Contact

  • Academic
    slozanov@stanford.edu
    University - Student Department: School of Medicine - IDP's - Neurosciences Position: Graduate

All Publications

  • Noncoding RNAs orchestrating the central dogma. The Journal of biological chemistry Lozano-Villada, S., Puthanveettil, S. V. 2026; 302 (1): 110933

    Abstract

    Once considered mere transcriptional noise, noncoding RNAs (ncRNAs) are now recognized as central players in cellular function-serving as scaffolds, catalysts, and regulators of gene expression. Their pervasive influence compelled a fundamental reevaluation of the central dogma of molecular biology, which traditionally emphasized the linear flow of genetic information from DNA to RNA to protein. In this review, we highlight critical roles played by ncRNAs and the outstanding challenges in decoding their mechanisms of action. We focus in particular on the emergent view that ncRNAs operate as components of highly integrated and dynamic regulatory networks. These RNA interactomes are governed by precise spatiotemporal constraints yet remain flexible enough to adapt to shifting cellular demands. Key questions remain about how such networks are prioritized, regulated, and dynamically reshaped in response to physiological signals. To contextualize these mechanisms, we spotlight the nervous system, a tissue enriched in regulatory RNAs, as a model for understanding how ncRNA-mediated regulation contributes to cellular specialization and plasticity. Unraveling the principles governing ncRNA interactions will reveal new dimensions of the genetic code, one that is not simply read but interpreted and orchestrated by RNA.

    View details for DOI 10.1016/j.jbc.2025.110933

    View details for PubMedID 41242393

    View details for PubMedCentralID PMC12753233

  • PKA orchestrates long-range lysosomal vesicle transport during synaptic maintenance. iScience Badal, K. K., Zhao, Y., Raveendra, B. L., Lozano-Villada, S., Miller, K. E., Puthanveettil, S. V. 2025; 28 (12): 113878

    Abstract

    Bidirectional long-distance transport of organelles is crucial for communication between the cell body and synapses, yet how this transport is regulated during synapse formation, maintenance, and plasticity remains unclear. In the Aplysia sensory neuron (SN)-motor neuron system, which mediates the gill-siphon withdrawal reflex, we demonstrate that synapse maintenance coincides with a sustained decrease in retrograde lysosomal vesicle (LV) transport in SNs. This reduction becomes evident three days after synapse formation, in contrast to anterograde mitochondrial transport, which increases within 12 h. Serotonin-induced, learning-related synapse formation further suppresses retrograde lysosomal transport within 24 h, while boosting anterograde mitochondrial transport as early as 1 h post-exposure. A pharmacological screen implicates PKA as a key regulator of retrograde LV transport during synapse maintenance. These results reveal organelle-specific, temporally distinct regulation of long-distance transport in synapse formation, maintenance, and plasticity.

    View details for DOI 10.1016/j.isci.2025.113878

    View details for PubMedID 41399515

    View details for PubMedCentralID PMC12702187

  • lncRNA ADEPTR loss-of-function elicits sex-specific behavioral and spine deficits. iScience Chanda, K., Carter, J. P., Nishizono, H., Raveendra, B. L., Brantley, A., Grinman, E., Espadas, I., Lozano-Villada, S., Wingfield, J. L., Wagner, G., Peterson, A., Yasuda, R., Puthanveettil, S. V. 2025; 28 (8): 113070

    Abstract

    Activity-dependent neuronal changes are critical for learning and memory, but the role of long noncoding RNAs (lncRNAs) in these processes is under active investigation. In this study we investigated ADEPTR, a dendritically localized, cAMP-modulated lncRNA essential for synapse morphology. Using two mouse models-one with ADEPTR deletion (L-ADEPTR) and another lacking its protein interaction domain (S-ADEPTR)-we examined sex-specific effects on behavior and neuronal architecture. Behavioral tests showed reduced anxiety in S-ADEPTR adult male mice, with no learning or memory deficits in either model. Neuronal cultures and brain samples from various developmental stages revealed morphological impairments in both sexes. Notably, L-ADEPTR female mice had fewer thin spines in the hippocampal CA1 region at postnatal day 42. Despite these structural deficits, increased expression of plasticity-related genes BDNF and cFOS in the cortex and hippocampus suggests compensatory mechanisms preserve cognitive function. These findings highlight a sex-specific role for ADEPTR in regulating neuronal structure and anxiety-related behaviors.

    View details for DOI 10.1016/j.isci.2025.113070

    View details for PubMedID 40740495

    View details for PubMedCentralID PMC12307743

  • Single-neuron analysis of aging-associated changes in learning reveals impairments in transcriptional plasticity. Aging cell Badal, K. K., Sadhu, A., Raveendra, B. L., McCracken, C., Lozano-Villada, S., Shetty, A. C., Gillette, P., Zhao, Y., Stommes, D., Fieber, L. A., Schmale, M. C., Mahurkar, A., Hawkins, R. D., Puthanveettil, S. V. 2024; 23 (9): e14228

    Abstract

    The molecular mechanisms underlying age-related declines in learning and long-term memory are still not fully understood. To address this gap, our study focused on investigating the transcriptional landscape of a singularly identified motor neuron L7 in Aplysia, which is pivotal in a specific type of nonassociative learning known as sensitization of the siphon-withdraw reflex. Employing total RNAseq analysis on a single isolated L7 motor neuron after short-term or long-term sensitization (LTS) training of Aplysia at 8, 10, and 12 months (representing mature, late mature, and senescent stages), we uncovered aberrant changes in transcriptional plasticity during the aging process. Our findings specifically highlight changes in the expression of messenger RNAs (mRNAs) that encode transcription factors, translation regulators, RNA methylation participants, and contributors to cytoskeletal rearrangements during learning and long noncoding RNAs (lncRNAs). Furthermore, our comparative gene expression analysis identified distinct transcriptional alterations in two other neurons, namely the motor neuron L11 and the giant cholinergic neuron R2, whose roles in LTS are not yet fully elucidated. Taken together, our analyses underscore cell type-specific impairments in the expression of key components related to learning and memory within the transcriptome as organisms age, shedding light on the complex molecular mechanisms driving cognitive decline during aging.

    View details for DOI 10.1111/acel.14228

    View details for PubMedID 38924663

    View details for PubMedCentralID PMC11488329