Nitika Taneja received her MSc in Biotechnology at the Jawaharlal Nehru University, New Delhi, India in 2008. She obtained her PhD in Molecular Life Sciences at the University of Zurich, Switzerland where she studied the propagation of the epigenetic marks that specify centromeres during the process of male meiosis in Drosophila melanogaster. Her work provided the first demonstration of the essential role of a retained histone variant CenH3/Cenp-A in male gametes that is critically important for the embryonic development. These findings were published in Plos Biology, 2012. Due to the fundamental significance of the work, the publication was broadcasted for News & Views in Epigenomics, 2013.
Further pursuing her interests in the chromatin field, Dr. Taneja moved to National Institutes of Health (NIH), USA where she received her post-doctoral training in the National Cancer Institute from April 2013 – April 2017. During this period Dr. Taneja used a Schizosaccharomyces pombe model system to uncover the critical role of chromatin-remodeling factors involved in the inheritance and maintenance of epigenetic marks across cycles of DNA replication. Additionally, she discovered the unique role of the SWI/SNF chromatin remodeling factor Fft3 (Fission FUN30) in maintaining genome stability in yeast where it ensures the proper progression of the DNA replication fork through difficult-to-replicate regions of the genome. These findings were published in Molecular Cell, 2017. The work was further Previewed in Molecular Cell, 2017 and Cell Cycle, 2017 for its distinguished findings. During this period, Dr. Taneja also contributed to other studies demonstrating the role of epigenetics in the maintenance of chromatin organization.
In September 2017, Dr. Taneja joined the Department of Molecular Genetics at Erasmus Medical Center, The Netherlands where her research group focuses on the role of chromatin remodeling and re-organization in suppressing DNA replication stress and on using mouse tumor models to explore the role of chromatin remodelers in counteracting chemo-resistance.
Amongst other fellowship and awards Dr. Taneja has been awarded with the Daniel den Hoed Young Investigator award in December 2017.
Field(s) of expertise
Chromatin Remodeling and Replication
Our lab aims to understand the mechanistic link between chromatin remodeling pathways and the stability of DNA replication machinery to proper chromatin organization and concomitant genome stability. Through our research aimed at targeting chromatin remodelers, we will obtain a mechanistic understanding of the cellular processes that render cells sensitive or resistant to commonly used chemotherapeutic treatments. We study chromatin remodeling and DNA replication using multiple model systems that include cultured human cells, mouse tumor models, 3D-organoids and fruit flies. We genetically manipulate and study these model systems using a combination of high-throughput cell biology, genomic and biochemistry techniques to discover the underlying mechanisms in normal cells that counteract replicative stress and thus avert tumorigenesis.
Chromatin remodeling is the dynamic alteration of chromatin architecture that ensures a highly regulated cell-cycle progression, and involves processes such as DNA replication, DNA repair and chromosome segregation. The fact that perturbations in chromatin architecture often underlie tumorigenesis suggests that chromatin remodeling factors normally provide a tumor-suppressor function by maintaining genome integrity. Chromatin associated factors involved in the modulation of the genomic and epigenomic profile of cancer cells can be targeted by using agents that enhance cellular replicative stress. Such stress-enhancing agents can potentially overcome cancer chemoresistance and improve existing chemotherapeutic regimens.
Using human cell lines, a mouse model system, and 3-D organoid cultures in combination with proteomics, fluorescence microscopy and high-throughput genome sequencing techniques, we are probing the role of chromatin remodeling in the suppression of replication stress and determining its significance in the prevention of tumorigenesis.
Our lab’s focus is to investigate the mechanistic link between remodeling of chromatin and execution of DNA replication to the maintenance of proper genome architecture. We are further interested in identifying those processes that are critically involved in the suppression of tumorigenesis. The question marks highlight the processes or links of particular interest.
Mechanisms of chromatin remodeling in counteracting replicative stress and tumorigenesis
The overall aim of our group is to detail the role of chromatin remodelers in the maintenance of genome stability and in the development chemo-resistance in tumor cells.
Key areas of focus include:
- Analysis of underlying structural barriers that impede replication fork progression and thus thwart the mechanisms of DNA replication-linked genome stabilization
- Analysis of the 3-D architecture of the genome
- Identification of factors counteracting tumorigenesis and chemotherapeutic resistance
We are examining the mechanistic role of our recently identified novel replication fork associated chromatin remodeling factors in preventing the formation of RNA-DNA hybrids (R-loops) and in promoting replication fork stability. We are also investigating the role of replication stress in instigating a re-organization of chromatin architecture that can potentially allow tumor cells to adapt and become chemo-resistant. We continue to seek novel chromatin factors involved in the sensitivity to replication stress induced by chemotherapeutic treatments. To this end we are preparing to perform a unique unbiased genetic screen and to use a novel high-throughput image-based screening assay to identify the factors that relieve replicative stress by resolving structural barriers that exist in the vicinity of the replication fork. Finally, we will test the clinical significance of selected candidate factors in mouse tumor models to study their direct effects on tumor regression.
Taneja N* and Grewal SI. Shushing Histone Turnover: It's Fun Protecting the Genome and Epigenome. (Cell Cycle 2017: p.1-2)
* Corresponding author
Taneja N, Zofall M, Balachandran V, Thillainadesan G, Sugiyama T, Wheeler D, Zhou M, Grewal SI. SNF2 Family Protein Fft3 Suppresses Nucleosome Turnover to Promote Epigenetic Inheritance and Proper Replication. (Molecular Cell2017, 66:50-62)
This article was selected for Preview in Molecular Cell. Fortuny A and Polo SE. Genome and Epigenome Maintenance by Keeping Histone Turnover in Check. (Molecular Cell 2017, 66:3-4)
Mizuguchi T, Taneja N, Fudenberg G, Belton JM, FitzGerald P, Mirny LA, Dekker J and Grewal SI. Sheltrin Components Mediates Genome Reorganization in Response to Replication Stress. (PNAS 2017, 114(21):5479-5484)
Mizuguchi T, Fudenberg G, Mehta S, Belton JM, Taneja N, Folco HD, FitzGerald P, Dekker J, Mirny L, Barrowman J, Grewal SI. Cohesin-Dependent Globules and Heterochromatin Shape 3D Genome Architecture in S. pombe. (Nature 2014, 516:432-5)
Lee NN, Chalamcharla VR, Reyes-Turcu F, Mehta S, Zofall M, Balachandran V, Dhakshnamoorthy J, Taneja N, Yamanaka S, Zhou M, Grewal SI. Mtr4-like Protein Coordinates Nuclear RNA Processing for Heterochromatin Assembly and for Telomere Maintenance. (Cell 2013, 155:1061-74)
Raychaudhuri N*, Dubruille R, Orsi GA, Bagheri HC, Loppin B, Lehner CF. Transgenerational Propagation and Quantitative Maintenance of Paternal Centromeres Depends on Cid/Cenp-A Presence in Drosophila Sperm. (Plos Biology 2012, 10(12): e1001434)
* Raychaudhuri N. mentioned here is Taneja N.
This article was selected for News & Views in Epigenomics. Shiota H, Goudarzi A, Rousseaux S, Khochbin S. Transgenerational inheritance of chromatin states. (Epigenomics 2013, 5:121-122) IF 4.54