Mechanisms of chromosome segregation and genome stability. Known among his colleagues and peers as JP, Jeyaprakash is a Professor and Personal Chair of Structural Cell Biology. He completed his PhD on the molecular determinants of carbohydrate-specificities of plant lectins in 2004 at the Indian Institute of Science, Bangalore, under the supervision of Prof. M. Vijayan. After his PhD, JP obtained Alexander von Humboldt and Marie Curie Fellowships to work with Prof. Elena Conti at EMBL-Heidelberg and subsequently at the Max Planck Institute of Biochemistry in Martinsried, Germany, where he became interested in understanding the molecular mechanisms of accurate cell division. In 2012, he established his independent research group, supported by a Wellcome Career Development Fellowship, and was awarded a Wellcome Senior Research Fellowship in 2017. He has recently been awarded an ERC Advanced Grant (2022) and a Wellcome Discovery Award (as Co-Lead; 2024). Since 2023, he has also been leading an ERC-funded lab at the Gene Centre, LMU, Munich, as a visiting professor. Arulanandam (JP) Lab - Gene Centre Munich Jeyaprakash Arulanandam (JP) JP’s lab is interested in understanding the high-resolution mechanistic details of processes that ensure genome stability, with a particular focus on centromere inheritance and chromosome segregation. His significant contributions include the structural and functional characterisation of the Chromosomal Passenger Complex and the Ska complex, key protein assemblies involved in the physical attachment of chromosomes to spindle microtubules during cell division, and the CENP-A loading machinery, critical for maintaining centromeric chromatin identity. Jeyaprakash Arulanandam (JP) Lab Website Lab members Maria Alba Abad, Shiyon Anto, Vimal Das, Anjitha Gireesh, Ana Alves do Vale Marques*, Bethan Medina-Pritchard, Pratiti Nanda, Shashwati Nanda, Paula Sotelo-Parrilla*, Zofia Pukalo, Finn Ritchie, Guangpu Xue*, Zhaoyue Yan, and Huaqing Zeng* (*Munich members) Research Accurate chromosome segregation during cell division is fundamental for organismal survival and human health, as errors can cause aneuploidy, miscarriages, birth defects, and cancer. By integrating biochemical, structural, and cell biological approaches, our lab investigates how cellular machinery ensures faithful partitioning of genetic material to daughter cells in both humans and pathogenic fungi. We focus on the centromere and inner centromere, key chromosome regions governing kinetochore-microtubule interactions and chromatid cohesion, to uncover mechanisms that maintain centromere identity and ensure high-fidelity chromosome segregation and genome stability.Our research addresses pivotal questions:- How is the inner centromere regulatory platform established?- What mechanisms ensure precise chromosome segregation?- How is centromere identity propagated through cell generations?To address these questions, we leverage advanced structural and functional techniques, such as cryo-electron microscopy, X-ray crystallography, crosslinking/mass spectrometry, biochemical, biophysical and cell-based assays. Recent key discoveries:Inner centromere regulatory platform: The Chromosomal Passenger Complex (CPC) is a major regulator of cell division. CPC centromere association is critical for its essential role in ensuring error-free chromosome segregation. Our recent work provided a high-resolution structural basis for CPC centromere association and discovered a novel chromatin protection mechanism of the CPC, demonstrating that perturbing the CPC-chromatin interaction weakens the chromatin association of the CPC and compromises centromeric chromatin integrity, causing mitotic defects (Gireesh et al., EMBO J 2025). Centromere maintenance: Centromere maintenance (replenishment of CENP-A levels at centromeres through active CENP-A deposition) is a tightly controlled process, and its spatio-temporal regulation is achieved by Cdk1 and PLK1 kinases. A mechanistic understanding of how Cdk1 and PLK1 act as licensing factors for the timely deposition of CENP-A remained a critical unanswered question for more than a decade. Our work on the core CENP-A deposition machinery, the Mis18 complex, and its interaction with the PLK1 kinase revealed an essential role for a PLK1-mediated phosphorylation cascade in activating the Mis18 complex. We demonstrated that PLK1-mediated conformational activation of the Mis18 complex is critical for maintaining the correct levels of CENP-A at the centromere (Thamkachy et al., EMBO Rep 2024; Parashara et al., Science 2024). RNA-mediated Regulation of Cell Division: Our recent work on CENP-32, a putative RNA methyltransferase initially identified as a novel mitotic chromosome-associated protein, revealed that it is an active RNA methyltransferase and its activity is critical for maintaining the structural integrity of the mitotic spindle, the chromosome segregation apparatus. We also demonstrated that CENP-32 disease variants observed in patients with a broad spectrum of neurodevelopmental disorders compromise the enzymatic activity and perturb mitotic spindle integrity, thereby revealing CENP-32 as a clinically relevant essential regulator of cell division and proliferation (Dharmadhikari and Abad et al., Nat Commun 2024). Through these efforts, our lab will provide a comprehensive mechanistic understanding of how cells achieve error-free chromosome segregation. We are also keen to discover novel chromosome segregation mechanisms in the evolutionarily divergent, yet clinically highly relevant, human fungal pathogens, including Cryptococcus neoformans. Image Figure LegendA. Overview of ow Cdk1 and PLK1 kinases license CENP-A deposition to ensure maintenance of centromere identity during each round of the Cell Cycle.B. Overview of how CPC-Nucleosome interaction contributes to securing centromeric chromatin integrity, critical for chromosome segregation fidelity. Selected publications Gireesh A*, Abad M*, Nozawa R*, Sotelo-Parrilla P, Dury L, Likhodeeva M, Spanos C, Peralta CC, Rappsilber J, Hopfner K, Wilson M, Vanderlinden W, Hirota T, Jeyaprakash AA§. Nucleosome Interaction of the CPC Secures Centromeric Chromatin Integrity and Chromosome Segregation Fidelity. EMBO J (2025; in press).Dharmadhikari AV* , Abad MA* et al., Davis EE§ , Jeyaprakash AA§ , Liao J§. RNA Methyltransferase SPOUT1/CENP-32 Links Mitotic Spindle Organisation with the Neurodevelopmental Disorder SpADMiSS. Nat Commun (2025) 16:1073Parashara P*, Medina-Pritchard B*, Abad, MA*, Sotelo-Parrilla P*, et al., Jeyaprakash AA§. PLK1-Mediated Phosphorylation Cascade Activates Mis18 Complex to Ensure Centromere Inheritance. Science (2024) 285 (6713): 1098-1104. Doi: https://doi.org/10.1126/science.ado8270 4. Thamkachy R*, Medina-Pritchard, B*, Park, SO*., et al., Jeyaprakash, AA§. Structural Basis for Mis18 Complex Assembly and its Implications for Centromere Maintenance. EMBO Rep (2024) 25(8):3348-3372 This article was published on 2026-04-23
