Aaran Vijayakumaran
Postdoctoral Scholar, Biochemistry
Bio
Aaran Vijayakumaran, PhD is a Postdoctoral Scholar at Stanford University School of Medicine, where he researches the cell biology of inherited Parkinson’s Disease in the Department of Biochemistry under Professor Suzanne Pfeffer.
He completed his PhD at the University of Cambridge, applying volumetric electron microscopy and deep-learning based image segmentation to generate the first nanoscale map of the human airway epithelium. His doctoral work revealed how cellular architecture and metabolism remodel during differentiation, with a particular focus on the motile cilia, their rootlets, and their structural contacts with mitochondria and the consequences for mitochondrial metabolism. Beyond research, Aaran is active in the biotech and innovation ecosystem. He was awarded a scholarship to join EnterpriseTECH at Cambridge Judge Business School, served as an Investment Fellow Intern at Syncona, and worked as a Venture Builder Intern at Cambridge Future Tech and OmniBuds, a medical device startup. In these roles, he contributed to early-stage strategy, clinical trial planning, and commercial development.
Professional Education
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Doctor of Philosophy, University of Cambridge, Toxicology (2025)
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Masters of Research, King's College London, Translational Cancer Medicine (2021)
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Bachelor of Science, University of Nottingham School of Medicine, Physiology (2020)
All Publications
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3D nanoscale reconstruction of human airway multiciliogenesis reveals cellular architecture remodeling and cilia-mitochondria link via rootlets.
Cell reports
2026; 45 (7): 117714
Abstract
A central challenge in single-cell biology is understanding how molecular programs drive changes in cellular architecture that enable specialized function. A striking example of cellular remodeling is the differentiation of airway stem cells into the respiratory multiciliated epithelium, a protective tissue barrier that clears inhaled pathogens and particulate matter. Here, we present its first three-dimensional nanometer-scale reconstruction, revealing coordinated changes in cellular organization, organelle topology, and inter-organelle contacts during multiciliogenesis. We uncover a structural and functional association between motile cilia and mitochondria mediated by rootlets, striated cytoskeletal fibers that remain poorly characterized in human airway multiciliated cells. Rootlets connect to basal bodies through a multiprotein linker containing the uncharacterized rootletin/CROCC homolog CROCC2, oscillate at frequencies comparable to ciliary beating, promote basal body alignment, and when lost, reduce maximal mitochondrial respiratory capacity. Altogether, this work integrates structural, dynamic, and functional analyses to elucidate mechanisms underlying airway mucociliary defense.
View details for DOI 10.1016/j.celrep.2026.117714
View details for PubMedID 42485185
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Uncovering structural themes across cilia microtubule inner proteins with implications for human cilia function.
Nature communications
2024; 15 (1): 2687
Abstract
Centrosomes and cilia are microtubule-based superstructures vital for cell division, signaling, and motility. The once thought hollow lumen of their microtubule core structures was recently found to hold a rich meshwork of microtubule inner proteins (MIPs). To address the outstanding question of how distinct MIPs evolved to recognize microtubule inner surfaces, we applied computational sequence analyses, structure predictions, and experimental validation to uncover evolutionarily conserved microtubule- and MIP-binding modules named NWE, SNYG, and ELLEn, and PYG and GFG-repeat by their signature motifs. These modules intermix with MT-binding DM10-modules and Mn-repeats in 24 Chlamydomonas and 33 human proteins. The modules molecular characteristics provided keys to identify elusive cross-species homologs, hitherto unknown human MIP candidates, and functional properties for seven protein subfamilies, including the microtubule seam-binding NWE and ELLEn families. Our work defines structural innovations that underpin centriole and axoneme assembly and demonstrates that MIPs co-evolved with centrosomes and cilia.
View details for DOI 10.1038/s41467-024-46737-3
View details for PubMedID 38538594
View details for PubMedCentralID PMC10973386
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Selective loss of primary cilia and neurotrophic signaling in G51D α-synuclein mice highlights a common pathway to Parkinson's disease.
