. (Nucleic Acid Research 2023, DOI: 10.1093/nar/gkad609)
Gaggioli V, Lo CSY, Reverón-Gómez N, Jasencakova Z, Domenech H, Nguyen H, Sidoli S, Tvardovskiy A, Uruci S, Slotman JA, Chai Y, Goncalves JG, Manolika EM, Jensen ON, Wheeler D, Sridharan S, Chakraborty S, Demmers J, Kanaar R, Groth A, Taneja N*. Dynamic de novo heterochromatin assembly and disassembly at replication forks ensure fork stability. (Nature Cell Biology 2023, DOI: 10.1038/s41556-023-01167-z)
Chakrabarty S, Quiros-Solano, Kuijten M, Haspels B, Mallya S, Lo CSY, Othman A, Gaio N, Odijk H, van de Ven, de Ridder, Weerden W, Jonkers J, Dekker R, Taneja N, Kanaar R, van Gent D. A microfluidic cancer-on-chip platform predicts drug response using organotypic tumor slice culture. (Cancer Research 2022, PMID: 34872965)
Uruci S, Lo CSY, Wheeler D, Taneja N*. R-Loops and Its Chro-Mates: The Strange Case of Dr. Jekyll and Mr. Hyde. (IJMS 2021, PMID: 34445553)
Lo CSY, van Toorn M, Gaggioli V, Dias MP, Zhu Y, Manolika EM, Zhao W, van der Does M, Goncalves JG, van Royen M, French P, Demmers J, Smal I, Lans H, Wheeler D, Jonkers J, Ray Chaudhuri A, Marteijn JA, Taneja N*. SMARCAD1 Mediated Active Replication Fork Stability Maintains Genome Integrity. (Science Advances 2021, PMID: 33952518)
* corresponding author
Members
| Nitika Taneja Oncode Investigator | Ashutosh Choudhury PhD student | Collin Bakker PhD student |
| Jialin Li PhD | Joanna Paulson PhD student | Kaustav Sengupta Postdoc |
| Vincent Gaggioli PostDoc | Xingde Wang PhD |