Proceedings of the National Academy of Sciences of the United States of America
2026; 123 (33): e2619797123
Abstract
Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of α-synuclein aggregates in the brain. G51D α-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-α-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrophic signaling needed to sustain dopaminergic neurons. We show here that G51D α-synuclein mice share these phenotypes. Phospho-Ser129 α-synuclein accumulation correlates with cilia loss in cholinergic interneurons but not in spiny projection neurons that accumulate higher phospho-α-synuclein levels. In the piriform cortex, parvalbumin neurons lose primary cilia and downregulate Neurturin, potentially contributing to olfactory dysfunction. Within the peripheral olfactory epithelium, horizontal basal cells lose cilia, whereas multiciliated olfactory sensory neuron cilia remain intact. These findings reveal convergent cellular vulnerabilities across Parkinson's disease models and highlight a pathogenic role for impaired ciliary signaling.
View details for DOI 10.1073/pnas.2619797123
View details for PubMedID 42574603
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Airway Cells 3D Reconstruction via Manual and Machine-Learning Aided Segmentation of Volume EM Datasets.
Methods in molecular biology (Clifton, N.J.)
2024; 2725: 131-146
Abstract
Volume electron microscopy (vEM) is a high-resolution imaging technique capable of revealing the 3D structure of cells, tissues, and model organisms. This imaging modality is gaining prominence due to its ability to provide a comprehensive view of cells at the nanometer scale. The visualization and quantitative analysis of individual subcellular structures however requires segmentation of each 2D electron micrograph slice of the 3D vEM dataset; this process is extremely laborious de facto limiting its applications and throughput. To address these limitations, deep learning approaches have been recently developed including Empanada-Napari plugin, an open-source tool for automated segmentation based on a Panoptic-DeepLab (PDL) architecture. In this chapter, we provide a step-by-step protocol describing the process of manual segmentation using 3dMOD within the IMOD package and the process of automated segmentation using Empanada-Napari plugins for the 3D reconstruction of airway cellular structures.
View details for DOI 10.1007/978-1-0716-3507-0_8
View details for PubMedID 37856022
View details for PubMedCentralID 7954287
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ARL13B controls male reproductive tract physiology through primary and Motile Cilia.
Communications biology
2024; 7 (1): 1318
Abstract
ARL13B is a small regulatory GTPase that controls ciliary membrane composition in both motile cilia and non-motile primary cilia. In this study, we investigated the role of ARL13B in the efferent ductules, tubules of the male reproductive tract essential to male fertility in which primary and motile cilia co-exist. We used a genetically engineered mouse model to delete Arl13b in efferent ductule epithelial cells, resulting in compromised primary and motile cilia architecture and functions. This deletion led to disturbances in reabsorptive/secretory processes and triggered an inflammatory response. The observed male reproductive phenotype showed significant variability linked to partial infertility, highlighting the importance of ARL13B in maintaining a proper physiological balance in these small ducts. These results emphasize the dual role of both motile and primary cilia functions in regulating efferent duct homeostasis, offering deeper insights into how cilia related diseases affect the male reproductive system.
View details for DOI 10.1038/s42003-024-07030-7
View details for PubMedID 39397107
View details for PubMedCentralID PMC11471856
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Phase-shift nanodroplets as an emerging sonoresponsive nanomaterial for imaging and drug delivery applications.
Nanoscale
2022; 14 (8): 2943-2965
Abstract
Nanodroplets - emerging phase-changing sonoresponsive materials - have attracted substantial attention in biomedical applications for both tumour imaging and therapeutic purposes due to their unique response to ultrasound. As ultrasound is applied at different frequencies and powers, nanodroplets have been shown to cavitate by the process of acoustic droplet vapourisation (ADV), causing the development of mechanical forces which promote sonoporation through cellular membranes. This allows drugs to be delivered efficiently into deeper tissues where tumours are located. Recent reviews on nanodroplets are mostly focused on the mechanism of cavitation and their applications in biomedical fields. However, the chemistry of the nanodroplet components has not been discussed or reviewed yet. In this review, the commonly used materials and preparation methods of nanodroplets are summarised. More importantly, this review provides examples of variable chemistry components in nanodroplets which link them to their efficiency as ultrasound-multimodal imaging agents to image and monitor drug delivery. Finally, the drawbacks of current research, future development, and future direction of nanodroplets are discussed.
View details for DOI 10.1039/d1nr07882h
View details for PubMedID 35166273